Clinical trial NCT01326728: Relapsed Malignant Blood Cancer After Allogeneic Hematopoietic Stem Cell Transplantation
Official title: Study of the Biology and Natural History of Disease Outcomes in Patients Treated With Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Chronic Myelogenous Leukemia
Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Hodgkins Lymphoma
Non-Hodgkins Lymphoma
Keywords: Relapse
Hematologic Malignancy
Allogeneic
Hematopoietic Stem Cell Transplantation
Leukemia
Lymphoma
Hodgkin Lymphoma
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2011-03-31
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals aged 18-99 who are being enrolled on Clinical Center protocols to undergo allotransplant therapy for hematologic malignancies. The population will consist of those that have received allotransplant treatment for hematologic malignancy, are in remission either at or after Day 100, have malignancy progression or persistently stable disease post allotransplant, or the related donor of eligible allotransplant recipients.

Brief summary: Background:

Allogeneic hematopoietic stem cell transplantation (or allotransplant; donor blood stem cells) have been used with varying degrees of success as an immune therapy for blood-system cancers (leukemias, myelodysplastic syndrome, lymphomas, multiple myeloma, etc.). Some people s cancer remains active (comes back or continues to spread) after an allotransplant, while other peoples cancer disappears and they are hopefully cured. National Institutes of Health (NIH) researchers are studying the reasons for these different treatment outcomes, and trying to develop better cancer treatments for people with active cancer after allotransplant. Researchers are collecting data from people who have had allotransplants for a cancer of the blood, whether or not the cancer is in remission, and from their donors. Those with active cancers may be eligible to participate in one of several NIH studies testing treatments for active cancer after allotransplant.

Objectives:

* To develop a systematic, comprehensive evaluation of individuals with relapsed malignant blood cancers after allotransplant (and, if available, their donors) to identify potential treatment study options
* To compare the immune system after allotransplant between people whose cancers are growing with people whose cancers remain in remission.
* To compare the immune system after cancer relapse/progression treatment between people whose cancer responds to treatment with those whose cancers continue to grow.

Eligibility:

* Individuals whose blood system cancer grows or comes back after receiving allotransplant treatment.
* Individuals whose blood system cancer is responding or in remission 100 days or more after receiving allotransplant treatment.
* Related stem-cell donors of eligible allotransplant recipients.

Design:

* Participants will be evaluated with a full physical examination, detailed medical history (for recipients, including a history of allotransplant treatment process, side-effects, etc.), and blood tests. Recipients will also have imaging studies, possible tissue biopsies, quality of life questionnaires/assessments, and other tests to evaluate the current state of their cancer, whether active or in remission. In some cases, it may be possible to substitute results from recent tests and/or biopsies.
* Healthy related donors will have apheresis to provide white blood cells for study and/or for use in potential treatment options. If stem cells would be medically helpful to a recipient, their donors might be asked to take injections of filgrastim before the apheresis procedure to stimulate the production of stem cells for collection.
* As feasible, all recipients will be asked to return to the NIH for detailed follow-up visits in conjunction with 6, 12, and 24 months post-allotransplant evaluations, and may be monitored between visits.
* Recipients whose cancers are active and who are found to be eligible for treatment protocols at the NIH will continue to be monitored on this study while participating on treatment protocols. Return visits and follow-up tests for this study will be coordinated with those required by the treatment protocol.
* Participants may return in the future to be evaluated for new treatment study options (recipients) or additional cell donations for therapy (donors).

Detailed description: Background:

* Cancer relapse is a significant clinical problem following allogeneic hematopoietic stem cell transplantation (allotransplant), affecting up to half of all patients. Effective treatment options are extremely limited and, for most cancers, rarely curative.
* Several Clinical Center (CC) protocols are evaluating treatment for post-allotransplant relapse. Relapse often progresses quickly; patients require rapid assessment of protocol options in order to expedite initiation of treatment.
* Basic information is needed to improve management of relapse after allotransplant clinical information regarding risk of relapse and cancer behavior after allotransplant, and information on the biology of relapse after allotransplant in order to identify risk factors, target prevention strategies, detect early relapse and develop effective treatments.

