Clinical trial NCT02042950
Conditions: Lymphoma
Keywords: Lymphoma Mantle Cell Lymphoma MCL Relapsed Refractory Carfilzomib
Sponsor: M.D. Anderson Cancer Center
Start date: 2014-07-14; Completion date: 2017-12-20
Enrollment: 6 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of this clinical research study is to learn if carfilzomib can help control relapsed or refractory MCL. The safety of this drug will also be studied.

Detailed description:
Study Drug Administration:

If participant is found to be eligible for this study, they will begin the first cycle of treatment with carfilzomib. Each cycle is 28 days.

On Days 1, 2, 8, 9, 15, and 16 of Cycles 1-12:

* Participant will receive carfilzomib by vein over 30 minutes. The first 2 doses participant receives may be lower than later doses. This is to reduce the risk of an allergic reaction.

On Days 1, 2, 15, and 16 of Cycles 13 and beyond:

* Participant will receive carfilzomib by vein over 30 minutes.

Participant should drink at least 6-8 cups (8 ounces each) of fluid per day starting 2 days before their first day of treatment and for as long as their doctor asks them to. During Cycles 1 and 2, participant will receive fluids by vein before and after their dose of carfilzomib.

Before participant receives carfilzomib, they will be given standard drugs (such as allopurinol, dexamethasone, antibiotics, anti-fungals, and/or anti-virals) to help decrease the risk of side effects. Participant may ask the study staff for information about how the drugs are given and their risks.

When participant receives the drugs during Cycle 1 and on Day 1 of Cycle 2, they will be monitored for side effects for 1 hour after they receive the study drug.

Study Visits:

On Day 1 of all cycles:

* Participant will have a physical exam.
* Participant will have a neurological exam to check for weakness, numbness and pain in their hands and feet.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* If participant's doctor thinks it is needed, they will have a bone marrow biopsy and/or aspiration to check the status of the disease.
* If participant's doctor thinks it is needed, they will have an ECHO or a MUGA.
* If participant is able to become pregnant, they will have a blood (about 1½ tablespoons) or urine pregnancy test. (Cycles 2 and beyond only)

On Days 2, 9, and 16 of all cycles:

* Participant's vital signs will be measured.

On Days 8 and 15 of all cycles:

* Participant will have a physical exam.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* If participant is able to become pregnant, they will have a blood (about 1½ tablespoons) or urine pregnancy test.

On Day 1 of Cycles 2, 4, 6, and so on up to Cycle 12, then every 3 cycles after that:

* If the study doctor thinks it is needed, participant will have a CT scan, MRI, PET scan, and/or PET/CT scan to check the status of the disease.
* If the study doctor thinks it is needed, participant will have a gastrointestinal endoscopy or colonoscopy.

Length of Study:

Participant may continue taking the study drug for up to 3 years. Participant will no longer be able to take the drug if the disease gets worse, if intolerable side effects occur, or if they are unable to follow study directions.

Patient's participation on the study will be over once they have completed the long term follow-up phone calls.

End-of-Treatment Visit:

Within about 30 days, after participant finishes taking the study drug they will return to the clinic for the following tests and procedures:

* Participant will have a physical exam.
* Participant will have a neurological exam to check for weakness, numbness and pain in their hands and feet.
* Participant will have an EKG to check their heart function.
* Blood (about 3-5 tablespoons) will be drawn for routine tests and to check the status of the disease.
* Participant will have a CT scan and/or x-ray to check the status of the disease.
* Participant will have a PET/CT scan to check the status of the disease.
* If participant's doctor thinks it is needed, they will have a bone marrow biopsy and aspiration
* If participant's doctor thinks it is needed, they will have a colonoscopy/gastrointestinal endoscopy.
* If participant is able to become pregnant, they will have a blood (about 1½ tablespoons) or urine pregnancy test.

Long Term Follow-Up:

After participant's end-of-treatment visit, they will be called every 6 months for 1 year to see how they are doing and to find out about any other treatments they have received since they stopped study treatment. These calls will take about 2-3 minutes. In addition to the phone calls, participant's medical records may be reviewed as well.

This is an investigational study. Carfilzomib is FDA approved and commercially available for the treatment of certain types of multiple myeloma. This drug is investigational for the treatment of MCL.

