Oblimersen in Treating Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia

NCT ID: NCT00062244

Last Updated: 2013-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-05-31

Brief Summary

This phase I/II trial is studying the side effects and best dose of oblimersen and to see how well it works in treating patients with relapsed or refractory Waldenstrom's macroglobulinemia. Biological therapies such as oblimersen may interfere with the growth of the cancer cells and slow or stop the growth of Waldenstrom's macroglobulinemia.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximally tolerated dose (MTD) and recommended dosing for Genasense in patients with relapsed or refractory WM following prior chemotherapy. (Phase I) II. To determine the response rate to Genasense in patients with relapsed or refractory WM following prior chemotherapy.

III. To determine the safety of Genasense in patients with relapsed or refractory WM following prior chemotherapy.

IV. To describe possible clinical benefit from Genasense treatment of relapsed or refractory WM including duration of response, survival, erythropoietin use, improvement in hemoglobin > 11 g/dl, and Improvement in platelet count > 100,000/mm^3.

OUTLINE: This is a multicenter, dose-escalation study.

Phase I: Patients receive oblimersen IV continuously on days 1-7. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 1-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive treatment as in phase I at the MTD of oblimersen. Patients are followed every 3 months for 2 years.

Conditions

Waldenström Macroglobulinemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Phase I: Patients receive oblimersen IV continuously on days 1-7. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 1-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive treatment as in phase I at the MTD of oblimersen. Patients are followed every 3 months for 2 years.

Group Type: EXPERIMENTAL

oblimersen sodium

Intervention Type: BIOLOGICAL

Given IV

Interventions

oblimersen sodium

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

augmerosen; G3139; G3139 bcl-2 antisense oligodeoxynucleotide; Genasense

Eligibility Criteria

Inclusion Criteria

• Diagnosis of Waldenstrom's macroglobulinemia (WM) confirmed by both of the following:

• Bone marrow lymphoplasmacytosis with greater than 10% lymphoplasmacytic cells or aggregates, sheets, lymphocytes, plasma cells, or lymphoplasmacytic cells on bone marrow biopsy
• Measurable disease, defined by quantitative IgM monoclonal protein greater than 1,000 mg/dL
• Symptomatic relapsed or refractory disease requiring therapy, defined by at least 1 of the following:

• Impaired bone marrow function due to disease infiltration as demonstrated by any of the following:

• Hemoglobin less than 11 g/dL
• Requires epoetin alfa therapy to maintain hemoglobin of at least 11 g/dL
• Platelet count less than 100,000/mm^3
• Symptomatic bulky lymphadenopathy
• Symptoms attributable to hyperviscosity (e.g., nose bleeding, gingival bleeding, or retinal hemorrhage) or serum viscosity level relative to water greater than 4
• Received at least 1 prior chemotherapy regimen which included chlorambucil, cyclophosphamide, fludarabine, cladribine, or pentostatin
• No secondary leukemia or history of antecedent hematologic disorder (e.g., myelodysplasia) prior to initial onset of WM
• Performance status - ECOG 0-2
• Not specified
• See Disease Characteristics
• Absolute neutrophil count at least 1,000/mm^3*
• Platelet count at least 50,000/mm^3*
• No bleeding disorder
• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST less than 1.5 times ULN
• Albumin at least 2.5 g/dL
• PT no greater than 1.5 times ULN
• INR no greater than 1.3
• PTT no greater than 1.5 times ULN
• No history of chronic hepatitis or cirrhosis
• Creatinine no greater than 2 times ULN
• No uncontrolled congestive heart failure
• No active symptoms of coronary artery disease, including the following:

• Uncontrolled arrhythmias
• Recurrent chest pain despite prophylactic medication
• No New York Heart Association class III or IV heart disease
• No grade 2 or greater cardiovascular signs and symptoms within the past 4 weeks
• HIV negative
• Direct Coombs' test negative
• No autoimmune thrombocytopenia
• No uncontrolled serious infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Adequate venous access for 7-day continuous infusion of study drug
• Intellectual, emotional, and physical ability to maintain an ambulatory infusion pump
• No other cancer except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other cancer from which the patient has been disease-free for at least 5 years
• No known hypersensitivity to phosphorothioate-containing oligonucleotides
• No uncontrolled seizure disorder
• More than 21 days since prior immunotherapy for WM
• More than 21 days since prior cytokine, biologic, or vaccine therapy for WM
• More than 8 weeks since prior plasmapheresis or plasma exchange
• No prior allogeneic stem cell transplantation
• No concurrent plasmapheresis or plasma exchange
• See Disease Characteristics
• No concurrent corticosteroid therapy
• More than 21 days since prior radiotherapy for WM
• More than 21 days since prior major surgery for WM
• No prior organ allograft
• Recovered from all prior therapy
• More than 21 days since other prior therapy for WM
• No other concurrent investigational therapy
• No concurrent immunosuppressive drugs
• No concurrent therapeutic anticoagulation therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Morie Gertz

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Howard University Hospital

Washington D.C., District of Columbia, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

Johns Hopkins University

Baltimore, Maryland, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

MC0285

Identifier Type: -

Identifier Source: secondary_id

MAYO-MC0285

Identifier Type: -

Identifier Source: secondary_id

NCI-5826

Identifier Type: -

Identifier Source: secondary_id

CDR0000304634

Identifier Type: -

Identifier Source: secondary_id

N01CM17104

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01437

Identifier Type: -

Identifier Source: org_study_id