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

NCT00024440 | Completed Phase 3

• 3 other identifiers: CDR0000068932GENTA-GL303UCLA-0104008
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Leukemia

Keywords

refractory chronic lymphocytic leukemia; B-cell chronic lymphocytic leukemia

Interventions

filgrastim BIOLOGICAL

oblimersen sodium BIOLOGICAL

cyclophosphamide DRUG

fludarabine phosphate DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Genta Incorporated: lead

Study Sites (1)

Genta Incorporated

Berkeley Heights, New Jersey, 07922, United States

Location

Related Publications (2)

• O'Brien S, Moore JO, Boyd TE, Larratt LM, Skotnicki AB, Koziner B, Chanan-Khan AA, Seymour JF, Gribben J, Itri LM, Rai KR. 5-year survival in patients with relapsed or refractory chronic lymphocytic leukemia in a randomized, phase III trial of fludarabine plus cyclophosphamide with or without oblimersen. J Clin Oncol. 2009 Nov 1;27(31):5208-12. doi: 10.1200/JCO.2009.22.5748. Epub 2009 Sep 8.

  PMID: 19738118 RESULT

• O'Brien S, Moore JO, Boyd TE, Larratt LM, Skotnicki A, Koziner B, Chanan-Khan AA, Seymour JF, Bociek RG, Pavletic S, Rai KR. Randomized phase III trial of fludarabine plus cyclophosphamide with or without oblimersen sodium (Bcl-2 antisense) in patients with relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2007 Mar 20;25(9):1114-20. doi: 10.1200/JCO.2006.07.1191. Epub 2007 Feb 12.

  PMID: 17296974 RESULT

MeSH Terms

Conditions

Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Filgrastim; oblimersen; Cyclophosphamide; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Stanley R. Frankel, MD

  Genta Incorporated

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 13, 2001
• First Posted: January 27, 2003
• Study Start: July 1, 2001
• Study Completion: February 1, 2007
• Last Updated: January 6, 2014

Record last verified: 2003-10

Locations

US (1)