Fludarabine and Cyclophosphamide With or Without Oblimersen in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

• Status: Completed
• Trial end date: 2007-02-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may help fludarabine and cyclophosphamide kill more cancer cells by making them more sensitive to the drugs. It is not yet known if fludarabine and cyclophosphamide are more effective with or without oblimersen.

PURPOSE: Randomized phase III trial to compare the effectiveness of fludarabine and cyclophosphamide with or without oblimersen in treating patients who have relapsed or refractory chronic lymphocytic leukemia.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Genta Incorporated
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Oblimersen; Vidarabine

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of relapsed or refractory chronic lymphocytic leukemia (CLL) requiring therapy

• Primary resistance, defined as disease progression without response during at least 2 courses of myelosuppressive therapy OR

• Relapsed disease, defined as a response (remission or plateau) followed by relapse on or off prior therapy

• At least 1 prior regimen must have contained fludarabine

• Intermediate or high-risk CLL

• Intermediate-risk disease must satisfy at least 1 of the following criteria for active disease:

• Massive or progressive splenomegaly and/or lymphadenopathy

• Spleen tip greater than 6 cm below costal margin

• More than 10% weight loss within the past 6 months

• Grade 2 or 3 fatigue

• Fevers greater than 100.5 degrees F or night sweats for more than 2 weeks without evidence of infection

• Progressive lymphocytosis with an increase of more than 50% over a 2-month period or an anticipated doubling time of less than 6 months

• Worsening anemia or thrombocytopenia

• Measurable disease with all of the following:

• Absolute lymphocytosis greater than 5,000/mm^3

• Lymphocytosis of small to moderate-size lymphocytes with less than 55% prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically determined by manual differential

• Bone marrow aspirate smear with at least 30% nucleated cells that are lymphoid or a bone marrow core biopsy showing lymphoid infiltrates compatible with CLL

• Normocellular or hypercellular bone marrow

• Lymphocyte immunophenotype that shows a predominant B-cell monoclonal population

• No Rai stage 0 CLL or stable CLL not requiring therapy

• No secondary leukemia or history of antecedent hematologic disorder prior to initial onset of CLL (e.g., myelodysplasia)

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

• Platelet count at least 50,000/mm^3 (hematopoietic growth factor or transfusion independent)

• Negative Coombs' test

• No bleeding or coagulation disorder

• No history of hemolytic anemia, including autoimmune hemolytic anemia

• No history of autoimmune thrombocytopenia

Hepatic:

• Albumin at least 3.0 g/dL

• Bilirubin no greater than 2 mg/dL

• AST no greater than 1.5 times upper limit of normal (ULN) (5 times ULN if due to CLL)

• PT no greater than 1.5 times ULN OR

• INR no greater than 1.3

• PTT no greater than 1.5 times ULN

• No chronic hepatitis or cirrhosis

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No uncontrolled congestive heart failure

• No active symptoms of coronary artery disease (i.e., uncontrolled arrhythmia or recurrent chest pain despite prophylactic medication)

• No New York Heart Association class III or IV disease

• No cardiovascular signs or symptoms grade 2 or greater

Other:

• Able to maintain an ambulatory infusion pump

• HIV negative

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

• No known hypersensitivity to phosphorothioate-containing oligonucleotides, fludarabine, or cyclophosphamide

• No concurrent medical disease that would preclude study participation

• No uncontrolled seizure disorder

• No unresolved serious infection

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior autologous or allogeneic stem cell transplantation

• At least 3 weeks since prior immunologic therapy, cytokine therapy, vaccine therapy, or other biologic therapy for CLL and recovered

• No concurrent interleukin-11

Chemotherapy:

• See Disease Characteristics

• At least 3 weeks since prior chemotherapy and recovered

Endocrine therapy:

• No concurrent corticosteroid therapy

Radiotherapy:

• At least 3 weeks since prior radiotherapy for CLL and recovered

Surgery:

• No prior organ allograft

• At least 3 weeks since prior major surgery for CLL and recovered

Other:

• At least 3 weeks since other prior therapy for CLL and recovered

• No other concurrent investigational therapy

• No concurrent therapeutic anticoagulation

• No concurrent immunosuppressive drugs