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


Phase 2
18 Years
N/A
Not Enrolling
Both
Multiple Myeloma and Plasma Cell Neoplasm

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Authority:

United States: Federal Government

Study ID:

CDR0000068834

NCT ID:

NCT00022607

Start Date:

January 2002

Completion Date:

May 2006

Related Keywords:

  • Multiple Myeloma and Plasma Cell Neoplasm
  • refractory multiple myeloma
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • Neoplasms
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma

Name

Location

University of Chicago Cancer Research CenterChicago, Illinois  60637
USC/Norris Comprehensive Cancer Center and HospitalLos Angeles, California  90033-0804
University of California Davis Cancer CenterSacramento, California  95817
City of Hope Comprehensive Cancer CenterDuarte, California  91010