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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

Phase 1/Phase 2
18 Years
Not Enrolling

Thank you

Trial Information

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
platelet production.

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
pregnancy test.

You will also have about 1 teaspoon of blood drawn to see if the you have antibodies to the
study drug.

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.

Inclusion Criteria:

1. Patients with a diagnosis of previously untreated aggressive non-Hodgkin's lymphoma,
including patients with mantle cell lymphoma, who will be or are receiving treatment
with R-HyperCVAD and R-Ara-C/MTX. Patients in whom Rituximab is not used, due to
contraindication, will be eligible. Patients whose therapy was switched to
(R)Hyper-CVAD after initial treatment with (R)CHOP, because of aggressive disease
will also be eligible for the study.

2. Patients age >/= 18 years.

3. Karnofsky Performance Scale >/= 70.

4. Adequate hematologic (ANC >/= 1000/mm(3), platelet count >/= 100,000/mm(3) and Hgb
>/= 8gm/dL), renal (serum creatinine < 2mg/dL), and hepatic functions (total
bilirubin glutamate oxaloacetate transaminase (SGOT) respective normal range).

5. Patients (male and female) with childbearing potential (defined as not
post-menopausal for 12 months or no previous surgical sterilization) must use
adequate birth control.

6. Institutional Review Board (IRB)-approved signed informed consent.

Exclusion Criteria:

1. Pregnant or lactating women.

2. History of Central Nervous System (CNS) involvement.

3. Co-morbid medical or psychiatric illnesses that preclude treatment with intense dose

4. Patients with history of deep vein thrombosis (DVT) or pulmonary embolus.

5. History of any platelet disorders including Idiopathic thrombocytopenic purpura
(ITP), Thrombotic thrombocytopenic purpura (TTP) or bleeding disorders.

6. Prior surgery or Radiation Therapy (RT) within 2 weeks of study entry.

7. Patients with significant cardiac disease (New York Heart Association (NYHA) Class
III or IV), dysrrhythmia, or recent history of myocardial ischemia (MI) or ischemia,
transient ischemic attack or cerebrovascular accident (CVA) within the previous 6
months of study entry.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

Highest maximum dose of AMG 531 given to treat thrombocytopenia (low platelet counts) in patients who have received chemotherapy

Outcome Time Frame:

Continual reassessment method with each 3 week cycle

Safety Issue:


Principal Investigator

Saroj Vadhan-Raj, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

March 2006

Completion Date:

April 2012

Related Keywords:

  • Lymphoma
  • Non-Hodgkin's Lymphoma
  • Lymphoma
  • Mantle Cell Lymphoma
  • AMG 531
  • Romiplostim
  • Placebo
  • R-HyperCVAD
  • R-Ara-C/MTX
  • Cyclophosphamide
  • Cytarabine
  • Dexamethasone
  • Doxorubicin
  • Methotrexate
  • Rituximab
  • Vincristine
  • Decadron
  • Neosar
  • AD
  • Hydroxydaunomycin hydrocholoride
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
  • Lymphoma
  • Lymphoma, Non-Hodgkin



UT MD Anderson Cancer Center Houston, Texas  77030