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

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Phase 1

Conditions

Waldenström Macroglobulinemia

Treatments

Biological: oblimersen sodium

Study type

Interventional

Funder types

NIH

Identifiers

NCT00062244

MC0285

CDR0000304634

NCI-5826

MAYO-MC0285

N01CM17104 (U.S. NIH Grant/Contract)

NCI-2012-01437

Details and patient eligibility

About

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.

Full 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.

Enrollment

58 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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