Tissue Acquisition for Analysis of Prognostic Factors, Immunology, and Genetic Progression of HIV-1 Associated Malignancies
Conditions: Lung Cancer, Lymphoma
Sponsor: AIDS Malignancy Consortium

 
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AIDS MALIGNANCY CONSORTIUM 
 
 
 
AMC PROTOCOL #083: 
Tissue Acquisition for Analysis of Prognostic Factors, 
Immunology, and Genetic Progression of HIV-1 Associated 
Malignancies  
A Trial of the AIDS Malignancy Consortium (AMC) 
 
 
Sponsored by: 
National Cancer Institute 
Office of HIV and AIDS Malignancies 
 
Collaborator: 
Office of Cancer Genomics 
 
NCT Registration 
Number: 
NCT01567722 
 
Protocol Chair: 
Lee Ratner, M.D., Ph.D. (IVR-25383) 
 
Protocol Co-chair: 
Richard Ambinder, M.D., Ph.D. (IVR-10686) 
Ariela Noy, M.D. (IVR-28244) 
Dirk Dittmer, Ph.D. (NPIVR-44410) 
 
Version 7.0 
NCI Version Date: 25NOV2020 
 

 
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AMC PROTOCOL SIGNATURE PAGE 
 
I, ________________________________, Principal Investigator at site _______, agree to conduct 
and follow this protocol: AMC Protocol #083: Tissue Acquisition for Analysis of Prognostic 
Factors, Immunology, and Genetic Progression of HIV-1 Associated Malignancies (Version 
7.0; 25NOV2020), as written according to AMC, NCI, and FDA guidelines. In accordance with 
NCI policy, I understand that no deviations from the protocol enrollment criteria or waivers for 
protocol deviations are permitted. 
 
 
_________________________________ 
_____________________ 
 
Signature 
Date (DDMMMYYYY) 

 
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TABLE OF CONTENTS 
SUMMARY OF CHANGES ......................................................................................................... i 
I. 
Scientific and Substantive Changes: .......................................................................... i 
II. 
Administrative and Editorial Changes: ..................................................................... i 
AMC PROTOCOL SIGNATURE PAGE .................................................................................. 2 
TABLE OF CONTENTS ............................................................................................................. 3 
PROTOCOL SYNOPSIS ............................................................................................................. 6 
PROTOCOL SCHEMA ............................................................................................................... 8 
1.0 BACKGROUND ................................................................................................................ 10 
1.1 HIV-Associated Malignancies .................................................................................. 10 
1.2 Rationale .................................................................................................................... 11 
2.0 OBJECTIVE ...................................................................................................................... 13 
3.0 ELIGIBILITY CRITERIA ............................................................................................... 14 
3.1 Inclusion Criteria ...................................................................................................... 14 
3.2 Exclusion Criteria ..................................................................................................... 15 
3.3 Accrual Targets ......................................................................................................... 15 
4.0 DATA ENTRY ................................................................................................................... 16 
4.1 Participant Enrollment Procedures ........................................................................ 16 
4.2 On-Study Data Entry Procedures ........................................................................... 17 
5.0 SAMPLE ACQUISITION AND PROCESSING ............................................................ 18 
5.1 Sample Acquisition ................................................................................................... 18 
5.2 Sample Storage .......................................................................................................... 19 
5.3 Biopsies Negative for Malignancy ........................................................................... 20 
5.4 Sample Analysis ........................................................................................................ 20 
6.0 CLINICAL INFORMATION AND MAINTENANCE OF AN HIV-MALIGNANCY 
DATABASE ........................................................................................................................ 22 
6.1 Data Collection .......................................................................................................... 22 
6.2 Duration of Follow-up Data Collection ................................................................... 22 
6.3 Recording Information in the Database ................................................................. 23 
7.0 DISTRIBUTION OF SAMPLES TO RESEARCHERS ................................................ 24 
8.0 POTENTIAL RISKS ......................................................................................................... 25 
8.1 Risks of Tumor or Node Biopsy ............................................................................... 25 

 
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8.2 Risks of Blood Collection ......................................................................................... 25 
8.3 Breach of Confidentiality ......................................................................................... 25 
9.0 STATISTICAL CONSIDERATIONS ............................................................................. 26 
10.0 ROLE OF DATA MANAGEMENT ................................................................................ 27 
10.1 CRF Instructions ....................................................................................................... 27 
10.2 Data Quality .............................................................................................................. 27 
10.3 Data Monitoring ........................................................................................................ 27 
11.0 ETHICAL CONSIDERATIONS ...................................................................................... 28 
11.1 Informed Consent ..................................................................................................... 28 
11.2 Changes to the Protocol ............................................................................................ 30 
11.3 Women and Minorities ............................................................................................. 30 
11.4 Confidentiality ........................................................................................................... 30 
12.0 REFERENCES ................................................................................................................... 32 
APPENDIX I: AMC DATA AND SAFETY MONITORING PLAN .................................... 33 
APPENDIX III: PROCESSING BLOOD SAMPLES FOR THE HIV+ TUMOR 
MOLECULAR CHARACTERIZATION PROJECT ................................................... 40 
APPENDIX IV: SHIPPING INSTRUCTIONS FOR SUBMITTING PBMC, SNAP 
FROZEN BIOPSY TISSUE, AND FORMALIN-FIXED TISSUE TO THE AMC 
BIOREPOSITORY ............................................................................................................ 43 
APPENDIX V: PERFORMANCE STATUS SCALES ........................................................... 47 
 
 

 
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PROTOCOL ROSTER 
Tissue Acquisition for Analysis of Prognostic Factors, Immunology, and Genetic 
Progression of HIV-1 Associated Malignancies 
 
Protocol Chair: 
Lee Ratner, M.D., Ph.D. 
Washington University School of Medicine 
Division of Oncology 
660 S. Euclid Ave., Campus Box 8069 
St. Louis, MO 63110 
Tel: 314-362-8836 
Fax: 314-747-2120 
Email: lratner@dom.wustl.edu 
Collaborator: 
Nicholas Griner, Ph.D. 
Scientific Program Manager 
Office of Cancer Genomics 
National Cancer Institute 
Tel: 978-796-5277 
Fax: 301-480-4368 
Email: nicholas.griner@nih.gov 
Protocol Co-Chairs: 
Richard F. Ambinder M.D., Ph.D. 
Johns Hopkins School of Medicine 
1650 Orleans Street 
CRB1, Room 389 
Baltimore, MD 21287 
Tel: 410-955-8839 
Fax 410-955-0960 
Email: ambinri@jhmi.edu  
 
Dirk Dittmer, Ph.D. 
Vironomics Core 
450 West Dr. Rm 12-056 
CB#7295 
Chapel Hill, NC 27599 
Tel: 919-260-1695 
Fax: 919-962-8103 
Email: ddittmer@med.unc.edu 
 
Ariela Noy, M.D. 
Memorial Sloan-Kettering Malignancy Center 
Lymphoma Service 
1275 York Avenue 
New York, NY 10065 
Tel: 212-639-7423 
Fax: 646-422-2284 
Email: noya@mskcc.org 
Statistician: 
Jeannette Lee, Ph.D. 
University of Arkansas for Medical Sciences 
College of Public Health, Biostatistics 
4301 W Markham St, Slot 781; Room 3212 
Little Rock, AR 72205-7199 
Tel: (501) 526-6712 
Fax: (501) 526-6729 
Email: JYLee@uams.edu 
 
Data Management/Operations: 
AMC Operations and Data Management Center 
The Emmes Company, LLC 
401 N. Washington Street, Suite 700 
Rockville, MD 20850 
Tel: 301-251-1161 
Fax: 240-238-2842 
Email: amcpm@emmes.com 
 
AMC Biorepository: 
Sylvia Silver, D.A. 
George Washington University Medical Center 
Ross Hall, Room 118 
2300 I Street NW 
Washington, DC 20037 
Tel: 202-994-2945 
Fax: 202-994-5056 
Email: ssilver@email.gwu.edu, amc-
bio@emmes.com 

 
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PROTOCOL SYNOPSIS 
 
TITLE: 
Tissue Acquisition for Analysis of Prognostic Factors, Immunology, 
and Genetic Progression of HIV-1 Associated Malignancies (AMC-
083) 
ACCRUAL TARGET: 
Up to 200 participants will be enrolled (up to 100 participants with 
each of the malignancies eligible for participation). 
PHASE OF STUDY: 
Observational (biospecimen banking and genetic sequencing) 
PARTICIPATING SITES: 
 
This protocol is open to all AMC member institutions in the U.S. and 
Latin America. 
POPULATION: 
 
HIV-positive persons age 18 and older with a diagnosis of a 
malignancy limited to the following diagnoses: diffuse large B cell 
lymphoma (DLBCL) or non-small cell lung malignancy. 
REGIMEN: 
Specimen and data collection at the time of diagnosis and prior to 
treatment initiation, and data collection at 1 and 2 years after 
diagnosis. Archival specimens from deceased participants or from 
participants who are unreachable for informed consent are permitted 
(with institutional review board [IRB] approval for a waiver of 
informed consent). Required study specimens include a snap frozen 
tumor tissue biopsy of minimum size 10 x 10 x 2 mm (approximately 
100 
mg) 
OR 
formalin-fixed, 
paraffin-embedded 
(FFPE) 
(approximately 10-20 mg) tumor tissue biopsy that is sufficiently 
large to enable extraction of nucleic acids needed for the study, AND 
separate slides of diagnostic biopsies or other representative tissue for 
central pathology review. A whole blood sample will be collected and 
processed for PBMC (this requirement is waived for deceased 
participants and live participants who are unreachable to provide 
consent or a blood specimen). If the tissue source site cannot release 
a FFPE block for sequencing purposes, tissue scrolls and molecular 
QC slides will be required and cut according to Appendix IV. 
Specimens will be banked at the AMC Biorepository at George 
Washington University, which will serve as a Tissue Source Site 
(TSS) for all AMC sites, for future testing at the Genome Science 
Center of British Columbia (GSC-BC) for the HIV+ Tumor 
Molecular Characterization Project (HTMCP). 
DURATION: 
Initial specimen and data collection will occur at the time of 
malignancy diagnosis, prior to treatment initiation. Participants will 
be followed for up to 2 years after diagnosis to report on clinical 
outcomes. Archival cases qualifying for a waiver of consent may be 
submitted with the available follow-up data relative to the diagnosis 
date for the malignancy. 

 
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PRIMARY OBJECTIVE: 
To obtain high quality, clinically annotated tissue from participant 
with HIV-1 malignancy. This material will be used to study clinical, 
genetic, and immunologic parameters, which have prognostic 
significance and/or are involved in the initiation and progression of 
HIV-1 malignancies in the context of the HTMCP initiative. This 
will include complete genomic sequence determination of HIV-
associated diffuse large B cell lymphomas and non-small cell lung 
cancer. 