Objectives:

Primary Objective:

To provide a mechanism for systematic, comprehensive evaluation of individuals with relapsed hematologic malignancy after allotransplant and, if available, their donors, to streamline identification of protocol options, enrollment and initiation of therapy.

Eligibility:

1. Individuals who have received allotransplant treatment for hematologic malignancy ("Recipient-Subjects"). Analyses (secondary aims) will consider two comparison cohorts:

   1. Relapse Cohort: Cancer progression, relapse or persistently stable (unremitting) disease
   2. Remission (Control) Cohort: Cancer response or remission at/after Day 100
2. Individuals who are being enrolled on Clinical Center protocols to undergo allotransplant therapy for hematologic malignancies and are being evaluated at the Clinical Center for planned allotransplantation. (Recipient-Subjects)
3. Related donors of eligible allotransplant recipients ("Donor-Subjects")

Design:

1. Recipient-Subjects will have clinical and research evaluations at baseline and three and six months post-allotransplant, at six-month intervals through three years post-allotransplant, then yearly. Evaluation after relapse treatment response and for new protocol options is permitted.
2. Donor-Subjects will be enrolled at the time of their clinical evaluation and cell collection for Recipient-Subject therapy. Return evaluation for additional clinical product collection is permitted.
3. Accrual Ceiling: 500 consented subjects (350 Recipient-Subjects and 150 Donor-Subjects) over 5 years, averaging 70 Recipient-Subjects and 30 Donor-Subjects enrolled per year.

Eligibility criteria: * INCLUSION CRITERIA:

RECIPIENT SUBJECTS:

1. Individuals who are candidates for allotransplant therapy for hematologic malignancies and are being evaluated at the Clinical Center for planned allotransplantation.
2. Individuals who have received allotransplant treatment for hematologic malignancy and have:

   1. Hematologic recovery after allotransplant: e.g., have had neutrophil recovery to 500 cells/mcL. Secondary cytopenias or cytopenias due to disease progression will be permitted. Note: this requirement will not apply to subjects enrolling pre-transplant, i.e, who receive transplant-related medical care at the Clinical Center (CC).
   2. An ongoing relationship with a primary oncologist who will continue to provide continuity of care during and after study participation.
   3. Following record review and information exchange between the patients primary oncologist and the National Cancer Institute (NCI) Principal Investigator (PI)/Designee, the PI/Designee determines that the individual reasonably could be expected to safely tolerate travel to and from the Clinical Center (CC) to undergo evaluation as defined in the protocol, in the event that the patient is ineligible or uninterested in participating in open treatment protocols.
3. 18-99 years.
4. Ability of subject to understand and the willingness to sign a written informed consent document.

DONOR SUBJECTS:

1. Individuals who are/will be the donors of allogeneic hematopoietic stem cell transplants received by Recipient-Subjects who are to be enrolled on this protocol.
2. Age 18-99 years.
3. Ability of the subject to understand and the willingness to sign a written informed consent document.
4. Individuals with evidence of infection with transfusion-transmittable agents (Hepatitis B and C Viruses (HBV, HCV); Human Immunodeficiency Virus (HIV (Omega)), Human TLymphotrophic Virus (HTLV I/II), West Nile Virus (WNV) and Trypanosoma cruzi) will not be excluded from study participation. However, Donor-Subjects with evidence of HIV infection will only be able to donate cells for research. Donors with a history of HBV or HCV infection will be able to donate for research, and may be eligible to donate for therapeutic administration. However, determination of permissibility for clinical donation will require a hepatology consultation and the consent of the intended recipient after discussion of the risk/benefit of the donor cell product and the possibility/consequences of transmission. The PI/Designee will make the final determination of permissibility of donation for recipient cell therapy.

