Phase 1/2 Study of AMG 531 to Evaluate the Safety, Efficacy, and Pharmacokinetics in Patients With Aggressive Non-Hodgkin's Lymphoma Receiving R-HyperCVAD Alternating With R-Ara-C/MTX
Platelets are cells that help make the blood clot. A decrease in platelets can cause
bleeding, which may prevent or delay a patient from receiving chemotherapy. R-HyperCVAD
(rituximab, cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and R-Ara-C/MTX
(rituximab, cytarabine, and methotrexate) are two chemotherapy regimens that are known to
increase the risk of lower platelet counts. Researchers want to find out if AMG 531 can
lower the risk and severity of this side effect. AMG 531 is a protein that stimulates
Before you can start treatment on this study, you will have what are called "screening
tests." These tests will help the doctor decide if you are eligible to take part in the
study. You will have a complete medical history and physical exam, including measurement of
vital signs (temperature, pulse, breathing rate, and blood pressure). You will have blood
collected (about 3 teaspoons) for routine tests. Radiologic tests such as CT or MRI scans
will be done as needed. Women who are able to have children must have a negative blood
You will also have about 1 teaspoon of blood drawn to see if the you have antibodies to the
If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the toss of a coin) to one of four treatment groups. These 4 groups will also be
split into 2 separate subgroups (Arm A and Arm B). Participants in Arm A will either receive
AMG 531 or placebo on Day -5 (5 days before chemotherapy starts) and Day 5 (5 days after
chemotherapy starts). A placebo is a substance that looks like the study drug but which has
no active ingredients. Every 2 out of 3 participants in Arm A will receive AMG 531. One
out of every 3 participants in Arm A will receive placebo.
Participants in Arm B will receive either AMG 531 or placebo on Day 5 and 7. Every 2 out of
3 participants in Arm B will receive AMG 531. One out of every 3 participants in Arm B will
receive placebo. The dose of AMG 531 that participants in both Arms A and B receive will
depend on when they enroll on the study. There are 3 different dose levels of AMG 531 being
studied. Each new group of participants will receive a higher dose than the previous group.
All participants will receive treatment with R-HyperCVAD and R-Ara-C/MTX chemotherapy by
vein in alternating cycles. In Cycle 1, all participants will receive R-HyperCVAD by itself.
Each cycle is 3 weeks long.
Three (3) weeks later, in Cycle 2, all participants will receive either AMG 531 or placebo
following R-Ara-C/MTX. The AMG 531/placebo will be given as an injection under the skin on
Days -5 and 5 (Arm A) or on Days 5 and 7 (Arm B). After 2 cycles of treatment, based on
response of the disease and tolerance to the treatment, all participants may be able to
receive up to 4 more cycles of chemotherapy followed by AMG 531. For Cycles 3-6, you will
follow the same schedule of therapy as in the first 2 cycles. The dose of AMG 531 may be
increased at one time point during the study based on the response of the platelet counts.
Blood (about 1 teaspoon) will be collected for the evaluation of anti-AMG 531 antibody
status at the end of Cycles 2 and 4. You will be taken off the study if your disease gets
worse or intolerable side effects occur. The number of blood tests drawn will depend on your
clinical condition. These samples (about 1 teaspoon each) will be taken at least 2 times a
week and as often as once a day during anticipated periods of low blood cell counts.
At the end of the study, you will have an interim medical history and physical exam,
including measurement of vital signs. You will have blood (about 1 teaspoon) drawn for
routine end-of-study analysis. Blood (about 1 teaspoon) will also be collected for the
evaluation of anti-AMG 531 antibody status.
This is an investigational study. R-HyperCVAD and R-Ara-C/MTX are commercially available
chemotherapy drugs. AMG 531 is not FDA approved or commercially available. At this time,
AMG 531 is being used in this study for research purposes only. About 36 evaluable patients
(maximum of 50 patients) will take part in this study. All will be enrolled at M. D.
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Highest maximum dose of AMG 531 given to treat thrombocytopenia (low platelet counts) in patients who have received chemotherapy
Continual reassessment method with each 3 week cycle
Saroj Vadhan-Raj, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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