 
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PROTOCOL SCHEMA 
 
Eligible Participants 
Clinical diagnosis of HIV infection and the presence of one of the following two previously 
untreated malignancies: 
• Diffuse Large B Cell Lymphoma (DLBCL) (plasmablastic lymphoma and primary effusion 
lymphoma cases are permitted) 
• Non-Small Cell Lung Malignancy 
Procedures 
Collection required prior to treatment initiation (or for deceased participants, at the time of case 
identification): 
• Tumor tissue biopsy for genomic sequencing 
o Snap frozen tissue sample (minimum size of 10 x 10 x 2 mm, approx. 100 mg) 
OR 
o Formalin-fixed, paraffin-embedded (FFPE) tissue block, or tissue scrolls and molecular 
QC H&E slides if the site cannot release the tissue block (minimum size approximately 10-
20 mg. Fixative buffer pH and age of FFPE sample should be noted) 
Note: Tumor cases without a normal tissue sample and sample types not specified above 
can still be accepted with written permission from the Office of Cancer Genomic (OCG), 
and will be included as validation samples. 
• FFPE diagnostic tissue block or unstained slides from the block for pathology review* 
• Blood for normal Peripheral Blood Mononuclear Cells (PBMC), if available** 
• Data collection for enrollment and medical history 
1 and 2 years after enrollment: 
• Data collection for clinical outcomes 
Specimen and Data Submission 
• AMC sites enroll potential participants in AdvantageEDCSM following consent or 
identification of an archival case (if local requirements for a waiver of consent are met).  
• AMC sites ship tissue for genomic sequencing, FFPE tissue for pathology review, and PBMC 
(if available) to the AMC Biorepository. The AMC ODMC, AMC Biorepository, and OCG 
will work with AMC sites to coordinate the creation of slides (for QC prior to extraction) and 
adjacent tissue scrolls for nucleic acid extraction for cases that have passed central pathology 
if the site cannot release the tissue block for processing by the HTMCP. The AMC 
Biorepository will transfer the materials to the AIDS and Cancer Specimen Resource (ACSR) 
for distribution to the HIV Tumor Malignancy Characterization Project (HTMCP). 
• The ACSR will: 

 
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o Cut unstained slides from the FFPE tissue block for Central Pathology purposes (4 slides 
for lung tissue or 12 slides for DLBCL), and submit slides to the appropriate Pathology 
Review Committee for the malignancy type per HTMCP SOPs. Tissue blocks will be 
returned to sites. 
o Batch and ship blood and frozen tissue samples to the GSC-BC. 
o If an FFPE tissue block is submitted for sequencing instead of frozen tumor tissue, slides 
will be cut for molecular QC as well as tissue scrolls per Appendix IV. 
• AMC sites enroll cases that pass central pathology review in AdvantageEDCSM. Archival cases 
may be submitted with available follow-up data (1 and 2 years post diagnosis) relating to 
clinical outcomes within 4 weeks after case acceptance.  
• AMC sites will submit required data elements in the HTMCP clinical report forms via upload 
to the AdvantageEDC Internet Data Entry System within 4 weeks of data collection time points 
at study entry and 1 and 2 years after diagnosis. 
* If the diagnostic tissue block is not available, another representative FFPE tissue block that 
was collected from an area near the location of the diagnostic biopsy may be submitted for 
pathology review. The AMC Biorepository will return all tissue blocks to the site after cutting 
slides for pathology review. The site may submit formalin-fixed, unstained slides for all 
malignancy types only if the institution will not release a tissue block (4 for lung tissue or 12 
for DLBCL tissue). 
**  Blood samples from live participants may be collected after treatment initiation if necessary. 
This requirement is waived for deceased participants or from participants with archival tissue 
who are unreachable for informed consent and a fresh blood sample collection. 

 
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1.0 
BACKGROUND 
1.1 
HIV-Associated Malignancies 
HIV infection is associated with a variety of malignancies, including “AIDS-defining 
cancers” and “non-AIDS-defining cancers” [1]. The AIDS-defining cancers include non-
Hodgkin’s lymphoma, Kaposi’s sarcoma, and cervical cancer. AIDS-defining non-
Hodgkin’s lymphomas are predominantly diffuse B-cell lymphomas, Burkitt’s 
lymphomas, and less commonly, primary effusion lymphomas and plasmablastic 
lymphomas. Non-AIDS defining cancers that are increased in prevalence among HIV-1 
infected individuals include anal carcinomas, Hodgkin’s lymphomas, non-small cell lung 
cancers, and hepatocellular carcinomas. 
There are multiple mechanisms to account for the increased prevalence of malignancies in 
HIV-1 infected individuals, but these processes have been incompletely characterized in 
molecular detail. Many HIV-associated malignancies are associated with other oncogenic 
virus infections. These include members of the human papillomavirus and gamma 
herpesvirus families, including Epstein-Barr virus and Kaposi’s sarcoma herpes virus 
(KSHV). These infections may be pathogenic in immunosuppressed individuals as a result 
of an impaired cell-mediated immune response, resulting in chronic and incompletely 
suppressed infection. Malignancies may also arise from cytokine release from activated T 
cells induced by HIV infection or other opportunistic infectious agents complicating HIV 
infection. 
Viruses are associated with a variety of malignancy and pre-malignant conditions [2]. 
Human papillomaviruses are the cause of almost all anogenital carcinomas and 
approximately 50% of oral malignancies [3, 4]. Epstein-Barr virus is associated with 
Burkitt’s lymphoma, nasopharyngeal and gastric carcinomas, NK/T cell lymphomas, AIDS 
lymphomas, Hodgkin’s lymphomas, post-transplant lymphoma, and pediatric AIDS-
associated leiomyosarcomas [5]. KSHV (human herpes virus 8, HHV8) is associated with 
Kaposi’s sarcoma, primary effusion lymphomas, and multicentric Castleman’s disease [6]. 
Human T-cell leukemia virus (HTLV) type 1 causes adult T-cell leukemia and HTLV-
associated myelopathy, as well as pneumopathy, uveitis, and immunosuppressive 
conditions [7]. A recently discovered polyoma virus, Merkel’s carcinoma virus, is 
associated with the majority of cases of Merkel’s neuroendocrine skin malignancies. 
Hepatitis viruses type B (HBV) and C (HCV) are associated with hepatocellular carcinoma, 
and HCV is also associated with splenic marginal zone lymphomas. Another recently 
identified virus, xenotropic murine leukemia-related virus (XMRV) may be associated 
with human prostate malignancy and chronic fatigue syndrome, although this remains 
controversial [8]. Other viruses have been implicated in collagen vascular, hepatobiliary, 
and other malignancies, but definitive information is currently lacking [9, 10]. 
HIV-1 and -2 are associated with immunodeficiency, which predisposes individuals to 
infections by opportunistic infectious agents, including oncogenic viruses. HIV-associated 
immunodeficiency also inhibits anti-tumor mechanisms that result in an increased 
frequency of a variety of tumors [11, 12]. Thus, HIV-1 infection is associated with 
markedly increased prevalence in AIDS-defining malignancies, such as Kaposi’s sarcoma, 
non-Hodgkin’s lymphoma, and cervical malignancies, and increased prevalence of non-

 
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AIDS defining malignancies, including: Hodgkin’s lymphoma, anal carcinomas, plasma 
cell neoplasms, and hepatocellular, lung, and testicular malignancies. The effects of HIV 
and other viruses on mechanisms of tumorigenesis remain to be defined, and this 
information may provide a solid foundation for new therapeutic approaches. 
Comprehensive sequencing of genomes and transcriptomes in cancers that arise in HIV-
infected individuals through the HIV+ Tumor Molecular Characterization Project 
(HTMCP, http://cgap.nci.nih.gov/Cancer_Types) may provide a starting point for a 
systems biology approach towards understanding differences in pathway activation among 
identical histological subtypes of cancers in immunocompetent and immunodeficient 
patients. The results obtained should provide important clues to the pathways that either 
allow tumors to counteract immune surveillance mechanisms or are redundant in the 
presence of an extrinsic oncogenic influence such as oncogenic viruses. 
1.2 
Rationale 
Rapidly evolving sequencing and informatics tools are substantially diminishing costs of 
comprehensive characterization of tumor transcriptomes and tumor genomes. These 
advances have resulted in detailed information on the repertoire of alterations in cancers. 
Novel approaches of genomic sequencing analyses have provided new tools of pathogens 
discovery and new information on cellular genetic alterations associated with viral 
pathogenesis. 
The availability of high quality, clinically annotated participant samples is crucial for the 
study of biologic factors, which influence the progression and treatment response of HIV-
1 malignancies. Comprehensive genomic sequences of HIV-associated cancers may 
identify diagnostic or prognostic disease signatures, and recurrent “driver” alterations that 
may be targets for new therapies. It is also possible that the comparison of transcriptomes 
and genomes between lymphomas from HIV+ and HIV- individuals might identify novel 
non-human sequences that could potentially suggest the presence of transcripts from 
hitherto undiscovered oncogenic viral agents. 
The National Cancer Institute’s Office of Cancer Genomics (OCG) and the Office of HIV 
and AIDS Malignancy (OHAM) have developed an initiative to compare the cancer related 
alterations in HIV+ participants and HIV- participants. It is possible that the comparison 
of transcriptomes and genomes between tumors from HIV+ and HIV- individuals may or 
may not identify novel non-human sequences, which could suggest the presence of 
transcripts from known or hitherto undiscovered oncogenic viral agents. This protocol 
serves to collect specimens for banking at the AMC Biorepository, for future testing at the 
Genome Science Center of British Columbia (GSC-BC) for the HIV+ Tumor Molecular 
Characterization Project (HTMCP). 
The current study will investigate genomic sequences in two different HIV-1-associated 
malignancies: diffuse large B cell lymphoma and lung cancer. Lymphoma was chosen as 
an AIDS-defining malignancy that occurs more frequently in HIV-positive individuals 
compared to HIV-negative individuals [13,14]. However, only diffuse large B cell 
lymphoma (including plasmablastic lymphoma [PBL] and primary effusion lymphoma 
[PEL]) will be included in this study, as Burkitt lymphoma is studied independently in 

 
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another protocol, and occurs with a lower frequency. Two other malignancy types, anal 
cancer and cervical cancer, were initially included in this protocol: enrollment of anal 
cancer cases was discontinued with protocol version 4.0 due to the rarity of identifying 
tumor tissue samples of sufficient size for this protocol’s tissue requirements, and 
enrollment of cervical cancer cases was discontinued with protocol version 6.0 due to 
overall HTMCP accrual completion for these cases. Lung cancer and diffuse large B cell 
lymphoma were chosen for comparison to full genomic sequence data that has been 
obtained for the corresponding malignancies in HIV-negative individuals to determine if 
there are differences in the pathogenesis of these disorders in the HIV-1-positive versus 
HIV-1-negative participants [15, 16, 17]. 

 
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2.0 
OBJECTIVE 
The primary objective of this project is to obtain high quality, clinically annotated tissue 
from participants with HIV-1 malignancy. This material will be used to study clinical, 
genetic, and immunologic parameters, which have prognostic significance and/or are 
involved in the initiation and progression of HIV-1 malignancies in the context of the 
HTMCP initiative. This will include complete genomic sequence determination of HIV-
associated diffuse large B cell lymphomas and lung cancer. 