6. Unrelated donor selection will be in accordance with the National Marrow Donor Program (NMDP) standards. When a potentially eligible recipient of an unrelated donor product from an NMDP Center is identified, the recipient will complete an NMDP search transfer request to allow NIH NMDP staff to contact the NMDP Coordinating Center, who will, in turn, contact the donors prior Donor Center. The NMDP Policy for Subsequent Donation Requests will be followed and the appropriate forms (Subsequent Donation Request Form and Therapeutic T Cell Collection Prescription Form) will be submitted as required.

EXCLUSION CRITERIA:

RECIPIENT SUBJECTS:

1. Individuals with rapid disease progression or aggressive cancer histology who, in the opinion of the PI/Designee, require urgent therapy within 30 days in order to preserve organ function or quality of life. This restriction will not apply if there is no approved therapy with a reasonable chance of disease response, if the patient does not have access to an effective therapy and the patient appears to be eligible for an accruing CC treatment protocol or if the patient is enrolled on an NIH/CC clinical protocol, e.g., allotransplant protocol.
2. Pregnancy or lactating. Additionally, Recipient-Subjects of childbearing potential that will receive cancer treatment under this protocol must be willing to use an effective method of contraception.

DONOR SUBJECTS:

1. Adult donors who are not eligible for clinical donation will not be excluded from study participation, but will only be able to donate cells for research.

Primary outcomes:
measure: Immune Suppression
timeFrame: up to 100 days or more following transplant
measure: Time to Progression After Allotransplant
timeFrame: first day of treatment to day 100 after allotransplant
measure: Overall Survival
timeFrame: first day of treatment to the day of death
measure: Days to Engraftment
timeFrame: up to 100 days or more following allotransplant
measure: Count of Participants With Acute Graft Versus Host Disease (GVHD) Grade 2 or More 100 Days Post Allotransplant
timeFrame: 100 days or more post allotransplant
measure: Count of Participants With Chronic Graft Versus Host Disease (GVHD) Grade 2 or More 100 Days Post Allotransplant
timeFrame: 100 days post allotransplant
measure: Count of Participants With Infection After Allotransplant
timeFrame: up to 100 days or more post allotransplant
Secondary outcomes:
measure: Number of Participants With Serious and Non-Serious Adverse Events
timeFrame: 5 years
Other outcomes:
measure: Count of Participants With Clinical Blood Markers of Inflammation
timeFrame: up to 100 days or more following allotransplant
measure: Regimen-Specific Sensitivity After Allotransplant
timeFrame: up to 100 days or more following allotransplant
measure: Tumor Immune Response Graft-Versus-Leukemia (GVL)
timeFrame: up to 100 days or more following allotransplant
measure: Relapse After Day 100 or Following Treatment of Graft Versus Host Disease (GVHD)
timeFrame: After Day 100 or Following Treatment of GVHD
measure: Recovery of Clinical Immunity After Allotransplant
timeFrame: up to 100 days or more following allotransplant
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Ronald E Gress, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pavletic SZ, Kumar S, Mohty M, de Lima M, Foran JM, Pasquini M, Zhang MJ, Giralt S, Bishop MR, Weisdorf D. NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: report from the Committee on the Epidemiology and Natural History of Relapse following Allogeneic Cell Transplantation. Biol Blood Marrow Transplant. 2010 Jul;16(7):871-90. doi: 10.1016/j.bbmt.2010.04.004. Epub 2010 Apr 24.
citation: Dazzi F, Fozza C. Disease relapse after haematopoietic stem cell transplantation: risk factors and treatment. Best Pract Res Clin Haematol. 2007 Jun;20(2):311-27. doi: 10.1016/j.beha.2006.10.002.
citation: Porter DL, Alyea EP, Antin JH, DeLima M, Estey E, Falkenburg JH, Hardy N, Kroeger N, Leis J, Levine J, Maloney DG, Peggs K, Rowe JM, Wayne AS, Giralt S, Bishop MR, van Besien K. NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2010 Nov;16(11):1467-503. doi: 10.1016/j.bbmt.2010.08.001. Epub 2010 Aug 10.