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

Sponsor

California Cancer Consortium (Other)

Overall Status

Completed

CT.gov ID

NCT00022607

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

51.9

Duration (Months)

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: bevacizumab Drug: thalidomide	Phase 2

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

Phase II Randomized Trial of Bevacizumab Versus Bevacizumab and Thalidomide for Relapsed/Refractory Multiple Myeloma

Study Start Date :

Jan 1, 2002

Actual Study Completion Date :

May 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
2	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089
3	University of California Davis Cancer Center	Sacramento	California	United States	95817
4	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470