 
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3.0 
ELIGIBILITY CRITERIA 
A rostered AMC investigator must document that each protocol participant meets all stated 
eligibility criteria. Participating sites must have documentation that each eligibility 
requirement is satisfied prior to participant enrollment. In compliance with CTEP policy, 
no exceptions to eligibility criteria will be granted under any circumstance. 
NOTE: Institutions may use this section of the protocol as an eligibility checklist for source 
documentation if it has been reviewed, signed, and dated before registration/randomization 
by the study investigator. If used as source documentation, this checklist must be printed, 
the investigator must check each item to document their assessment that the participant 
meets each eligibility criterion, and the completed checklist must be maintained in the 
participant’s chart. 
Participant ID Number: 083 - ___ ___ ___ - ___ ___ ___ 
Patient’s Initials (L, F, M (optional)): ___ ___ ___ 
NOTE: All questions regarding eligibility should be directed to the study chair. 
3.1 
Inclusion Criteria 
3.1.1 Malignancy diagnosis. Participants must have a diagnosis of HIV-associated 
malignancy of one of two types: 
• All variants of Diffuse Large B Cell Lymphoma (except Burkitt’s lymphoma). 
• Non-Small Cell Lung Malignancy 
3.1.2 Previous chemotherapy: tumors will be accepted that have had previous 
neoadjuvant/chemotherapy treatment, but the specific treatment regimen must be 
noted and communicated to the OCG. 
3.1.3 Previous malignancies: tumors from participants with previous malignancies will 
be accepted, but any previous malignancies must be noted and communicated to 
the OCG. 
3.1.4 HIV diagnosis. HIV infection based on serologic documentation of HIV infection 
at any time prior to study entry, as evidenced by positive ELISA, positive Western 
Blot, or any other FDA-approved (licensed) HIV test. Alternatively, this 
documentation may include a record that another physician has documented that 
the participant has HIV based on prior ELISA and western blot, or other approved 
diagnostic tests. 
3.1.5 Age. Participants must be ≥ 18 years old, in order to focus on adult oncology 
participants and in light of differences in tumor mutational spectrum that are likely 
to be found in pediatric compared to adult tumors. 
3.1.6 Informed Consent. Unless the IRB of record has granted a waiver of the 
requirement to obtain informed consent from participants with archival specimens 
who cannot be contacted or the participant is deceased, participants must be willing 
and able to sign an IRB-approved informed consent document that permits the use 
of samples for genomic-based molecular characterization projects.  

 
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3.1.7 Complete Case Requirements. The site must ensure the minimum specimen 
requirements for HTMCP case submission can be met, including the availability 
of/ability to collect: 
• Tumor tissue for genomic analysis that was collected prior to initiating 
treatment for the malignancy (preferable). Repeat tumor biopsy will not be 
performed solely to meet the protocol specimen collection requirements. 
Acceptable tissue includes: 
o Flash-frozen diagnostic tumor biopsy tissue (minimum specimen size of 10 
x 10 x 2 mm, approximately 100 mg). 
o FFPE tumor biopsy material tissue, which may include a tissue block OR 
tissue scrolls and slides for molecular QC (see Appendix IV) if a block is 
not released. 
o Tumor tissue sample with specifications other than those noted above for 
which the Office of Cancer Genomics (OCG) has provided written approval 
for submission to project.Tumor cases without a normal tissue sample can 
still be accepted with written permission from OCG, and will be included 
as validation samples. 
• A 10 ml blood specimen for PBMC isolation. For live participants, blood 
samples should be collected prior to treatment initiation for the malignancy if 
possible, but may be collected after treatment initiation if necessary. This 
requirement is waived for deceased participants or live participants who are 
unavailable to provide a whole blood sample. 
• Diagnostic FFPE tissue block for central pathology review. If the diagnostic 
tissue block is not available, another representative FFPE tissue block that was 
collected from an area near the location of the diagnostic biopsy may be 
submitted for pathology review. The site may submit formalin-fixed, unstained 
slides for all malignancy types only if the institution will not release a tissue 
block (4 slides for lung tissue or 12 slides for DLBCL tissue). 
• Completed HTMCP enrollment form for the applicable tumor type. 
3.2 
Exclusion Criteria 
Participants who do not fulfill the criteria as listed in Section 3.1 above, are ineligible. 
Additionally, the presence of any of the following conditions will exclude a participant 
from study enrollment: 
3.2.1 Participant can be contacted but is unwilling or unable to provide informed 
consent.3.3 
Accrual Targets 
3.3.1 Number of participants to be enrolled: Up to 200 participants will be enrolled, 
including up to 100 participants with each of the 2 eligible malignancies. 
3.3.2 Accrual rate: The anticipated accrual period is 8 years or more (accrual rate of 6 
participants per month). 

 
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4.0 
DATA ENTRY 
4.1 
Participant Enrollment Procedures 
4.1.1 Institutional requirements for enrollment: Sites must have this protocol approved 
by their Institutional Review Boards (IRB) and be registered for study participation 
with the AMC Operations and Data Management Center (ODMC) before they may 
enroll participants. Additionally, participating institutions must submit a completed 
Institutional Certification for the submission of study data to the NIH Database of 
Genotypes and Phenotypes (dbGaP) before transmitting samples or data for this 
project. A template institutional certification letter is provided among the protocol-
specific materials for this project at www.AIDSCancer.org and in OCG Template 
#105, Institutional Certification for Participation in Office of Cancer Genomics 
Policy, 
available 
online 
at: 
https://ocg.cancer.gov/sites/default/files/HTMCP_SOP_manual.pdf. 
4.1.2 Screening enrollment and sample collection 
After obtaining informed consent from a potential participant (or for deceased or 
archival cases from unreachable participants, identifying an eligible case), the site 
will collect tumor tissue and records to confirm the participant’s diagnosis and 
determine eligibility. AMC sites will initiate case submission by registering the 
participant via the AMC AdvantageEDC Internet Data Entry System. The 
participating site will ensure the participant meets all eligibility criteria prior to 
completing the protocol-specific eligibility checklist in AdvantageEDC (Segment 
A registration). 
Both GlobalTraceSM and HTMCP specimen ID labels will be used for tracking 
specimens prior to acceptance by the HTMCP. All sites will be provided 
GlobalTrace labels for use in submitting specimens for eligibility review. The AMC 
Biorepository will be provided pre-printed HTMCP specimen ID labels to affix to 
submitted specimens before shipping to the appropriate laboratory. Only HTMCP 
specimen IDs will be tracked by OCG once the case is accepted for genomic 
sequencing. 
Participating sites will collect data in the applicable enrollment form for the 
malignancy type in the HTMCP’s paper forms, which are available among the 
protocol-specific materials for this project at www.AIDSCancer.org and will be 
attached to the enrollment notification for Segment A. The HTMCP Enrollment 
Form must be completed and uploaded in AdvantageEDC following Segment A 
registration for eligibility review by the project. Original copies of the HTMCP 
enrollment form must be maintained at the site. 
4.1.3 Specimen submission and eligibility review 
All required specimens must be submitted to the AMC Biorepository following 
registration in AdvantageEDC. Failure to submit any required specimens will result 
in case rejection. 
Once received at the AMC Biorepository, the AMC Biorepository will confirm that 

 
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all required specimens (e.g., tumor tissue for genomic sequencing, tumor tissue for 
pathology review, and/or PBMC) have been received, will prepare tissue sections 
or scrolls as necessary, prepare slides for central pathology review as required, and 
will distribute specimens for central pathology/case eligibility review. The AMC 
ODMC will provide enrollment information to OCG to review cases for inclusion 
in the project. OCG will communicate case acceptance to OCG’s designee 
(Nationwide Children’s Hospital [NCH]) and the AMC ODMC. 
4.1.4 HTMCP enrollment 
Following notification of case acceptance from OCG, the AMC ODMC will enroll 
the participant in Segment B of protocol AMC-083 in AdvantageEDC. The AMC 
ODMC will also enroll the participant in the HTMCP’s data entry system, 
maintained by NCH, using data provided in the Enrollment Form. 
4.2 
On-Study Data Entry Procedures 
Participating sites will collect data for the one and two years post diagnosis follow up time 
point in the Follow-up form for the applicable malignancy type in the HTMCP’s paper 
forms, which are available among the protocol-specific materials for this project at 
www.AIDSCancer.org. Completed HTMCP follow-up forms must be uploaded in the 
appropriate area of AdvantageEDC within 4 weeks before or after the target form 
submission deadline. For participants providing archived tissue specimens for genomic 
analysis, the Follow-up Form for the applicable malignancy type and duration since initial 
diagnosis will be due within 4 weeks of case acceptance. Original copies of the HTMCP 
Follow-up Forms must be maintained at the site. 

 
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5.0 
SAMPLE ACQUISITION AND PROCESSING 
5.1 
Sample Acquisition 
Samples will be obtained and processed using protocols developed for the HTMCP. These 
protocols can be found online at http://ocg.cancer.gov/resources/ocg-templates-and-
protocols. All samples will be obtained for the purposes of this study after the participant 
has provided informed consent. If the participant consents to provide previously collected 
tissue samples available from pathology for the baseline samples, a piece of the pathology 
specimen or the tissue block will be obtained for research purposes. Participants will not 
be re-biopsied solely for the purpose of sample collection. Retrospective cases may be 
submitted with the available follow-up data relative to the diagnosis date, if available. 
5.1.1 Tumor tissue biopsy 
All eligible participants will have biopsy tissue banked as part of this study. When 
clinically indicated, these participants will undergo biopsy of a lymph node or other 
organ involved with malignancy or a suspected malignancy. Biopsies must be 
surgical biopsies done in the operating room. After the necessary samples are 
obtained for the optimal medical care of the participant, a second tissue biopsy will 
be collected for the purposes of this protocol and submitted to the AMC 
Biorepository. The additional pieces of tissue must measure about 10 x 10 x 2 mm 
(approximately 100 mg per piece) (minimal amount of tissue required) and will be 
snap frozen within 20 minutes of the time tissue is removed from the participant. 
Do not freeze tissue pieces larger than this size or mass. The method of snap 
freezing and transport of frozen tissues is described in Appendix IV. The time 
between specimen collection and freezing must be recorded. 
If fresh frozen tissue is unavailable, a FFPE (approximately 10-20 mg)  tissue block 
may be submitted for genomic sequencing OR tissue scrolls if the site will not 
release the tissue block. Archival samples are permitted. Fixative buffer pH should 
be noted. If the FFPE tissue block is submitted for genomic analysis, the tissue 
block should be submitted to the AMC Biorepository for preparation of the tissue 
scrolls and molecular QC slides. The tissue block will be returned to the site after 
preparation of the slides. If the site will not release the tissue block to the AMC 
Biorepository after the case has passed central pathology review the AMC ODMC 
and OCG will work with the AMC site to adhere to the tissue scroll procedures 
described in Appendix IV. The site will be required to produce the necessary 
molecular QC H&E slides and tissue scrolls to be shipped to GSC-BC within 24 
hours of cutting scrolls. Alternatively, tumor tissue samples not meeting the 
specifications noted above may be submitted to the project ONLY with prior 
written approval from the Office of Cancer Genomics. Documentation of this 
approval must be provided to the AMC ODMC at the time of enrollment in 
AdvantageEDC. 
AMC sites will send additional tissue to the AMC Biorepository for pathology 
review (Appendix IV). If the diagnostic tissue block is not available, another 
representative FFPE tissue block that was collected from an area near the location 
of the diagnostic biopsy may be submitted for pathology review. The site may 

