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

NCT00299182 | Completed Phase 1 Results

• 1 other identifier: 2005-0146
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 2.To determine an optimal biologic dose (OBD) of AMG 531 in patients receiving R-HyperCVAD and R-Ara-C/MTX.
3. 3.To evaluate the effects of AMG 531 on the degree and duration of thrombocytopenia and platelet recovery following chemotherapy(chemo).

Conditions

Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Platelet (PLT) Nadir

  Blood counts were performed at least two times a week and when clinically indicated during the study and daily when PLT count is \< 50K/μL until recovery (two consecutive counts showing upward trend). The optimal biologic dose was defined as the dose of AMG 531 at which the greatest proportion of patients avoided grade 4 thrombocytopenia (Platelet nadir \< 25K/μL) in the absence of platelet transfusion in the blinded study cycle.

  Prior to start of treatment and then at least 2 times a week during treatment until end of cycle 2 (1 cycle = 21 days)

• Days Platelets Count of < 100K/μL

  The optimal biologic dose was defined as the dose of AMG 531 at which the greatest proportion of patients avoided grade 4 thrombocytopenia (Platelet nadir \< 25K/μL) in the absence of platelet transfusion in the blinded study cycle.

  Prior to start of treatment and then at least 2 times a week during treatment until end of cycle 2 (1 cycle = 21 days)

Study Arms (7)

1 mcg/ kg AMG531 Pre & Post Chemotherapy

EXPERIMENTAL

Cycle 1, Chemotherapy (R-HyperCVAD) alone. Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 1 mcg/ kg AMG 531 subcutaneously on days -5 and 5 (Arm A) R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m\^2; plus Cyclophosphamide 300 mg/m\^2, Vincristine 1.4 mg/m\^2, Doxorubicin (Adriamycin) 50 mg/m\^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m\^2; and, R-Ara-C/MTX is Rituximab 375 mg/m\^2, Cytarabine 3 g/m\^2 and Methotrexate 200 mg/m\^2.

Drug: AMG 531; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine

3 mcg/ kg AMG531 Pre & Post Chemotherapy

EXPERIMENTAL

Cycle 1, Chemotherapy (R-HyperCVAD) alone. Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 3 mcg/ kg AMG 531 subcutaneously on days -5 and 5 (Arm A) R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m\^2; plus Cyclophosphamide 300 mg/m\^2, Vincristine 1.4 mg/m\^2, Doxorubicin (Adriamycin) 50 mg/m\^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m\^2; and, R-Ara-C/MTX is Rituximab 375 mg/m\^2, Cytarabine 3 g/m\^2 and Methotrexate 200 mg/m\^2.

Drug: AMG 531; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine

10 mcg/ kg AMG531 Pre & Post Chemotherapy

EXPERIMENTAL

Cycle 1, Chemotherapy (R-HyperCVAD) alone. Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 10 mcg/ kg AMG 531 subcutaneously on days -5 and 5 (Arm A) R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m\^2; plus Cyclophosphamide 300 mg/m\^2, Vincristine 1.4 mg/m\^2, Doxorubicin (Adriamycin) 50 mg/m\^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m\^2; and, R-Ara-C/MTX is Rituximab 375 mg/m\^2, Cytarabine 3 g/m\^2 and Methotrexate 200 mg/m\^2.

Drug: AMG 531; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine

Placebo (Arm A & Arm B) with Chemotherapy

PLACEBO COMPARATOR

Placebo Pre and Post (Arm A), or Post (Arm B) Chemotherapy Cycle 1, Chemotherapy (R-HyperCVAD) alone. Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by placebo subcutaneously on days -5 and 5 (Arm A) or days 5 and 7 (Arm B) R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m\^2; plus Cyclophosphamide 300 mg/m\^2, Vincristine 1.4 mg/m\^2, Doxorubicin (Adriamycin) 50 mg/m\^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m\^2; and, R-Ara-C/MTX is Rituximab 375 mg/m\^2, Cytarabine 3 g/m\^2 and Methotrexate 200 mg/m\^2.

Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine; Drug: Placebo

1 mcg/ kg AMG531 Post Chemotherapy

EXPERIMENTAL

Cycle 1, Chemotherapy (R-HyperCVAD) alone. Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 1 mcg/ kg AMG 531 subcutaneously on days 5 and 7 (Arm B) R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m\^2; plus Cyclophosphamide 300 mg/m\^2, Vincristine 1.4 mg/m\^2, Doxorubicin (Adriamycin) 50 mg/m\^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m\^2; and, R-Ara-C/MTX is Rituximab 375 mg/m\^2, Cytarabine 3 g/m\^2 and Methotrexate 200 mg/m\^2.

Drug: AMG 531; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine

3 mcg/ kg AMG531 Post Chemotherapy

EXPERIMENTAL

Cycle 1, Chemotherapy (R-HyperCVAD) alone. Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 3 mcg/ kg AMG 531 subcutaneously on days 5 and 7 (Arm B) R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m\^2; plus Cyclophosphamide 300 mg/m\^2, Vincristine 1.4 mg/m\^2, Doxorubicin (Adriamycin) 50 mg/m\^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m\^2; and, R-Ara-C/MTX is Rituximab 375 mg/m\^2, Cytarabine 3 g/m\^2 and Methotrexate 200 mg/m\^2.

Drug: AMG 531; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine

10 mcg/ kg AMG531 Post Chemotherapy

EXPERIMENTAL

Cycle 1, Chemotherapy (R-HyperCVAD) alone. Cycle 2, Chemotherapy (R-Ara-C/MTX), followed by 10 mcg/ kg AMG 531 subcutaneously on days 5 and 7 (Arm B) R-HyperCVAD alternating with R-Ara-C/MTX where R-HyperCVAD is Rituximab 375 mg/m\^2; plus Cyclophosphamide 300 mg/m\^2, Vincristine 1.4 mg/m\^2, Doxorubicin (Adriamycin) 50 mg/m\^2, and Dexamethasone 40 mg (CVAD), Mesna 600mg/m\^2; and, R-Ara-C/MTX is Rituximab 375 mg/m\^2, Cytarabine 3 g/m\^2 and Methotrexate 200 mg/m\^2.

Drug: AMG 531; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine

Interventions

AMG 531 DRUG

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.

Also known as: Romiplostim

1 mcg/ kg AMG531 Post Chemotherapy; 1 mcg/ kg AMG531 Pre & Post Chemotherapy; 10 mcg/ kg AMG531 Post Chemotherapy; 10 mcg/ kg AMG531 Pre & Post Chemotherapy; 3 mcg/ kg AMG531 Post Chemotherapy; 3 mcg/ kg AMG531 Pre & Post Chemotherapy

Rituximab DRUG

375 mg/m\^2 by vein over 4-6 hour infusion day 1, each cycle.

Also known as: Rituxan

1 mcg/ kg AMG531 Post Chemotherapy; 1 mcg/ kg AMG531 Pre & Post Chemotherapy; 10 mcg/ kg AMG531 Post Chemotherapy; 10 mcg/ kg AMG531 Pre & Post Chemotherapy; 3 mcg/ kg AMG531 Post Chemotherapy; 3 mcg/ kg AMG531 Pre & Post Chemotherapy; Placebo (Arm A & Arm B) with Chemotherapy

Cyclophosphamide DRUG

300 mg/m\^2 by vein over 3 hours every 12 hours for 6 doses (days 2-4), Cycles 1,3, \& 5.

Also known as: Cytoxan, Neosar

1 mcg/ kg AMG531 Post Chemotherapy; 1 mcg/ kg AMG531 Pre & Post Chemotherapy; 10 mcg/ kg AMG531 Post Chemotherapy; 10 mcg/ kg AMG531 Pre & Post Chemotherapy; 3 mcg/ kg AMG531 Post Chemotherapy; 3 mcg/ kg AMG531 Pre & Post Chemotherapy; Placebo (Arm A & Arm B) with Chemotherapy

Vincristine DRUG

1.4 mg/m\^2/dose (maximum 2 mg) by vein over 15 minutes Days 5 and 12, Cycles 1,3,\& 5.

