Bevacizumab With or Without Thalidomide in Treating Patients With Relapsed or Refractory Multiple Myeloma

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00022607
First received: August 10, 2001
Last updated: June 20, 2013
Last verified: October 2004
  Purpose

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Thalidomide may stop the growth of cancer cells by stopping blood flow to the tumor. It is not yet known whether bevacizumab works better with or without thalidomide for multiple myeloma.

PURPOSE: This randomized phase II trial is to see if bevacizumab works better with or without thalidomide in treating patients who have relapsed or refractory multiple myeloma.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Biological: bevacizumab
Drug: thalidomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Phase II Randomized Trial of Bevacizumab Versus Bevacizumab and Thalidomide for Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: January 2002
Study Completion Date: May 2006
Detailed Description:

OBJECTIVES:

  • Compare the response rate and time to progression in patients with relapsed or refractory multiple myeloma treated with bevacizumab with or without thalidomide.
  • Compare the toxicity of these regimens in these patients.
  • Compare the effects of these regimens on histological and molecular biomarkers of angiogenesis, tumor invasion, and cell death in these patients.
  • Correlate plasma and urine vascular endothelial growth factor and basic fibroblast growth factor levels and other potential markers of angiogenesis and myeloma cell proliferation with outcome in patients treated with these regimens.
  • Determine the pharmacokinetics of thalidomide in these patients.
  • Compare the effects of these regimens on the psychological/physical well being of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior treatment with thalidomide (yes vs no).

Patients who have received no prior treatment with thalidomide are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, 29, and 43. Patients also receive oral thalidomide once daily.
  • Arm II: Patients receive bevacizumab as in arm I. Patients who have received prior treatment with thalidomide receive bevacizumab as in arm I.

Courses repeat every 56 days in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 3 months and then every 3-4 months for 3 years.

PROJECTED ACCRUAL: A total of 55-103 patients (16-32 who have received prior thalidomide, 16-32 in arm I, and 23-39 in arm II) will be accrued for this study within 2.5 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed progressing multiple myeloma

    • Stages I, II, or III
    • More than 25% increase in urine or plasma paraprotein levels
    • More than 5% malignant plasma cell involvement in bone marrow
  • Smoldering myeloma is eligible provided there is evidence of progressive disease requiring therapy

    • At least 25% increase in M protein levels or Bence Jones excretion
    • Hemoglobin no greater than 10.5 g/dL
    • Frequent infections
    • Hypercalcemia
    • Rise in serum creatinine above normal on 2 separate occasions
  • Nonsecretory multiple myeloma that is bidimensionally measurable by MRI or CT scan is eligible provided the disease site is new or has shown an increase in M protein levels or Bence Jones excretion is greater than 30% from baseline
  • No prior or concurrent CNS involvement with primary or metastatic tumor
  • No nonquantifiable monoclonal proteins or IgM peaks unless there is evidence of bidimensionally measurable disease by MRI or CT scan
  • No history of hemorrhagic tumor or hemorrhagic metastasis

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Karnofsky 70-100%

Life expectancy:

  • At least 3 months

Hematopoietic:

  • See Disease Characteristics
  • Absolute neutrophil count ≥1,000/mm^3
  • Platelet count ≥ 50,000/mm^3
  • No hemorrhagic illness within the past 3 weeks

Hepatic:

  • Bilirubin ≤ 1.5 mg/dL
  • SGOT/SGPT≤ 2.5 times upper limit of normal (ULN)
  • INR ≤ 1.5
  • aPTT < 1.5 times ULN

Renal:

  • See Disease Characteristics
  • Creatinine ≤ 2 mg/dL
  • Creatinine clearance ≥ 40 mL/min
  • Calcium ≤ 12 mg/dL
  • No nephrotic syndrome

Cardiovascular:

  • No active coronary artery disease
  • No New York Heart Association class II-IV congestive heart failure
  • No grade II or greater peripheral vascular disease (i.e, ischemic rest pain, non-healing ulcer, or tissue loss)
  • No uncontrolled hypertension
  • No history of deep venous thrombosis
  • No vascular illness within the past 3 weeks
  • No arterial thromboembolic event within the past 6 months, including any of the following:

    • Transient ischemic attack
    • Cerebrovascular accident
    • Unstable angina
    • Myocardial infarction

Pulmonary:

  • No history of pulmonary embolus

Other:

  • No other prior malignancy unless the patient has been in complete remission for at least 2 years
  • No peripheral neuropathy or CNS abnormalities ≥ grade 2

    • Patients with prior exposure to thalidomide and assigned to arm I may have grade 2 peripheral or CNS abnormalities
  • No seizure disorder
  • No serious non-healing wound, ulcer, or bone fracture
  • No trauma within the past 3 weeks
  • No significant inflammatory illness within the past 3 weeks
  • No known hypersensitivity to Chinese hamster ovary cell products
  • No known hypersensitivity to other recombinant human or humanized antibodies and/or positive human antimurine antibodies/human antichimeric antibodies
  • No other significant medical, psychological, or social problem that would preclude study participation
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception for at least 2 weeks before and during study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Chemotherapy
  • Prior nonmyeloablative transplantation allowed provided the following are true:

    • Patient is not receiving concurrent immunosuppressive therapy
    • Patient has no signs of graft-versus-host disease
  • Concurrent epoetin alfa allowed if started at least 4 weeks prior to study entry

Chemotherapy:

  • No more than 5 prior chemotherapy regimens

    • Thalidomide, steroids, and interferon are not considered part of prior regimens
    • Mobilization with chemotherapy followed by either single or tandem autologous transplantation is counted as 1 prior regimen
    • Mobilization with chemotherapy followed by autologous and subsequent nonmyeloablative HLA-matched sibling allogeneic transplantation is counted as 1 prior regimen
  • At least 3 weeks since prior chemotherapy
  • No concurrent chemotherapy

Endocrine therapy:

  • See Chemotherapy
  • At least 2 weeks since prior steroids
  • No concurrent steroids

Radiotherapy:

  • At least 3 weeks since prior radiotherapy
  • No concurrent radiotherapy

Surgery:

  • At least 3 weeks since prior surgery, including biopsy of a visceral organ

Other:

  • At least 10 days since prior anticoagulants, including aspirin
  • At least 2 days since prior nonsteroidal anti-inflammatory agents
  • Concurrent bisphosphonates allowed
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00022607

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089
University of California Davis Cancer Center
Sacramento, California, United States, 95817
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
Sponsors and Collaborators
California Cancer Consortium
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00022607     History of Changes
Other Study ID Numbers: CDR0000068834, CCC-PHII-30, CHNMC-PHII-30, CHNMC-IRB-01006, NCI-2712
Study First Received: August 10, 2001
Last Updated: June 20, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Thalidomide
Bevacizumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 28, 2014