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Study of AMG 531 to Evaluate the Safety & Efficacy in Patients With Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00299182
First received: March 3, 2006
Last updated: March 8, 2013
Last verified: March 2013
History of Changes
  Purpose

The goal of this clinical research study is to find the highest safe dose of AMG 531 that can be given to treat thrombocytopenia (low platelet counts) in patients who have received chemotherapy. Researchers will also look at the safety and effectiveness of AMG 531.

Primary Objectives:

  1. To determine the clinical safety and tolerability of AMG 531 administered following chemotherapy (R-HyperCVAD alternating with R-Ara-C/MTX) in patients with non-Hodgkin's lymphoma.
  2. To determine an optimal biologic dose (OBD) of AMG 531 in patients receiving R-HyperCVAD and R-Ara-C/MTX.
  3. To evaluate the effects of AMG 531 on the degree and duration of thrombocytopenia and platelet recovery following chemotherapy(chemo).

Secondary Objectives:

1. To evaluate limited pharmacokinetics of AMG 531 administered by S.C. route with chemotherapy.


Condition Intervention Phase
Lymphoma
 Drug: AMG 531
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Vincristine
Drug: Doxorubicin
Drug: Dexamethasone
Drug: Methotrexate
Drug: Cytarabine
Drug: Placebo
 Phase 1
Phase 2

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma
U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Highest maximum dose of AMG 531 given to treat thrombocytopenia (low platelet counts) in patients who have received chemotherapy [ Time Frame: Continual reassessment method with each 3 week cycle ] [ Designated as safety issue: Yes ]

Enrollment: 50
Study Start Date: March 2006
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: R-HyperCVAD alternating R-Ara-C/MTX + AMG531 Pre & Post Doses
R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab plus cyclophosphamide, vincristine, doxorubicin (Adriamycin) and dexamethasone (CVAD); and, R-Ara-C/MTX is Rituximab, Cytarabine and Methotrexate. AMG531 Pre & Post Doses.
 Drug: AMG 531
Arm A: AMG531 - 1, 3, or 10 mcg/kg subcutaneous injection administered on on days -5 and 5 (pre and post chemotherapy dose) beginning with Cycle 2; OR, Arm A: AMG531 - 1, 3, or 10 mcg/kg subcutaneous injection administered on on days 5 and 7 (post chemotherapy doses only) beginning with Cycle 2.
Other Name: Romiplostim
Drug: Rituximab
375 mg/m^2 by vein over 4-6 hour infusion day 1, each cycle.
Other Name: Rituxan
Drug: Cyclophosphamide
300 mg/m^2 by vein over 3 hours every 12 hours for 6 doses (days 2-4), Cycles 1,3, & 5.
Other Names:
  • Cytoxan
  • Neosar
Drug: Vincristine
1.4 mg/m^2/dose (maximum 2 mg) by vein over 15 minutes Days 5 and 12, Cycles 1,3,& 5.
Drug: Doxorubicin
50 mg/m^2/dose by vein over 15 minutes on Day 5 or by continuous infusion over 24-48 hours (days 5-6), Cycles 1,3,& 5.
Other Names:
  • AD
  • Hydroxydaunomycin hydrocholoride
Drug: Dexamethasone
40 mg/day by mouth or by vein days 2-5 and 12-15, Cycles 1,3,& 5.
Other Name: Decadron
Drug: Methotrexate
200 mg/m^2 by vein over 2 hours followed by 800 mg/m^2 over 22 hours Day 2, Cycles 2,4,& 6.
Drug: Cytarabine
3 g/m^2 by vein over 2 hours every 12 hours for 4 doses, days 3 & 4; OR,1 g/m^2 by vein over 2 hours every 12 hours for 4 doses, days 3 & 4 for patients > 60 years and for patients with serum creatinine > 1.5 mg/dL; Cycles 2,4,& 6.
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
Placebo Comparator: R-HyperCVAD alternating R-Ara-C/MTX + Placebo Pre & Post Doses
R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab plus cyclophosphamide, vincristine, doxorubicin (Adriamycin) and dexamethasone (CVAD); and, R-Ara-C/MTX is Rituximab, Cytarabine and Methotrexate. Placebo Pre & Post Doses.
 Drug: Rituximab
375 mg/m^2 by vein over 4-6 hour infusion day 1, each cycle.
Other Name: Rituxan
Drug: Cyclophosphamide
300 mg/m^2 by vein over 3 hours every 12 hours for 6 doses (days 2-4), Cycles 1,3, & 5.
Other Names:
  • Cytoxan
  • Neosar
Drug: Vincristine
1.4 mg/m^2/dose (maximum 2 mg) by vein over 15 minutes Days 5 and 12, Cycles 1,3,& 5.
Drug: Doxorubicin
50 mg/m^2/dose by vein over 15 minutes on Day 5 or by continuous infusion over 24-48 hours (days 5-6), Cycles 1,3,& 5.
Other Names:
  • AD
  • Hydroxydaunomycin hydrocholoride
Drug: Dexamethasone
40 mg/day by mouth or by vein days 2-5 and 12-15, Cycles 1,3,& 5.
Other Name: Decadron
Drug: Methotrexate
200 mg/m^2 by vein over 2 hours followed by 800 mg/m^2 over 22 hours Day 2, Cycles 2,4,& 6.
Drug: Cytarabine
3 g/m^2 by vein over 2 hours every 12 hours for 4 doses, days 3 & 4; OR,1 g/m^2 by vein over 2 hours every 12 hours for 4 doses, days 3 & 4 for patients > 60 years and for patients with serum creatinine > 1.5 mg/dL; Cycles 2,4,& 6.
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
Drug: Placebo
Arm A: Placebo - subcutaneous injection administered on days -5 and 5 (pre and post chemotherapy dose) beginning with Cycle 2; OR, Arm B: Placebo - subcutaneous injection administered on days 5 and 7 (post chemotherapy doses only) beginning with Cycle 2.
Experimental: R-HyperCVAD alternating R-Ara-C/MTX + AMG531 Post Dose Only