Up to 60 participants will be enrolled on this study. All will be enrolled at MD Anderson.

Arms: arm 1: Carfilzomib given at a dose of 20\*/56 mg/m\^2 (\* CFZ 20 mg/m2 by vein on Days 1 and 2 in Cycle 1 followed by 56 mg/m\^2 for each subsequent dose thereafter) on days 1 and 2, 8 and 9, 15 and 16 of a 28-day cycle (following cycle 12 carfilzomib given on days 1 and 2 and 15 and 16 only).
Interventions: intervention 1: Carfilzomib
Intervention descriptions: intervention 1: Starting dose: 20 mg/m2 by vein on Days 1 and 2 in Cycle 1 followed by 56 mg/m\^2 for each subsequent dose thereafter) on days 1 and 2, 8 and 9, 15 and 16 of a 28-day cycle (following cycle 12 carfilzomib given on days 1 and 2 and 15 and 16 only).

Protocol documents:
Prot_SAP_000.pdf: 
2013-0259
January 21, 2016
Abstract Page 1
Protocol Abstract Page
A Phase II Study of Carfilzomib in the Treatment of Relapsed/Refractory 
Mantle Cell Lymphoma
2013-0259
Core Protocol Information
Study Chairman: 
Hun J. Lee
Department:
Lymphoma/Myeloma
Phone:
713-792-2860
Unit:
429
Full Title: 
A Phase II Study of Carfilzomib in the Treatment of Relapsed/Refractory Mantle Cell 
Lymphoma
Protocol Phase:
Phase II
Version Status:
Terminated 12/21/2017
Version:
09
Document Status:
Final
Abstract
Objectives:
PRIMARY OBJECTIVE: 
To evaluate the efficacy of single agent carfilzomib in patients with relapsed/refractory MCL 

as measured by response rate.
To further evaluate the toxicity of Carfilzomib in patients with MCL.

SECONDARY OBJECTIVES:
To estimate the response duration, progression free survival, time to failure and overall 

survival. 
Rationale: (Be as concise as possible)
Study Rationale
MCL is a distinct subset of B-cell non-Hodgkin’s lymphoma (NHL) characterized by the t (11, 
14) chromosomal translocation, which results in over-expression of cyclin D1 and deregulation 
of the cell cycle. MCL is not yet curable because most patients eventually relapse and succumb 
to progressive MCL. Therefore, novel therapeutic strategies are needed for the treatment of 
patients with MCL. 
Carfilzomib, an irreversible proteasome inhibitor with selectivity for the chymotrypsin-like 


2013-0259
January 21, 2016
Abstract Page 2
active site, inhibits the proliferation of human tumor cells. In our laboratories, carfilzomib 
induced apoptosis of both established MCL cells and fresh primary MCL cells from patients in a 
dose-dependent manner. Carfilzomib significantly inhibited the growth of subcutaneous tumors 
and prolonged the long-term survival of the MCL-bearing SCID mice. Therefore, Carfilzomib is 
effective in vitro and in vivo in preclinical studies.35,36 
Based on the above data and observations, we propose the current LOI for a phase II clinical trial 
using carfilzomib in relapsed refractory MCL.  We hypothesize that this agent may result in a 
high CR and PR response rates and have significantly reduced side effects.  This protocol aims 
to evaluate the safety of carfilzomib as single agent in patients MCL and to observe the response 
rate to this regimen.   
Eligibility: (List All Criteria)
Inclusion:
1)
Confirmed diagnosis of mantle cell lymphoma.
2)
Patients must have relapsed or refractory MCL.
3)
Understand and voluntarily sign an IRB-approved informed consent form.
4)
Age >/= 18 years at the time of signing the informed consent.
5)
Patients must have bi-dimensional measurable disease (bone marrow only involvement is 
acceptable).
6)
Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
7)
Serum bilirubin <1.5 mg/dl and Creatinine Clearance >/= 30 mL/min, platelet count >50,000/mm^3 
and absolute neutrophil count (ANC) > 1,000/mm^3. [Patients who have bone marrow infiltration by MCL 
are eligible if their ANC is · 500/mm^3 (growth factor allowed) or their platelet level is equal to or > than 
30,000/mm^3.]. AST (SGOT) and ALT (SGPT) < 2 x upper limit of normal or < 5 x upper limit of normal if 
hepatic metastases are present. Uric acid within normal limits.
8)
Females of childbearing potential (FCBP)* must have a negative serum or urine pregnancy test 
within 30 days of initiation of therapy. * A female of childbearing potential is a sexually mature woman 
who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally 
postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 
consecutive months).
9)
FCBP must agree to use a highly-effective form of birth control while taking the study drug and for 1 
month after the last dose of study drug. Highly-effective forms of birth control include implants, 
injectables, birth control pills with 2 hormones, some intrauterine devices (IUDs), or having a sterilized 
partner. The type of birth control used must be discussed with and approved by the attending physician 
prior to initiation of study drug.
10)
Males must agree to use a condom with spermicide every time they have sex during the study and 
for 3 months after the last dose of study drug. They also must agree to not donate sperm during the study 
and for 3 months after the last dose of study drug.
11)
Patients must be willing to receive transfusions of blood products.
Exclusion:


2013-0259
January 21, 2016
Abstract Page 3
1)
Any serious medical condition including but not limited to, uncontrolled hypertension, uncontrolled 
diabetes mellitus, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease 
(COPD), renal failure, active hemorrhage, or psychiatric illness that, in the investigators opinion places 
the patient at unacceptable risk and would prevent the subject from signing the informed consent form.
2)
Pregnant or breast feeding females.
3)
Known HIV infection. Patients with active hepatitis B infection (not including patients with prior 
hepatitis B vaccination; or positive serum Hepatitis B antibody). Known hepatitis C infection is allowed as 
long as there is no active disease and is cleared by GI consultation
4)
All patients with active central nervous system lymphoma.
5)
Significant neuropathy (Grades 3 - 4, or Grade 2 with pain) within 14 days prior to enrollment.
6)
Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib).
7)
Contraindication to any of the required concomitant drugs or supportive treatments or intolerance to 
hydration due to preexisting pulmonary or cardiac impairment including pleural effusion requiring 
thoracentesis to ascites requiring paracentesis.
8)
Patients with active pulmonary embolism or deep vein thrombosis (diagnosed within 30 days of 
study enrollment).
9)
Patients with symptomatic bradycardia (heart rate < 50 bpm, hypotension, light-headedness, 
syncope).
10)
Use of any standard/experimental anti-lymphoma drug therapy, including steroids, within 3 weeks 
of initiation of the study or use of any experimental non-drug therapy (e.g. donor leukocyte/mononuclear 
cell infusions) within 56 days of initiation of the study drug treatment. Prior allogeneic SCT within 16 
weeks or autologous SCT within 8 weeks of initiation of therapy.
11)
Patients with New York Health Association (NYHA) Class III and IV heart failure, myocardial 
infarction in the preceding 6 months, and conduction abnormalities, including but not limited to atrial 
fibrillation, atrioventricular (AV) block block, QT prolongation, sick sinus syndrome, ventricular 
tachycardia, as these patients may be at greater risk for cardiac complication, per carfilzomib labeling.
12)
The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a 
greater risk to the patient’s health and survival, than of the MCL, within the subsequent 6 months at the 
time of consent. Investigator discretion is allowed.
13)
Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 
days prior to enrollment.
14)
Patients who have received any previous Carfilzomib treatment.
Are patients <18 years of age eligible to participate in this study?  
Yes
No
Studies that include children must meet the criteria for inclusion.
http://www.fda.gov/ohrms/dockets/AC/04/briefing/4028B1_05_NIH-Inclusion%20of%20Children.doc
http://www.hhs.gov/ohrp/policy/populations/children.html
Studies that exclude children must have appropriate justification.  Please select all that 
apply:


2013-0259
January 21, 2016
Abstract Page 4
Phase I or Phase II study targeting cancer that is very unusual in pediatrics (e.g., prostate, lung, 
breast, chronic lymphocytic leukemia, etc.)
Are participants >65 years of age eligible to participate in this study?  
Yes
No
Are pregnant women eligible to participate in this study?
Yes
No
Will the recruitment population at M. D. Anderson include persons who are incarcerated at time of 
enrollment (e.g., prisoners) or likely to become incarcerated during the study?
Yes
No
Disease Group:
Lymphoma
Treatment Agents/Devices/Interventions:
Carfilzomib
Proposed Treatment/Study Plan:
Is treatment assignment randomized?
Yes
No
Is this a blinded or double-blinded study?
Yes
No
This will be a single-center, phase II clinical trial in patients with relapsed refractory mantle cell 
lymphoma. 
Carfilzomib will be given at a dose of 20*/56 mg/m^2 (* CFZ 20 mg/m2 IV on Days 1 and 2 in 
Cycle 1 followed by 56 mg/m^2 for each subsequent dose thereafter) on days 1 and 2, 8 and 9, 
15 and 16 of a 28-day cycle (following cycle 12 carfilzomib will be given on days 1 and 2 and 
15 and 16 only).  The targeted enrollment according to our statistical design is 60 patients.
All patients shall be registered with CORe (Clinical Oncology Research System) at (713) 
745-2673 prior to receiving therapy.
Carfilzomib will be administered intravenously (IV) at 20/56 mg/m
2.
Overall response rate (ORR) (> partial response [PR]) will be assessed by the Revised Response 
Criteria for Malignant Lymphoma, with secondary assessment of clinical benefit response (CBR 
= minimal response [MR] + ORR), time to progression (TTP), and duration of response (DOR).
Therapy will continue in 28-day cycles for a maximum of 36 cycles (3 years), until there is 
disease progression, unacceptable toxicity or the patient chooses to withdraw from therapy. 
All patients will be asked to record the medications they take at home and to bring the 
medication record they use to the clinic with them when they return to see their physician or 


2013-0259
January 21, 2016
Abstract Page 5
research nurse.  The patients will be provided with a specific medication form on which to 
record this information.  Patients will also be asked to report any adverse events they experience 
during the course of the study.  They will be given a form on which to record their information 
and this form will be returned on their next clinic visit to assist the research personnel in 
determining adverse events.
Carfilzomib for Injection is supplied as a lyophilized parenteral product in single-use vials. The 
lyophilized product is reconstituted with Water for Injection to a final carfilzomib concentration 
of 2.0 mg/mL prior to administration.  
Table of Assessments


2013-0259
January 21, 2016
Abstract Page 6
Study Enrollment:
The study population for this research will consist of participants from:
Only at MDACC
Estimated Accrual:
Total Accrual at MDACC:
60
Estimated monthly accrual at MDACC:
1-2
Accrual Comments:
 
Is this an NCI-Cancer Therapy Evaluation Protocol (CTEP)?
No
Is this an NCI-Division of Cancer Prevention Protocol (DCP)?
No
Statistical Considerations:
The primary objective for this phase II study is to estimate the efficacy and evaluate the toxicity 


2013-0259
January 21, 2016
Abstract Page 7
of the single agent Carfizomib when given to patients with relapse/refractory mantle cell 
lymphoma (MCL). The maximum number of patients will be enrolled is 60.  
The overall response (OR: complete response + partial response) at 4 cycles and toxicity at 1 
cycle will be monitored simultaneously using the Bayesian stopping boundaries calculated based 
on beta-binomial distribution.  Independence is assumed between OR and toxicity.  Toxicity is 
defined as the following toxicities observed during cycle 1 (28 days) of the treatment:
Non-hematologic:
>/= Grade 2 neuropathy with pain

>/=Grade 3 non-hematologic toxicity (excluding nausea, vomiting, diarrhea, hyperglycemia 

due to dexamethasone treatment and rash due to lenalidomide treatment)
>/=Grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal 

therapy
>/=Grade 4 fatigue persisting for  > 7 days

Treatment delay greater than 21 days for toxicity

Hematologic:

Grade 4 neutropenia [absolute neutrophil count (ANC) < 500/mm3] lasting for > 7 days

Febrile neutropenia (ANC < 1,000/mm3 with a fever >/=38.3·C)
Grade 4 thrombocytopenia (<25,000/mm3) that persists for >/= 7 days, despite holding treatment
Treatment delay greater than 21 days for toxicity
Patients will be monitored by a cohort size of 10 according to the following stopping boundaries 
for OR at 4 months and toxicity at one month.  If the number of responses required for moving 
the trial to next stage has not been achieved, the patient enrollment will be halted until enough 
responses observed.