 
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submit formalin-fixed, unstained slides for all malignancy types only if the 
institution will not release a tissue block (4 slides for lung tissue or 12 slides for 
DLBCL tissue). A FFPE block is preferred. 
FFPE tissue collected for genomic analysis may not be submitted for the tissue 
requirements for pathology review. Separate tissue slides must be submitted to or 
prepared by the AMC Biorepository for pathology review. The AMC Biorepository 
will cut slides from the FFPE block and distribute all slides for pathology review 
according to HTMCP SOPs. The AMC Biorepository will return all tissue blocks 
to the site after cutting slides for pathology review. Frozen tumor tissue or FFPE 
tissue scrolls will be sent to GSC-BC for genomic analysis. 
5.1.2 Peripheral blood mononuclear cells (PBMC) sample for germline DNA 
All live participants in this study who are able and willing to provide a blood sample 
will have one 10 mL sample of peripheral blood drawn by venipuncture or 
cannulation of an indwelling venous access device. This sample will be used for 
germline DNA analysis. This blood draw will occur at the same time as a blood 
draw for routine medical care. Sites submitting tumor samples collected 
retrospectively may still collect a blood sample for PBMC even if the participant 
has already started treatment for the malignancy. 
Samples will be collected in a tube containing either EDTA or acid citrate dextrose 
(ACD) anticoagulant and transported to the local laboratory for processing PBMC 
within 2 hours of collection (according to HTMCP SOP#206, Processing Non-
Tumor Samples for the HIV+ Tumor Molecular Characterization Project, Blood 
Cells). PBMC samples should be prepared and frozen according to Appendix III to 
prevent hemolysis. After processing blood samples for PBMC, the site will ship 
frozen samples to the AMC Biorepository in accordance with Appendix IV. Please 
contact the AMC ODMC with questions about processing blood for PBMCs; 
alternate processes for PBMC isolation may be approved at the discretion of OCG. 
If the initial PBMC sample submitted is found to be insufficient for normal DNA 
analysis, OCG and/or the AMC ODMC will notify the site that an additional blood 
specimen may be collected from the participant. The additional blood specimen 
must be processed for PBMC in accordance with the requirements listed above. 
5.2 
Sample Storage 
5.2.1 Sample identification and assurance of anonymity 
Participant material will be obtained in the inpatient or outpatient setting. In either 
case, samples of tumor, blood, bone marrow, and/or skin will be initially identified 
with a 9-digit AMC participant ID number in the AdvantageEDC and GlobalTrace 
systems. All study specimens will be shipped to the AMC Biorepository. 
5.2.2 Deposition of samples in the laboratory 
The principal investigator or his/her designee will be responsible for shipping 
specimens to the AMC Biorepository in accordance with Appendix IV. Specimens 
shipped to the AMC Biorepository will be identified by participant ID and sample 

 
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number. The AMC Biorepository will transfer specimens to the ACSR for storage. 
Samples will be stored at the ACSR at -80oC or colder. The ACSR will be 
responsible for following the HTMCP SOPs as they relate to sample handling, 
labeling, and shipping. 
5.3 
Biopsies Negative for Malignancy 
If biopsy is performed for the purpose of diagnosing suspected malignancy, and the biopsy 
submitted for the purposes of this protocol is later found to be negative for malignancy, no 
additional tissue specimens will be collected for the purpose of this study and no health 
information will be recorded in the study database. Unless the participant provides consent 
for ACSR donation for the future use of his/her specimens, all study samples collected 
from participants who are found negative for malignancies will be destroyed. 
5.4 
Sample Analysis 
Frozen and FFPE samples will be stored at the ACSR until shipping is arranged to the 
GSC-BC. At the GSC-BC, samples will undergo genomic analysis using study-generated 
ID numbers. PHI will never be available to investigators involved with any stage of the 
genomic analysis. 
Samples will be analyzed at the GSC-BC by full genomic sequence analysis. For this 
purpose, DNA will be extracted, sheared, and Illumina sequencing performed in order to 
obtain 80x genome coverage. Comparisons will be made between tumor and normal DNA 
to identify the somatic changes associated with cancer. Frequency of mutations within a 
sample will be determined by deep sequence analysis. RNA will be sheared, reverse 
transcribed, and sequenced to assess transcribed sequences. 
Genomic analyses performed on these samples may include, but are not limited to, array-
based gene expression profiling, comparative genome hybridization, and single nucleotide 
polymorphism studies, as well as whole genome sequencing analysis using the most current 
genomic technology available. The goal of comprehensive genomic analysis is to 
document all the genetic abnormalities associated with malignancy and other virus 
malignancies. 
To facilitate discovery and collaboration, de-identified DNA sequences from consenting 
participants will be shared with other investigators performing similar research. De-
identified retrospective cases may be submitted with the available follow-up data relative 
to the diagnosis date.The way in which this genetic information is shared is described in 
Appendix II. As the AMC is a Federally-funded cooperative group, the AMC is obligated 
to disseminate research findings. This will be facilitated by sharing genetic testing results 
from all AMC specimens collected on this protocol using registries such as dbGaP, the 
Database of Genotypes and Phenotypes. Data submitted to dbGaP includes sensitive 
information; however, this information, such as de-identified phenotypes and genotypes 
for individual study participants, will only be available via a controlled-access database. 
All data entry in dbGaP for this study will be performed by GSC. 
Controlled-access data can only be obtained if a user has been authorized by the appropriate 
Data Access Committee. All AMC members have access to information obtained from 
AMC samples. 

 
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dbGaP also provides an open level of access, but this involves only the release of non-
sensitive data such as the study summary and/or protocol document, the contents of 
measured variables in aggregate, and genotype-phenotype analyses. Submitters to dbGaP 
must identify any limits on the use of data specifically set through the informed consent 
form (either as a whole or on a case-by-case basis) and their IRB must review and provide 
GWAS institutional certification for the submission of data (template Institutional 
Certification available at HTMCP SOP#105). 

 
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6.0 
CLINICAL INFORMATION AND MAINTENANCE OF AN HIV-MALIGNANCY 
DATABASE 
6.1 
Data Collection 
Details of clinical information are in the protocols for each malignancy type in the HTMCP 
SOP manual. 
For participants of interest (i.e., participants whose samples will be sequenced), complete 
clinical information will be obtained. Information will be obtained by the investigators 
through review of the participant’s inpatient and outpatient medical records and by 
discussing the case with the participant’s physicians. Information will include 
demographics (race, ethnicity), vital status of the participant, date of last contact with the 
participant, history of the presenting illness, history or prior malignancy, date of 
pathological diagnosis, method of initial pathologic diagnosis, neo-adjuvant therapy and 
other therapies prior to tissue procurement and response to each therapy, date of tissue 
collection and fixative buffer pH (if applicable), date or progressive disease if applicable, 
primary site of progressive disease if applicable, surgical resection date if applicable, 
tobacco use history, date of HIV diagnosis, prior AIDS defining co-morbidities, co-
infections, HAART treatment prior to and at time of malignancy diagnosis, HIV risk group, 
history of other malignancies, cause of death and duration from diagnosis to death if 
applicable, relevant past medical history, Karnofsky or ECOG performance score, 
information regarding the physical exam, results of initial laboratory tests (hemoglobin, 
LDH, uric acid including CD4 count at nadir and time of malignancy diagnosis, HIV RNA 
load at time of malignancy diagnosis) and imaging tests, results of the diagnostic tumor 
biopsy and bone marrow biopsy, and results of flow cytometry, cytogenetics, and 
molecular studies. 
6.2 
Duration of Follow-up Data Collection 
Participants will be followed prospectively to record the types of treatment given, and 
treatment outcome and toxicity. Follow-up information will include the results of 
subsequent laboratory and imaging tests, pathology, cytogenetic and molecular diagnostic 
reports, and records describing the participant’s course in the inpatient and outpatient 
setting. 
Participants will remain on study for data reporting purposes for up to 2 years after 
enrollment. Data abstraction for follow-up will occur at 12 and 24 months (± 4 weeks) after 
the date of initial diagnosis stated in the HTMCP enrollment form. Follow-up forms will 
be completed using the HTMCP’s paper forms and will be submitted via forms upload in 
AdvantageEDC. The Follow-up Form will be requested for the 1 and 2 year milestones for 
accepted cases. In the event the participant declines further participation, expires, is lost to 
follow-up, or is removed from study follow-up by the investigator, the Off Study Form 
must be submitted in AdvantageEDC. 

 
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6.3 
Recording Information in the Database 
Information will be entered into the HTMCP forms and reviewed by the principal 
investigator at each site or his/her designee. Only the PI and those who enter the data will 
have access to the database at the AMC sites. Data forms will be uploaded into 
AdvantageEDC. The AMC ODMC will enter all data from submitted forms in the 
HTMCP’s database. 

 
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7.0 
DISTRIBUTION OF SAMPLES TO RESEARCHERS 
All material(s) received by the AMC Biorepository at George Washington University 
(GWU) will be transferred to the AIDS and Cancer Specimen Resource (ACSR) within 24 
hours of receipt. 
The specimens collected under this protocol are primarily for the use of the Genome 
Science Center (GSC) in fulfillment of their role as characterization center for the HIV 
Tumor Molecular Characterization Project. All collected samples will be sent to GSC-BC 
for validation and characterization. Returned remnant specimens and associated clinical 
information can be requested by AMC investigators, the NCIs Genome Science Center and 
other investigators through a Letter of Intent (LOI) to the ACSR. Requests should include 
rationale for the study, proposed analysis, type and quantity of specimens, and clinical 
information required. Approval from the Human Research Protection Office of the 
requestor’s institution will be required for studies using samples from the tissue repository. 
The ACSR’s independent review panel will evaluate LOIs based on factors including, but 
not limited to, scientific merit, availability of samples, and scientific priorities. Once an 
LOI is approved, the ACSR will send the specimen to the approved party and will work 
with the AMC ODMC and GSC to obtain the requested clinical information in a coded and 
de-identified fashion. 
The ACSR will serve as the “honest broker” and will be responsible for linking the data 
and specimens by UPN prior to providing information to researchers who wish to obtain 
linked data and specimens to minimize the risk of breach of confidentiality. 
Individual results/data from any study using material from the tissue repository will not be 
disclosed to the participant or physician except in extraordinary circumstances when 
nondisclosure is deemed to be unethical and then only after consultation with the Human 
Research Protection Office of each university. 

 
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8.0 
POTENTIAL RISKS 
As a laboratory study involving only sample collection through routine clinical care and 
data abstraction, no adverse events will be collected for this study. 
8.1 
Risks of Tumor or Node Biopsy 
For some participants, the tumor specimen will be acquired via a lymph node biopsy or a 
biopsy of an extranodal site, including bone marrow. The risks of the biopsy vary with the 
site, but generally include local discomfort, bleeding, and infection. All participants on 
study will have the biopsy performed in the course of routine medical care. 
Participation in the study will entail no additional risks attributable to the procedure if the 
malignancy specimen is obtained via a surgical biopsy for routine medical care. 
8.2 
Risks of Blood Collection 
There is a very small risk of infection or bleeding associated with venipuncture. 
8.3 
Breach of Confidentiality 
Despite the extensive security measures employed to de-link the identities of participants 
and their donated tissue specimens, there is a possibility that the identities of participants 
enrolled in this study could be discovered or linked to genetic sequence data obtained from 
their tissue specimens. Consequently, it is possible to use this information to link them to 
the identities of their children, parents, siblings, and other relatives. It may be possible to 
identify participants as carriers of genetic mutations. It is also possible that there could be 
violations of the security used to store the codes linking participant’s genetic information. 

 
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9.0 
STATISTICAL CONSIDERATIONS 
This is a descriptive study of the mutational spectrum in each type of HIV-1 associated 
malignancy. No statistical analyses are planned for this protocol. 