1 mcg/ kg AMG531 Post Chemotherapy; 1 mcg/ kg AMG531 Pre & Post Chemotherapy; 10 mcg/ kg AMG531 Post Chemotherapy; 10 mcg/ kg AMG531 Pre & Post Chemotherapy; 3 mcg/ kg AMG531 Post Chemotherapy; 3 mcg/ kg AMG531 Pre & Post Chemotherapy; Placebo (Arm A & Arm B) with Chemotherapy

Doxorubicin DRUG

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.

Also known as: AD, Hydroxydaunomycin hydrocholoride

1 mcg/ kg AMG531 Post Chemotherapy; 1 mcg/ kg AMG531 Pre & Post Chemotherapy; 10 mcg/ kg AMG531 Post Chemotherapy; 10 mcg/ kg AMG531 Pre & Post Chemotherapy; 3 mcg/ kg AMG531 Post Chemotherapy; 3 mcg/ kg AMG531 Pre & Post Chemotherapy; Placebo (Arm A & Arm B) with Chemotherapy

Dexamethasone DRUG

40 mg/day by mouth or by vein days 2-5 and 12-15, Cycles 1,3,\& 5.

Also known as: Decadron

1 mcg/ kg AMG531 Post Chemotherapy; 1 mcg/ kg AMG531 Pre & Post Chemotherapy; 10 mcg/ kg AMG531 Post Chemotherapy; 10 mcg/ kg AMG531 Pre & Post Chemotherapy; 3 mcg/ kg AMG531 Post Chemotherapy; 3 mcg/ kg AMG531 Pre & Post Chemotherapy; Placebo (Arm A & Arm B) with Chemotherapy

Methotrexate DRUG

200 mg/m\^2 by vein over 2 hours followed by 800 mg/m\^2 over 22 hours Day 2, Cycles 2, 4 \& 6.

1 mcg/ kg AMG531 Post Chemotherapy; 1 mcg/ kg AMG531 Pre & Post Chemotherapy; 10 mcg/ kg AMG531 Post Chemotherapy; 10 mcg/ kg AMG531 Pre & Post Chemotherapy; 3 mcg/ kg AMG531 Post Chemotherapy; 3 mcg/ kg AMG531 Pre & Post Chemotherapy; Placebo (Arm A & Arm B) with Chemotherapy

Cytarabine DRUG

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.

Also known as: Ara-C, Cytosar, DepoCyt, Cytosine arabinosine hydrochloride

1 mcg/ kg AMG531 Post Chemotherapy; 1 mcg/ kg AMG531 Pre & Post Chemotherapy; 10 mcg/ kg AMG531 Post Chemotherapy; 10 mcg/ kg AMG531 Pre & Post Chemotherapy; 3 mcg/ kg AMG531 Post Chemotherapy; 3 mcg/ kg AMG531 Pre & Post Chemotherapy; Placebo (Arm A & Arm B) with Chemotherapy

Placebo DRUG

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.

Placebo (Arm A & Arm B) with Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients age \>/= 18 years.
• Karnofsky Performance Scale \>/= 70.
• 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).
• 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.
• Institutional Review Board (IRB)-approved signed informed consent.

You may not qualify if:

• Pregnant or lactating women.
• History of Central Nervous System (CNS) involvement.
• Co-morbid medical or psychiatric illnesses that preclude treatment with intense dose chemotherapy.
• Patients with history of deep vein thrombosis (DVT) or pulmonary embolus.
• History of any platelet disorders including Idiopathic thrombocytopenic purpura (ITP), Thrombotic thrombocytopenic purpura (TTP) or bleeding disorders.
• Prior surgery or Radiation Therapy (RT) within 2 weeks of study entry.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Amgen: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center official website

MeSH Terms

Conditions

Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell

Interventions

romiplostim; Rituximab; Cyclophosphamide; Vincristine; Doxorubicin; Dexamethasone; Calcium Dobesilate; Methotrexate; Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Aminopterin; Pterins; Pteridines; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Saroj Vadhan-Raj, MD/Professor, Sarcoma Medical Oncology
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-7966

Study Officials

• Saroj Vadhan-Raj, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2006
• First Posted: March 6, 2006
• Study Start: March 1, 2006
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: September 21, 2021
• Results First Posted: September 21, 2021

Record last verified: 2021-08

Locations

US (1)