2013-0259
January 21, 2016
Abstract Page 8
The operating characteristics are summarized in the following tables (based on simulations from 
10,000 trials).


2013-0259
January 21, 2016
Abstract Page 9
The above stopping boundaries and operating characteristics are calculated using MultcLean (v.2.0.0) 
design software downloaded from http://biostatistics.mdanderson.org/SoftwareDownload.  A sample 
size of 1000 was used for the historical (standard treatment) data for the Model Input to approximate 
the fix targets for OR and toxicity rates.  
Summary statistics will be provided for continuous variables.  Frequency tables will be used to 
summarize categorical variables.  Logistic regression will be utilized to assess the effect of 
patient prognostic factors on the response rate and the toxicity rate.  The distribution of 
time-to-event endpoints including overall survival and progression free survival will be 
estimated using the method of Kaplan and Meier.  Comparison of time-to-event endpoints by 
important subgroups will be made using the log-rank test.  Cox proportional hazard regression 
will be employed for multivariate analysis on time-to-event outcomes.
Toxicity data will be summarized by frequency tables for all patients.  For the efficacy 
endpoints, intend-to-treat analysis will be applied to the eligible patients.  For the toxicity 
endpoint, per-treated analysis will be performed to include any patient who received the 
treatment regardless of the eligibility nor the duration or dose of the treatment received. 
Data Safety Monitoring Board / DSMB at MDACC:
Select the name of the data safety monitoring board (DSMB) monitoring this protocol:
Not Applicable
Please explain:
This protocol is not randomized or blinded.
Protocol Monitoring:
Does this protocol have a schedule for interim and final analysis?
Yes
Provide a summary or schedule of interim analysis.
Patients will be monitored by a cohort size of 10 according to the following stopping boundaries 
for OR at 4 months and toxicity at one month.  If the number of responses required for moving 
the trial to next stage has not been achieved, the patient enrollment will be halted until enough 
responses observed.


2013-0259
January 21, 2016
Abstract Page 10
Number of patients evaluated
Stop if  </= OR observed
Stop if >/= toxicity 
observed
10
1
6
20
5
10
30
8
14
40
12
18
50
16
21
60
Always stop with this many 
patients
Protocol Monitoring Plan:
This study will be monitored by the MD Anderson IND Office and a protocol‐specific monitoring plan will 
be followed. 
Intellectual Property:
1.
Does this study include any agents, devices, or radioactive compound (or 
drug) manufactured at  MD Anderson Cancer Center or by a contract 
manufacturer?
No
Investigational New Drugs (IND):
Does this protocol require an IND?
Yes
Who is the IND Holder/Regulatory Sponsor?
MD Anderson Cancer Center
IND Number:
116699
Please "Compose" an Investigator’s Brochure Cover Letter.  For technical assistance, contact the PDOL 
Help Desk, 713-745-7365.
Investigational Device (IDE):
Does this study utilize an Investigational Device?
N/A
Sponsorship and Support Information:
Does the Study have a Sponsor, Supporter or Granting Agency?
Yes


2013-0259
January 21, 2016
Abstract Page 11
Sponsor Name:
Onyx
Support Type:
Industry Funding
Agent Name(s): Carfilzomib
This Sponsor/Supporter/Granting Agency will receive data.
Radioactive Material:
Does this study involve the administration of radioisotopes or a
radioisotope labeled agent?
Click here  for help
N/A
Biosafety:
Does this study involve the use of Recombinant DNA Technology? 
No
Does this study involve the use of organisms that are infectious to humans?
No
Does this study involve human/animal tissue other than blood derived 
hematopoietic stem cells?
N/A
Questions should be addressed to the Transfusion Medicine Tissue Coordinator at 713-792-8630.
Laboratory Tests:
Is there any biomarker testing in this study being used to determine patient/participant eligibility, 
treatment assignment, or management of patient/participant care?
Yes
No
Not Applicable For This Protocol
Manufacturing:
Will you manufacture in full or in part (split manufacturing) a drug or biological 
product at the M. D. Anderson Cancer Center for the proposed clinical study?
No
Student/Trainee Information:
Is this research being conducted as a partial fulfillment for completion of a degree?
No