 
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10.0 
ROLE OF DATA MANAGEMENT 
10.1 
CRF Instructions 
Instructions concerning the recording of study data on the HTMCP’s paper CRFs will be 
provided by the NCH and made available to participating sites by the AMC ODMC at 
www.AIDSCancer.org. Fillable PDF forms will be used for all clinical data collection for 
the HTMCP. All forms will be uploaded in AdvantageEDC for tracking purposes. The 
AMC ODMC will manage all data entry in the HTMCP project database (managed by the 
NCH) on behalf of sites. 
10.2 
Data Quality 
It is the responsibility of the AMC ODMC to assure the quality of data for the study (See 
Appendix I, AMC Data and Safety Monitoring Plan). This role extends from protocol 
development to generation of the final study database. 
10.3 
Data Monitoring 
This study will be monitored by the Clinical Data Update System (CDUS). Cumulative 
CDUS data will be submitted quarterly to CTEP by electronic means. Reports are due 
January 31, April 30, July 31, and October 31. 

 
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11.0 
ETHICAL CONSIDERATIONS 
11.1 
Informed Consent 
The principles of informed consent described in Food and Drug Administration (FDA) 
regulations (45 CFR Part 46) must be followed. The AMC ODMC must receive a copy of 
the letter of approval from the IRB, which specifically approves the protocol and informed 
consent, before participant enrollment. The IRB must also approve any significant changes 
to the protocol and documentation of this approval must be submitted to the AMC ODMC. 
Records of all study review and approval documents must be kept on file by the 
Investigator and are subject to inspection during or after completion of the study. Any AEs 
related to the study procedures must be reported to the IRB in compliance with local 
requirements. The IRB should receive notification of completion of the study and final 
report within 3 months of study completion and termination. The Investigator will maintain 
an accurate and complete record of all submissions made to the IRB, including a list of all 
reports and documents submitted. 
All living participants who are reachable to approach for participation will be required to 
provide written informed consent prior to inclusion of their samples in the tumor bank. 
Unless a waiver is granted for the requirement for the informed consent process for 
participants who cannot be contacted, the consent must be freely given, with the 
understanding that it may be withdrawn at any time, and the informed consent form must 
be given in writing.  
If for any reason a participant in the study withdraws consent for the continued research 
use of the tissue samples, the samples will be disposed according to Institutional or ACSR 
guidelines on the handling of medical waste, depending on the party that has possession of 
the samples at the time of withdrawal. 
11.1.1 Request for a waiver of the requirement for informed consent 
A request to waive the requirement to obtain informed consent is being requested 
with protocol version 7.0 for archival sample and data collection and analysis for 
participants who cannot be reached for a consent discussion.. A model informed 
consent document is available if the IRB at a participating site denies a waiver of 
consent. Deceased participants may be included provided that the data are recorded 
as described below; research involving deceased persons is not considered human 
subjects research. 
The investigator believes this study meets the following requirements for this 
request per 46 CFR 46.116(d). The pre-2018 Human Subjects Protections 
regulations are cited as follows, as the trial ws initiated at participating centers 
under these regulatory requirements: 
• The research involves no more than minimal risk to the participants. The only 
risk is the loss of patient confidentiality, which will be minimized as described 
in the confidentiality section (Section 8.3). 
• The waiver or alteration will not adversely affect the rights and welfare of the 
participants. There will be no contact with the participants or their next of kin 

 
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and no documentation of this study in their medical records. 
• The research could not practicably be carried out without the waiver or 
alteration. As described above, these diseases are very rare, and consent of live 
participants for archival cases is not feasible for all available cases. Consent of 
deceased participants is not feasible. Enrollment of the trial in a reasonable time 
frame has not proven feasible without access to archival specimens . 
• The project could not practicably be conducted without the use of PHI. PHI 
collected will be limited to dates, such as the year of diagnosis, treatment, 
response, and diagnosis. Collection of select dates is necessary to obtain data 
elements that are required to determine participant eligibility and are important 
to the question being studied. The AMC also requires collection of demographic 
data (participant initials, birth date, and zip code) in standard forms for audit 
verification, assurance that each participant enrolled is unique, and required 
demographic reporting to the NCI. These details will be removed from the 
dataset before transfer to OCG, with birthdate converted to age. 
• An adequate plan to protect identifiers from improper use and disclosure is 
included in the research proposal. Only authorized study personnel have access 
to this information in AdvantageEDC, which is secured from unauthorized 
access with login/password controls. Participant initials are encrypted in the 
AdvantageEDC data entry system and in the study database, and can only be 
viewed in AdvantageEDC by the clinical site staff. Access of de-identified 
records through the HTMCP and dBGaP is described in Section 6.1 and Section 
7.0. 
• An adequate plan to destroy the identifiers at the earliest opportunity, or 
justification for retaining identifiers, is included in the research proposal. The 
PHI collected is a component of standard AMC data entry forms for compliance 
with NCI demographic reporting requirements, and is also required for data 
analysis. Protections for this information will be applied as stated above. 
• The project plan includes written assurances that PHI will not be reused or 
disclosed for other purposes. Data access will be restricted to the parties listed 
in Section 7.0 and will not be reused or disclosed for any other purpose. No 
PHI, including dates, will be included in any study publications. 
• The AMC routinely provides study summaries for participants on its website. 
A waiver of HIPAA Authorization is being requested for this study. As described 
above, the use or disclosure of PHI involves no more than minimal risk; granting 
of the waiver will not adversely affect privacy rights or the welfare of the 
individuals whose records will be used; the project could not practicably be 
conducted without a waiver; and the project could not practicably be conducted 
without use of PHI. Further, the privacy risks are reasonable relative to the 
anticipated benefits of research, as the importance of the knowledge that may 
reasonably be expected to result outweighs the minimal risk posed to participants. 
PHI will not be re-used or disclosed for other purposes and, whenever appropriate, 

 
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the participants will be provided with additional pertinent information after 
participation. In accordance with Good Clinical Practice and the retention of 
records under 45 CFR 46.115, study records will not be destroyed until at least three 
years after the completion of the research. Only de-identified data will be retained. 
In addition, any institution(s) conducting research according to the guidelines of 
this protocol is required to adhere to local and state laws and regulations governing 
the confidentiality and disclosure of health information. 
11.2 
Changes to the Protocol 
Any change or addition to this protocol requires a written protocol amendment that must 
be approved by the Investigator and the IRB/IEC before implementation. 
11.3 
Women and Minorities 
This study is being conducted by the NCI-sponsored AIDS Malignancy Consortium 
(AMC). As part of their contractual obligations, each participating site within the AMC 
and the AMC as a whole is required to assure that the participation of women and minority 
participants reflects the percentage representation of these populations in their geographic 
region and, for the AMC, the United States as a whole. As such, it is expected that the 
representation of participants on this trial will reflect the constitution of the respective 
populations. 
Accrual Targets 
Ethnic Category 
Sex/Gender 
Females 
 
Males 
 
Total 
Hispanic or Latino 
24 
+ 
47 
= 
71 
Not Hispanic or Latino 
43 
+ 
86 
= 
129 
Ethnic Category: Total of all subjects 
67 (A1) 
+ 
133 (B1) 
= 
200 (C1) 
Racial Category 
 
American Indian or Alaskan Native 
1 
+ 
3 
= 
4 
Asian 
1 
+ 
3 
= 
4 
Black or African American 
24 
+ 
46 
= 
70 
Native Hawaiian or other Pacific Islander 
1 
+ 
1 
= 
2 
White 
40 
+ 
80 
= 
120 
Racial Category: Total of all subjects 
67 (A2) 
+ 
133 (B2) 
= 
200 (C2) 
 
(A1 = A2) 
 
(B1 = B2) 
 
(C1 = C2) 
11.4 
Confidentiality 
Breach of confidentiality is likely the greatest risk of participating in this study. Every 
effort will be exerted to minimize this risk. Maintaining confidentiality of both specimens 
and clinical data will be the responsibility of the principal investigator and staff (which 
includes but is not limited to the staff of the laboratory and the study coordinator). 
It may be desirable to contact participants at a later time to request additional information 
or to solicit participation in therapeutic trials. If the participant agrees to future contact as 

 
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discussed in their consent, the participant will first be contacted by one of the investigators 
of this study. If the participant agrees, then contact information will be provided to the 
Principal Investigator of the other trial. Whether a participant consents to future contact 
will be tracked in the study database. 

 
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12.0 
REFERENCES 
1. Boshoff C, Weiss R: AIDS-related malignancies. Nature Reviews in Cancer 2002, 2:373-382. 
2. Moore PS, Chang Y: Timeline: Why do viruses cause cancer? Highlights of the first century 
of human tumour virology. Nature Reviews in Cancer 2010, 10:878-888. 
3. zurHausen H: Papillomaviruses in the causation of human cancers - a brief historical account. 
Virology 2009, 384:260-265. 
4. Marur S, D'Souza G, Westra WH, Forastiere AA: HPV-associated head and neck cancer: a 
virus-related cancer epidemic. Lancet Oncology 2010, 11:781-789. 
5. Pattle SB, Farrell PJ: The role of Epstein-Barr virus in cancer. Expert Opinions in Biological 
Therapy 2006, 6:1193-1205. 
6. Wong EL, Damania B: Linking KSHV to human cancer. Current Oncology Reports 2005, 
7:349-356. 
7. Barmak K, Harhaj E, Grant C, Alefantis T, Wigdahl B: Human T cell leukemia virus type I-
induced disease: pathways to cancer and neurodegeneration. Virology 2003, 308:1-12. 
8. Silverman RH, Nguyen C, Weight CJ, Klein EA: The human retrovirus XMRV in prostate 
cancer and chronic fatigue syndrome. Nature Review in Urology 2010, 7:392-402. 
9. Mason AL, Zhang G: Linking human beta retrovirus infection with primary biliary cirrhosis. 
Gastroenterology Clinical Biology 2010, 34:359-366. 
10. Perl A, Fernandez D, Telarico T, Phillips PE: Endogenous retroviral pathogenesis in lupus. 
Current Opinion in Rheumatology 2010, 22:483-492. 
11. Boschoff C, Weiss R: AIDS-related malignancies. Nature Reviews in Cancer 2002, 2:373-382. 
12. Silverberg MJ, Abrams DI: AIDS-defining and non-AIDS defining malignancies: cancer 
occurrence in the antiretroviral therapy era. Current Opinion in Oncology 2007, 19:446-
451. 
13. Patel P, Hanson DL, Sullivan PS, et al. Incidence of types of cancer among HIV-infected 
persons compared with the general population in the United States, 1992-2003. Ann Intern 
Med. 2008;148:728-736. 
14. Chirenje ZM. HIV and cancer of the cervix. Best Pract Res Clin Obstet Gynaecol. 
2005;19:269-276. 
15. Lee W, Jiang Z, Liu J, et al. The mutation spectrum revealed by paired genome sequences from 
a lung cancer participant. Nature 2010; 465:473–477. 
16. Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A, Wells VA, Grunn A, 
Messina M, Elliot O, Chan J, Bhagat G, Chadburn A, Gaidano G, Mullighan CG, Rabadan 
R, Dalla-Favera R. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat 
Genet. 2011 Jul 31;43(9):830-7. 
17. Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011 
Feb;12(2):175-80. 