AMG531 - 1, 3, or 10 mcg/kg subcutaneous injection administered on on days 5 and 7 (post chemotherapy doses only) beginning with Cycle 2.

Methotrexate

 Drug: AMG 531
Arm A: AMG531 - 1, 3, or 10 mcg/kg subcutaneous injection administered on on days -5 and 5 (pre and post chemotherapy dose) beginning with Cycle 2; OR, Arm A: AMG531 - 1, 3, or 10 mcg/kg subcutaneous injection administered on on days 5 and 7 (post chemotherapy doses only) beginning with Cycle 2.
Other Name: Romiplostim
Drug: Rituximab
375 mg/m^2 by vein over 4-6 hour infusion day 1, each cycle.
Other Name: Rituxan
Drug: Cyclophosphamide
300 mg/m^2 by vein over 3 hours every 12 hours for 6 doses (days 2-4), Cycles 1,3, & 5.
Other Names:
  • Cytoxan
  • Neosar
Drug: Vincristine
1.4 mg/m^2/dose (maximum 2 mg) by vein over 15 minutes Days 5 and 12, Cycles 1,3,& 5.
Drug: Doxorubicin
50 mg/m^2/dose by vein over 15 minutes on Day 5 or by continuous infusion over 24-48 hours (days 5-6), Cycles 1,3,& 5.
Other Names:
  • AD
  • Hydroxydaunomycin hydrocholoride
Drug: Dexamethasone
40 mg/day by mouth or by vein days 2-5 and 12-15, Cycles 1,3,& 5.
Other Name: Decadron
Drug: Methotrexate
200 mg/m^2 by vein over 2 hours followed by 800 mg/m^2 over 22 hours Day 2, Cycles 2,4,& 6.
Drug: Cytarabine
3 g/m^2 by vein over 2 hours every 12 hours for 4 doses, days 3 & 4; OR,1 g/m^2 by vein over 2 hours every 12 hours for 4 doses, days 3 & 4 for patients > 60 years and for patients with serum creatinine > 1.5 mg/dL; Cycles 2,4,& 6.
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
Placebo Comparator: R-HyperCVAD alternating R-Ara-C/MTX + Placebo Post Dose Only
Methotrexate
 Drug: Rituximab
375 mg/m^2 by vein over 4-6 hour infusion day 1, each cycle.
Other Name: Rituxan
Drug: Cyclophosphamide
300 mg/m^2 by vein over 3 hours every 12 hours for 6 doses (days 2-4), Cycles 1,3, & 5.
Other Names:
  • Cytoxan
  • Neosar
Drug: Vincristine
1.4 mg/m^2/dose (maximum 2 mg) by vein over 15 minutes Days 5 and 12, Cycles 1,3,& 5.
Drug: Doxorubicin
50 mg/m^2/dose by vein over 15 minutes on Day 5 or by continuous infusion over 24-48 hours (days 5-6), Cycles 1,3,& 5.
Other Names:
  • AD
  • Hydroxydaunomycin hydrocholoride
Drug: Dexamethasone
40 mg/day by mouth or by vein days 2-5 and 12-15, Cycles 1,3,& 5.
Other Name: Decadron
Drug: Methotrexate
200 mg/m^2 by vein over 2 hours followed by 800 mg/m^2 over 22 hours Day 2, Cycles 2,4,& 6.
Drug: Cytarabine
3 g/m^2 by vein over 2 hours every 12 hours for 4 doses, days 3 & 4; OR,1 g/m^2 by vein over 2 hours every 12 hours for 4 doses, days 3 & 4 for patients > 60 years and for patients with serum creatinine > 1.5 mg/dL; Cycles 2,4,& 6.
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
Drug: Placebo
Arm A: Placebo - subcutaneous injection administered on days -5 and 5 (pre and post chemotherapy dose) beginning with Cycle 2; OR, Arm B: Placebo - subcutaneous injection administered on days 5 and 7 (post chemotherapy doses only) beginning with Cycle 2.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 </= 2 times, serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) </= 3 times the upper limit of the 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 chemotherapy.
  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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00299182

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Amgen
Investigators
Principal Investigator: Saroj Vadhan-Raj, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
The University of Texas (UT) MD Anderson Cancer Center  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00299182     History of Changes
Other Study ID Numbers: 2005-0146
Study First Received: March 3, 2006
Last Updated: March 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Cytarabine
Methotrexate
Rituximab
Dexamethasone
Doxorubicin
Vincristine
 Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on May 23, 2013