 
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APPENDIX I: AMC DATA AND SAFETY MONITORING PLAN 
Version 9.0  October 6, 2020 
 
Introduction 
The AIDS Malignancy Consortium (AMC) Data and Safety Monitoring Plan (DSMP) outlines the 
measures employed by the group to monitor the safety of participants and ensure the data validity 
and integrity for all clinical trials it conducts. This includes methods to: 1) monitor the progress of 
trials and the safety of participants; 2) comply with regulatory requirements for adverse event (AE) 
reporting; 3) processes for trial termination or temporary suspension and major modifications; and 
4) plans for ensuring data accuracy and protocol compliance. As the AMC conducts protocols of 
varying research phase, region of conduct (which may include trials conducted in the U.S., 
international sites, or both), IND sponsor (AMC investigator, CTEP, or industry-sponsored) and 
clinical data entry system use, this plan addresses broad processes applying to the range of trial 
designs and requirements. Refer to the individual AMC protocol to identify the applicable study 
characteristics for the relevant requirements described in this plan. 
Monitoring the Progress of Trials and the Safety of Participants 
Routine and expedited AE reporting 
All AMC protocols that collect safety data adhere to the National Cancer Institute (NCI), Cancer 
Therapy Evaluation Program (CTEP) Guidelines: Adverse Event Reporting Requirements 
(https://ctep.cancer.gov/protocolDevelopment/adverse_effects.htm), as applicable to the clinical 
protocol. AEs are to be recorded in the source documents, assessed by a clinical investigator for 
the AE reporting criteria, and promptly reported in the clinical data entry system as required by 
each protocol. For AMC trials conducted under a CTEP IND and AMC trials conducted within the 
U.S., all AEs that meet the NCI’s expedited reporting requirements are reported to the NCI via the 
CTEP Adverse Event Reporting System (CTEP-AERS) web application, either directly or through 
integration with Medidata Rave where this system is employed for AMC protocols. Use of this 
system ensures notification to the protocol chair and Investigational Drug Branch (IDB) at CTEP, 
as required for trials conducted under a CTEP IND, and a uniform expedited reporting and safety 
review process for AMC domestic trials. The system may also be programmed to include sponsor 
notification as required for trials with industry support. Alternate process for expedited AE 
reporting to the AMC protocol chairs and AMC Operations and Data Management Center 
(ODMC) within the clinical data entry system (AdvantageEDC or Advantage eClinical only) may 
be defined in the protocol for select trials (international studies and The ANCHOR Study). 
All serious adverse events (SAEs) received by the AMC ODMC will be reviewed by the AMC 
medical monitor at the AMC ODMC for consideration of individual participant safety, safe trial 
conduct, data reporting quality for AE term selection, and appropriate application of the regulatory 
criteria for seriousness, expectedness, and relatedness to the investigational therapy. If alternate 
procedures are followed for SAE review, the process for adequate medical monitoring will be 
defined in the AMC protocol and the Transfer of Regulatory Obligations (TORO) with the sponsor. 
AMC medical monitor review includes review of the CTEP-AERS report before CTEP submission 
for IDB review (if applicable), or review of the SAE report in the data entry system for trials not 
using CTEP-AERS for expedited reporting. The IND sponsor or its designee will issue the 

 
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determination as to whether the AE requires IND safety reporting to FDA as a serious and 
unexpected suspected adverse drug reaction (SUSAR). For protocols not conducted under an IND, 
in the event of disagreement between the reporting physician and the AMC medical monitor 
regarding the relationship of the AE to the investigational agent(s) (i.e., determination of whether 
the attribution is unrelated or unlikely, or possible, probable, or definite), the AMC medical 
monitor will provide the final determination of the relationship. IND safety reporting to FDA is 
performed by CTEP for trials conducted under a CTEP IND; IND safety reporting is performed 
by the sponsor or sponsor’s designee (AMC ODMC or other party defined in the study agreement 
or TORO) for IND studies sponsored by AMC investigators or industry sponsors. 
Expedited reporting to the Institutional Review Board (IRB) 
The requirements for IRB review will be identified in the protocol section on ethical and regulatory 
obligations. All AMC trials initiated before September 1, 2020 and all international sites for all 
AMC studies are subject to local IRB review; only U.S. sites are subject to the NCI requirement 
to use a single IRB for protocols initiated on or after September 1, 2020. For trials subject to local 
IRB review, the site principal investigator is responsible for ensuring that expedited AE reports 
for its trial participants and any unanticipated problems that affect the local institution only are 
submitted to the local IRB of the reporting institution, per the local IRB’s requirements for such 
reporting. For studies reviewed by the single IRB, the protocol chair will render a determination 
as to whether a SAE or other problem constitutes a trial-wide unanticipated problem that requires 
reporting to that IRB, in accordance with its standards of procedure.  
To comply with investigator notification requirements for IND studies under 21 CFR 312.32 and 
312.55, IND safety reports from all trials the AMC conducts and reports from external sponsors 
investigating the same agents are made available to all investigators upon receipt from the sponsor 
or its designee, either via the password-protected section of the AMC Operations web site (AMC 
trials subject to local IRB review only) or the CTSU website (U.S. trials subject to single IRB 
review/CTEP IND agents). The site clinical investigator responsible for the applicable AMC 
protocol(s) is responsible for reviewing any IND safety reports received and documenting 
submission to the IRB of record (if required by local policy) within the timeline defined by the 
Clinical Trials Monitoring Branch (CTMB) audit guidelines. 
Procedures for monitoring trial progress and pharmacovigilance 
For trials using AdvantageEDC or Advantage eClinical for clinical data entry, the AMC ODMC 
provides on demand tabular listings of all reported AEs and SAEs on a participant level to the 
protocol chair and co-chair(s) for review via the password-protected section of the AMC 
Operations web site, www.AIDScancer.org. For trials using OPEN and Medidata Rave for clinical 
data collection, data listing will be made available using that system. Summary reports of AEs by 
frequency and relationship to the investigational agent(s) are provided to all AMC investigators 
and their staff It is the responsibility of each site to provide trial-specific AE listings to their 
respective IRB, if required by its policies. For blinded studies, the AE and SAE listings are 
reviewed and tabulated without treatment assignment. 
Accrual summaries for each AMC trial are updated nightly on the password-protected section of 
the AMC web site. The progress of each AMC trial is reviewed regularly by the protocol chair and 
also by the appropriate Scientific Working Group (SWG) during scheduled conference calls 
(monthly SWG calls and as required, protocol-specific monitoring conference calls). Summary 

 
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accrual, summary AE, and individual SAE reports are provided to SWG leadership and protocol 
chairs to monitor participant safety during these monthly calls. 
The AMC medical monitor reviews listings of all reported AEs on a quarterly basis for assuring 
compliance with the protocol requirements for AE reporting and the identification of any safety 
concerns (individual AE or increased frequency/severity of expected AEs) for the agents under 
investigation. Findings from these reviews are communicated to the protocol chairs and all AMC 
investigators, and posted to the AMC Operations web site. 
Data and Safety Monitoring Board Review (DSMB) review 
The AMC has formed an independent Data and Safety Monitoring Board (DSMB) for AMC trials 
and for the ANCHOR Study. As required by NCI policy, the AMC requires DSMB review for all 
phase III randomized trials. All other clinical trials that the AMC initiates will be reviewed by the 
AMC ODMC and AMC Statistical Center during protocol development to issue a recommendation 
as to whether the study requires DSMB oversight, which will require the approval of the AMC 
Executive Committee. This determination will be based on the phase of the study, experimental 
design, risk posed by the investigational approach, extent of data available on the safety of an 
investigational agent, risk posed by the natural course of the health condition under research, and 
the categories of vulnerable populations involved. The involvement of a DSMB in reviewing an 
AMC protocol will be identified in each clinical protocol as approved by CTEP and, as applicable, 
required by the IRB of record. 
Regarding the composition of the AMC DSMB, voting members usually include physicians, 
statisticians, an ethicist, and a patient advocate. All voting members have no other affiliation to 
the AMC and are appointed by the AMC Executive Committee with the approval of the OHAM 
Director. Nonvoting members are the AMC group statistician, the protocol statistician, an AMC 
ODMC staff member, two representatives (normally a clinician or statistician) from CTEP, and 
the grant program directors from the NCI Office of HIV and AIDS Malignancy (OHAM). 
The DSMB reviews all applicable AMC studies in accordance with the National Cancer Institute’s 
Policy for Data and Safety Monitoring. Confidential reports of all trials under review are prepared 
by the AMC group statistician with support from the AMC ODMC. A written report containing 
the current status of each trial monitored, and when appropriate, any toxicity and outcome data, 
are sent to DSMB members by the AMC ODMC within the timelines specified by the DSMB 
charter. This report addresses specific toxicity issues and any other concerns about the conduct of 
the trial, as defined by the protocol plan for DSMB review. The report may contain information 
for the DSMB to render determinations for participant safety, early trial termination, results 
reporting, or continuing accrual or follow-up. 
The results of each DSMB meeting are summarized in a formal report sent by the DSMB chair to 
the AMC group chair and AMC ODMC. The DSMB report contains recommendations on whether 
to close each study reviewed, whether to report the results, and whether to continue accrual or 
follow-up. A primary recommendation (e.g., continue with no change; recommended or required 
modification; stop) must be included in the document. The group chair or designee is then 
responsible for notifying the protocol chair and relevant SWG chair before the recommendations 
of the DSMB are carried out. In the unlikely event that the protocol chair does not concur with the 
DSMB, then the OHAM program directors and the NCI division director or designee must be 
informed of the reason for the disagreement. The protocol chair, relevant SWG chair, group chair, 

 
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DSMB chair, and NCI division director or designee will be responsible for reaching a mutually 
acceptable decision about the study. CTEP approval of a protocol amendment will be required 
prior to any implementation of a change to the study. 
Following a DSMB meeting, the DSMB’s recommendations are provided to all AMC investigators 
and staff. It is each site principal investigator’s responsibility for conveying this information to its 
local IRB as relevant for its protocol participation. For trials reviewed by a single IRB, the AMC 
ODMC will support notification to the IRB as required per its procedures. 
Cohort trial reviews not subject to DSMB review 
For phase I dose escalation trials, dose escalation (or dose de-escalation) is based on the rules in 
the protocol and the protocol chair, AMC medical monitor, and protocol statistician determine 
whether these criteria have been met based on a review of all safety data for the protocol-defined 
evaluation period. If applicable for phase II trials, stopping the trial for toxicity or efficacy, or 
suspending enrollment pending observation of responses in a multi-stage phase II trial, is based on 
meeting criteria stated in the protocol, and the protocol chair, AMC medical monitor, and protocol 
statistician determine whether these criteria have been met. 
Plans for Assuring Compliance with Requirements Regarding AE Reporting 
The protocol chair, AMC group chair, and the AMC ODMC share responsibility in assuring that 
participating investigators comply with applicable regulatory and protocol requirements for AE 
reporting. The AMC site principal investigator certifies compliance with NCI and FDA 
requirements for trial conduct by signing the site subaward agreement for the grant and the AMC 
Adherence Statement for site membership; clinical investigators also certify compliance in 
completing the protocol signature page for each protocol active at the site, and Form FDA-1572 
for CTEP investigator registration, and also for AMC IND studies sponsored by AMC 
investigators or industry sponsors. Protocol compliance with AE identification, assessment and 
reporting requirements is assessed by the AMC ODMC using several methods: 1) programmed 
system checks and messages to instruct the site to complete routine and/or expedited reporting 
when certain criteria are reported in the clinical data entry system; 2) programmed data reports 
provided to the protocol chairs that identify reports requiring expedited AE reporting; 3) remote 
review of data entry or data reports to ensure compliance with protocol and NCI AE reporting 
requirements; 4) AMC medical monitor review described in the section above; and, 5) routine site 
audits by reviewing the site’s source documentation. 
The clinical data entry systems used for AMC studies include the Oncology Patient Enrollment 
Network, OPEN for enrollment, and Medidata Rave for clinical data entry for enrolled 
participants; trials activated before September 1, 2020 or that involve only AMC international sites 
may be reported in AdvantageEDC/Advantage eClinical, a web-based data entry and enrollment 
system. These data entry systems are programmed to notify the site investigator, protocol chair, 
AMC medical monitor, and AMC ODMC via email in the event that a site reports an AE that 
meets expedited reporting criteria to NCI and/or FDA. Additional reporting conditions may be 
programmed depending on the sponsor reporting requirements of a given protocol (e.g., adverse 
events of special interest [AESI]). If the site does not follow with an expedited report, the AMC 
ODMC contacts sites to request compliance with reporting requirements. Additionally, the 
protocol chair, AMC ODMC, and the AMC medical monitor review reported AEs on a routine 
basis to identify AEs reported by sites that require expedited reporting. The protocol chair, AMC 

 
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SWG chairs, AMC group chair, and IND sponsors have general oversight for assuring that routine 
and expedited adverse reporting requirements are met by the responsible parties. 
For studies monitored by CTEP using the Data Mapping Utility (DMU), cumulative protocol- and 
patient-specific data will be submitted weekly to CTEP electronically via the DMU. For trials 
monitored by the NCI’s Clinical Data Update System (CDUS), AE information is transmitted 
electronically to NCI on a quarterly basis. For trials monitored by NCI’s Clinical Trials Monitoring 
Service (CTMS), AE information is transmitted electronically to NCI every two weeks. 
Plans for Assuring that any Action Resulting in a Temporary or Permanent Suspension of 
an NCI-Funded Clinical Trial is Reported to the NCI Grant Program Director Responsible 
for the Grant 
In the event that temporary or permanent suspension of a trial, or major modification to the 
protocol is under consideration, the protocol chair will convene the AMC ODMC, AMC Statistical 
Center, and SWG chair by conference call to discuss the options. Suspension actions will also be 
reviewed by the AMC Executive Committee for program oversight and direct communication of 
the action with the OHAM program directors. For phase III trials, closure decisions are typically 
rendered by the AMC DSMB; if the trial in question is under AMC DSMB oversight but rendered 
by the AMC investigators, the AMC DSMB will be notified of the suspension and the reason. For 
phase I and II trials, the protocol chair also has the option of asking the DSMB to review the study. 
The AMC ODMC will inform the CTEP Protocol Information Office (PIO), with copy to OHAM 
Directors, when studies are temporarily or permanently closed. In the event of major trial 
modification, CTEP must approve all protocol amendments prior to distributing to the AMC sites. 
Plans for Assuring Data Accuracy and Protocol Compliance 
All study data for AMC clinical trials are entered directly by AMC clinical site staff into the 
applicable clinical data entry system for the trial. During data entry, the system performs validation 
checks on many fields and performs consistency checks between select fields. Range checks are 
placed on each field to eliminate entry of out-of-range values. Edit check programs are run on the 
database on a set schedule to identify and resolve inconsistencies between forms or data collected 
at different points in time. Submitted data entry forms are reviewed for compliance with the 
protocol and data entry instructions according to the AMC ODMC’s standards for data quality 
processes. AMC ODMC staff routinely interacts with site staff to resolve any data submission 
problems. 
In accordance with NCI guidelines, the AMC ODMC conducts audits at the AMC sites to evaluate 
compliance with regulatory issues, and to review data for specific cases by checking source 
documents. These reports are sent to the site principal investigator and to the NCI. In the event 
that major violations are identified, sites are asked to provide a written corrective and preventative 
action plan to correct deficiencies. If needed, a repeat site audit is conducted. In the event that a 
site does not correct deficiencies in a pre-determined time frame, the AMC Executive Committee 
has the option to implement remedial action(s) for the site. Possible actions include, but are not 
limited to, suspending enrollment of new patients to AMC trials until deficiencies are corrected; 
recommending a decrease in funding to the site; and requiring specific training for site 
investigators or staff members. 
 

 
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APPENDIX II: HTMCP DATA USE AND ACCESS POLICY 
Research Plan 
Samples will be processed and analyzed at the GSC by high-coverage genomic and transcriptomic 
sequencing. The results will be analyzed will be made between tumor and normal DNA to identify 
the somatic changes present in the cancer tissues. These alterations include detection of 
chromosomal changes, such as, but not limited to, amplification (and levels), deletions, loss of 
heterozygosity, translocations, etc., expression profiling as well as detection of transcripts resulting 
from translocations and mutations, including single nucleotide variants, insertions, deletions, etc. 
The results from the tumors of one type will be examined for patterns of common changes, 
including mutations as a first step to identify the molecular changes that drive the cancer etiology. 
The alterations will also be analyzed within the context of biological pathways and systems 
biology. 
Coding of Samples 
All biological materials and medical information will be coded in HTMCP. Only the designated 
gatekeeper at each Institution will keep the code key that matches the project identifying number 
to 
the 
personally 
identifiable 
information 
(http://datacenter.cit.nih.gov/interface/interface241/PIIguide.html; Note: this is applicable in the 
US, other countries may have different regulatory frames that must be complied with) using 
procedures in place and approved by the local institution. Researchers, including those who will 
be working with the participant samples and medical information, will not have access to any of 
the traditionally used identifying information about the participant. All materials submitted to the 
HTMCP will be labeled with a project-assigned ID. 
Storage and Release of Samples and Medical Information 
The coded tissue samples will be sent to the Genome Science Center of the British Columbia 
Cancer Agency (BC-GSC), which is the characterization center for the HTMCP. The samples will 
be processed there and the molecular analytes extracted from samples will be used for sequencing. 
Any remaining samples will be stored at the BC-GSC until the end of the project. At the end of 
the project, any remaining samples will be handled in accordance with the protocol of contributing 
institution as designated in the disposition form. 
Data stripped of identifiers, in compliance with the definition specified in the HIPAA Limited Data 
Set definition (http://hipaa.wisc.edu/ResearchGuide/limiteddatasets.html), will be submitted by 
the contributing institution to the Data Coordinating Center (DCC). The DCC serves as a central 
HTMCP project database. The DCC also stores the molecular profiling data generated with the 
DNA and RNA. 
Data Access 
• Information (data) from analyses of the coded samples and the coded medical information will 
be deposited into publicly available databases. These databases will be accessible by the 
Internet. Medical information and molecular characterization results on the coded samples will 
be stored in a controlled-access database. The information in this database will be available 
only to researchers have received approval from the NCI Data Access Committee after their 
institutions have certified their adherence to participant data protection policies for the project 

 
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(http://epi.grants.cancer.gov/dac/charter.html). 
• To ensure protection of genetic privacy for sample donors, data users will have to agree to 
certain conditions described in the HTMCP Patient Protection Policy and Controlled Access 
Policy as to how the data will be used. For example, users will have to agree that they will 
share these data only with others who have also completed a data access agreement and that 
they will not patent discoveries in a way that prevents others from using the data. This means 
that reviewers of a manuscript who need to see any controlled-access HTMCP data underlying 
a result must also agree to these user access conditions before they can see these data. 
• Anonymous information from the analyses will be put in a public database, available to anyone 
on the Internet. 

 
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APPENDIX III: PROCESSING BLOOD SAMPLES FOR THE HIV+ TUMOR 
MOLECULAR CHARACTERIZATION PROJECT 
(HTMCP SOP#206, Version 4.0) 
I. INTRODUCTION 
A. Scope and Purpose 
1. To establish a common procedure for blood processing prior to shipment to the AMC 
Biorepository. 
2. This protocol applies to all AMC sites providing tissues prospectively. AMC sites are 
also permitted to prepare PBMC aliquots according to the ACSR’s SOP, Separation of 
Plasma and Mononuclear Cells, available on the AMC Operations web site 
(www.AIDSCancer.org). 
3. Any deviation from this SOP should be noted in the lab notebook, indicating nature of 
deviation, times and which samples were affected. This information should be given 
within 48 hours of the occurrence to the Project Team (PT) representative by sending 
an email to ocg@nih.nci.gov with the details. 
B. Safety Precautions 
1. Wear personal protective equipment (PPE) such as lab coats and gloves. 
2. Liquid nitrogen is extremely cold and can cause ‘burns.’ Wear gloves that are specially 
made to withstand liquid nitrogen, eye protection (preferably Face Shield), and a lab 
coat to protect skin from splashes and spills. Liquid nitrogen is an asphyxiant; be sure 
to use in a well-ventilated area. 
C. Equipment and Materials 
1. Personal protective equipment (PPE) to include latex or nitrile gloves, heavy duty 
gloves, eye protection (preferably Face Shield), lab coat and closed-toe shoes 
2. Clinical Centrifuge with swinging bucket rotor 
3. 250 mL flask containing 50 mL bleach for waste disposal 
4. Cryovials (e.g., 2mL screw cap vials from ChartBiomed, Part Number 10778828) 
5. GlobalTrace labels 
6. Dewar thermo-flask 1L 
7. Liquid nitrogen 
8. Isopentane (2 methyl butane, certified grade) 
9. Three-prong beaker tongs 
10. PBMC separation tube 
11. Disposable transfer pipette 
12. 100 mL metal beaker 

 
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13. Long forceps, 8-12” 
14. Timer 
15. Fine point Cryomarker 
16. Disposable, sterile plastic transfer pipettes or sterilized glass Pasteur pipettes 
17. Ice bucket 
18. Dry ice 
II. PROCEDURE 
A. Collection 
1. Collect 10 mL of blood in a tube containing either EDTA or acid citrate dextrose (ACD) 
anticoagulant. 
2. Prepare an ice bucket with dry ice. Chill one 2mL cryovial to collect the white blood 
cells isolated in the procedure. The vial must be identified with a GlobalTrace label. 
B. Blood Separation 
1. Fractionate the whole blood by centrifuging at 1500-2000 X g for 10-15 min at room 
temperature. This will separate the blood into an upper plasma layer, a lower red blood 
cell (RBC) layer, and a thin interface containing the white blood cells (WBCs) / buffy 
coat (see Figure 1). Fractionate the blood as soon as possible after collection. 
NOTE: In a typical clinical centrifuge 1500-2000 X g is 
~3000-3400 rpm. Check the appropriate settings for your 
centrifuge using the nomogram in your user’s manual. 
2. Use a disposable plastic transfer pipet or Pasteur pipet to 
slowly and carefully aspirate the plasma (upper layer) down 
to about 1 mm above the buffy coat. Do not disturb the buffy 
coat. Discard the plasma into a 250 mL flask containing 
bleach. 
3.  Gently recover the buffy coat (WBCs) with a fresh 
disposable pipet, Pasteur pipet, or 1000 μl micropipettor 
with a sterile tip. Try not to uptake the RBC layer below the 
buffy coat. 
4. Place the recovered buffy coat into the WBC labeled 
cryovial cooled on ice from step 2. 
5. Screw on the cryovial cap tightly to prevent isopentane from 
seeping into the vial. 
6. Visually estimate the volume of WBCs recovered using the 
volume lines on the cryovial and write the information into the datasheet. Buffy coat 
volume is greater in samples with high WBC counts. Usually you can expect ≤ 0.5 mL 
total. 
7. Proceed to section C, “Freezing Collected Cells.” 

 
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C. Freezing Collected Cells 
1. Set Up Freezing Station 
• Do not perform snap freezing with bare hands. Wear gloves at all times and heavy 
duty gloves when working with liquid nitrogen or cooled isopentane. 
• Use extreme caution when dispensing liquid nitrogen. 
o Fill a small 100 mL metal beaker about 1/4 full with isopentane. 
o Fill the Dewar thermo-flask about 1/3 full with liquid nitrogen. 
2. Freezing Cells in Cryovials 
• Using beaker tongs lower the 100 mL metal beaker containing isopentane half-way 
into the liquid nitrogen for cooling. The liquid nitrogen will boil as the beaker is 
lowered. When the isopentane is reaching its freezing point the tone of the boiling 
will increase for 2-3 seconds. 
• Using beaker tongs, lift the beaker out of the liquid nitrogen once you see beads of 
solid isopentane at the bottom of the beaker (about 2 minutes). Place the beaker on 
the workbench. 
• Use long forceps to hold one to three cryovial(s) down into the cooled isopentane. 
Submerge cryovial(s) for at least 1 minute. 
• Take out the cryovial(s) containing frozen tissue. 
• Store frozen cryovial(s) in liquid nitrogen storage tanks or -80°C freezers. 
THE FROZEN SPECIMENS SHOULD BE KEPT FROZEN ON DRY ICE AT ALL 
TIMES DURING TRANSPORT TO AND FROM STORAGE TANKS. 

 
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APPENDIX IV: SHIPPING INSTRUCTIONS FOR SUBMITTING PBMC, SNAP 
FROZEN BIOPSY TISSUE, AND FORMALIN-FIXED TISSUE TO THE AMC 
BIOREPOSITORY 
A. GENERAL 
• It is the responsibility of the Primary Investigator to ensure that all staff personnel who will 
be handling, packaging, and/or shipping clinical specimens act in conformance with 
International Air Transport Association (IATA) regulations (IATA Packing Instruction 
650) relating to the handling and shipping of hazardous goods. (IATA Packing Instruction 
650 is located on the AMC website.) 
• Use a federally approved shipper for biological substance shipment (Category B). Label 
the shipper with the "Infectious substance" diamond-shaped label. On one side, in black 
marker write “Biological Substance, Category B, 
 your name or name of 
responsible person, date of collection, and phone number of the person responsible for the 
package. Package and label the shipment in accordance with the instructions provided for 
that specific shipper. 
• A Shipper’s Declaration for Dangerous Goods is not required. However, for all dry ice 
shipments, the following information must be shown in sequence on the airway bill in the 
“Nature and Quality of Goods” box: Dry Ice, Class 9, 
number of boxes being 
shipped, net weight of dry ice per box. 
 
NOTE: Specimens MUST BE SHIPPED Monday through Thursday as a PRIORITY 
OVERNIGHT shipment. Specimens are NOT ACCEPTED ON SATURDAYS OR 
SUNDAYS in the AMC Biorepository.  
B. SPECIMEN PACKAGING AND SHIPMENT 
Specimen Labeling for PBMC and All Tissue Samples 
This study will use both HTMCP specimen IDs and GlobalTrace labels during the screening 
process. 
With a black, water resistant, sharpie pen, label each GlobalTrace specimen label with the 
following information: 
• AMC Protocol #: AMC-083 
• AMC Subject ID#  
• Date and time of collection 
• Specimen type, i.e., PBMC, Fresh Frozen Biopsy, Tissue (block), Tissue (scrolls or H&E 
slides), Tissue (unstained slide) 
• Specimen purpose: Genomic Sequence Analysis, Central Pathology Review 
Shipment Preparation for PBMC Samples 
Reference Appendix III for the preparation of PBMC samples. 
• PBMC specimens should be shipped by overnight express on dry ice. Approximately 2 kg 
(4.4 lbs.) of dry ice pellets or chunks are needed for packaging samples. 

 
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• Specimens must be shipped on dry ice in a Styrofoam box, and then shipped in an outer 
cardboard box (required by FedEx). 
• Affix the FedEx airbill on blank side of the shipper making sure that it is marked “FedEx 
PRIORITY OVERNIGHT.” 
• Mark “OTHER” in the airbill under “Packaging.” Please refer to the Manual of Procedures 
and the AMC Operations website’s (www.AIDSCancer.org) Shipping tab for more 
information and the FedEx account details. 
• Under airbill section “Special Handling” indicate “YES-SHIPPERS DECLARATION 
NOT REQUIRED.” 
• Place “From/To” information onto areas provided on the shipper. 
• Make certain that shipper is already either pre-labeled with 
stamp, or make a 
paper label with 
 and affix it to the shipper. 
• Make certain that the net volume of the specimen being shipped is written in the space 
provided on the shipper or make a separate label with the volume in ml and affix to the 
shipper. 
• Affix airbill to shipper so that the ‘UN’ and ‘VOLUME’ labels are visible. 
• RETAIN THE TOP COPY OF THE AIRWAY BILL FOR YOUR RECORDS. 
• Place the box in the FedEx pickup area at your site or call to request a package pickup. 
Please Note: The shippers will be mailed back to each AMC site. 
***PLEASE DOUBLE CHECK PACKAGING OF SHIPPER AND DO NOT 
DEVIATE FROM REQUESTED LABELING. Shipping frozen aliquots requires the 
use of packaging acceptable for dry ice and Class 9 label with weight of dry ice written 
on package. 
Preparation of Snap Frozen Biopsy Tissue Samples for Shipment 
Tissue specimens to be fresh frozen should be placed in histowrap and then on dry ice 
immediately. The specimens may stay on dry ice until being transferred to a -80ºC freezer. 
Tissue specimens for donation may be batched for shipping after storage in -80ºC freezer.  
*NOTE: Specimens can only be accepted Monday through Friday. Therefore, specimens can 
only be shipped Sunday-Thursday for delivery the next day. Shipping frozen tissue requires 
the use of packaging acceptable for dry ice and Class 9 label with weight of dry ice written on 
package. 
Preparation of FFPE Tissue Block, Scrolls, or Slides for Shipment 
• Place the labeled tissue block or slides into a specimen container in bubble wrap or other 
adequate cushioning. Use sturdy outer packaging to prevent breakage. 
• Affix the FedEx airbill on blank side of the shipper. 
• Mark “OTHER” in the airbill under “Packaging.” 

 
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• Under airbill section “Special Handling” indicate “YES-SHIPPERS DECLARATION 
NOT REQUIRED.” 
• Please refer to the Manual of Procedures and the AMC Operations website’s 
(www.AIDSCancer.org) Shipping tab for the FedEx account details. Place “From/To” 
information onto areas provided on the shipper. Specimens are accepted MONDAY 
through THURSDAY only. FFPE tissue and slides should be shipped at ambient 
temperature by FedEx 2-day service to Dr. Silver at the address listed below. The tissue 
scrolls must be sent from the site to British Columbia Cancer Agency (BCCA) priority 
overnight (see item 6 below).  
• Make certain that shipper is visibly labeled “Exempt human specimen.” 
• RETAIN THE TOP COPY OF THE AIRWAY BILL FOR YOUR RECORDS. 
• Place the box in the FedEx pickup area at your site or call to request a package pickup. 
PBMC, FFPE block specimens, and pathology slides should be shipped to: 
Dr. Sylvia Silver 
George Washington University Medical Center 
2300 I Street, NW 
Ross Hall, Room 118 
Washington, DC 20037 
Phone: (202) 994-2945 
Fax: (202) 994-5056 
Email: ssilver@email.gwu.edu 
Technical Questions 
Contact Dr. Silver as noted above, or 
Razan Humeida (rhumeida@gwmail.gwu.edu, 202-994-3422), or 
Jonathan Lang (jlang13@gwmail.gwu.edu, 202-994-3422), or 
Sarah Fukui (sfukui@gwmail.gwu.edu, 202-994-3422) 
Preparation and Shipment of FFPE Tissue Scrolls 
In the absence of frozen tumor tissue, an FFPE block may be shipped to the BCCA 
following notification from the program office. If an FFPE block cannot be shipped, the 
following tissue scroll procedure can be used. 
• Cut a 4 µm slice and stain the slide with H&E stain as a top stain for pathology review 
• Measure length and width (in mm) of tissue specimen surface within paraffin block (see 
figure below) 
• Double click on excel table provided by the program office (available on AMC Operations 
web site among the AMC-083 protocol materials) to open editing function. 
(www.AIDSCancer.org) 
• Enter tumor length and width values measured in step b and cut the number of 10 
micrometer scrolls required to create 12mm3 is shown in yellow 

 
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• Put scrolls in tube for shipping (Eppendorf or cryovial) 
• Cut a 4 µm top slide and stain with H&E stain as a bottom slide for pathology review 
Ship tube of scrolls and the two H&E stained slides immediately to the BCCA at ambient 
temperature within 24 hours of cutting scrolls, via priority overnight service (with cold 
pack April-September). The BCCA must be informed of a shipment via email at least one 
day before shipment at the following email address: GSC_Submissions@bcgsc.ca 
BCCA Contact Information 
Biospecimen Administrator 
Cc: Dr. Andrew J. Mungall 
Genome Sciences Centre 
British Columbia Cancer Agency 
Suite 100 
570 W. 7th Avenue 
Vancouver, BC V5Z 4S6 
CANADA 
Phone: (604) 877-6088 
Email: GSC_Submissions@bcgsc.ca 
C. BILLING 
Please refer to the Manual of Procedures and the AMC Operations website’s 
(www.AIDSCancer.org) Shipping tab for the FedEx account details. It is only to be used for 
billing shipment of specimens to the lab where the sample is processed and/or stored. 
D. RECORD OF SPECIMENS 
This study will track specimens via GlobalTrace, a component of the AMC AdvantageEDC 
system. The GlobalTrace shipment manifest must accompany all specimen shipments. 
 
 

 
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APPENDIX V: PERFORMANCE STATUS SCALES 
Karnofsky Performance Scale 
ECOG Performance Status Scale 
Percent 
Description 
Grade 
Description 
100 
Normal, 
no 
complaints, 
no 
evidence of disease. 
0 
Normal activity. Fully active, able to 
carry on all pre-disease performance 
without restriction. 
90 
Able to carry on normal activity; 
minor signs or symptoms of 
disease. 
80 
Normal activity with effort; some 
signs or symptoms of disease. 
1 
Symptoms, 
but 
ambulatory. 
Restricted in physically strenuous 
activity, but ambulatory and able to 
carry out work of a light or sedentary 
nature (e.g., light housework, office 
work). 
70 
Cares for self, unable to carry on 
normal activity or to do active 
work. 
60 
Requires occasional assistance, 
but is able to care for most of 
his/her needs. 
2 
In 
bed 
<50% 
of 
the 
time. 
Ambulatory and capable of all self-
care, but unable to carry out any 
work activities. Up and about more 
than 50% of waking hours. 
50 
Requires considerable assistance 
and frequent medical care. 
40 
Disabled, requires special care and 
assistance. 
3 
In bed >50% of the time. Capable of 
only limited self-care, confined to 
bed or chair more than 50% of 
waking hours. 
30 
Severely disabled, hospitalization 
indicated. Death not imminent. 
20 
Very 
sick, 
hospitalization 
indicated. Death not imminent. 
4 
100% 
bedridden. 
Completely 
disabled. Cannot carry on any self-
care. Totally confined to bed or 
chair. 
10 
Moribund, 
fatal 
processes 
progressing rapidly. 
0 
Dead. 
5 
Dead.