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

Primary Purpose

Leukemia

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
filgrastim
oblimersen sodium
cyclophosphamide
fludarabine phosphate
Sponsored by
Genta Incorporated
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring refractory chronic lymphocytic leukemia, B-cell chronic lymphocytic leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Genta Incorporated

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
September 13, 2001
Last Updated
January 3, 2014
Sponsor
Genta Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT00024440
Brief Title
Fludarabine and Cyclophosphamide With or Without Oblimersen in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Official Title
Randomized Study Of Fludarabine And Cyclophosphamide With Or Without Genasense (Bcl-2 Antisense Oligonucleotide) In Subjects With Relapsed Or Refractory Chronic Lymphocytic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
October 2003
Overall Recruitment Status
Completed
Study Start Date
July 2001 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
February 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Genta Incorporated

4. Oversight

5. Study Description

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.
Detailed Description
OBJECTIVES: Compare the complete response and nodular partial response of patients with relapsed or refractory chronic lymphocytic leukemia treated with fludarabine and cyclophosphamide with or without oblimersen. Compare the overall response rate, response duration, survival, and time to progression in patients treated with these regimens. Compare the clinical benefit and safety of these regimens in these patients. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to disease response to prior fludarabine-containing therapy (responsive vs refractory), number of prior regimens (1-2 vs 3 or more), and duration of response to last prior therapy (more than 6 months vs 6 months or fewer). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oblimersen IV continuously on days 1-7 via an infusion pump (ending on day 8) and fludarabine IV over 20-30 minutes and cyclophosphamide IV over 30-60 minutes on days 5-7. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 11 and continuing until blood counts recover. Arm II: Patients receive fludarabine IV over 20-30 minutes followed by cyclophosphamide IV over 30-60 minutes on days 1-3. Patients also receive G-CSF SC beginning on day 7 and continuing until blood counts recover. Treatment in both arms continues every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed at 1 month and then every 2 months for 2 years. PROJECTED ACCRUAL: A total of 200 patients (100 per arm) will be accrued for this study within 1 year.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
refractory chronic lymphocytic leukemia, B-cell chronic lymphocytic leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Masking
None (Open Label)
Allocation
Randomized

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Biological
Intervention Name(s)
oblimersen sodium
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stanley R. Frankel, MD
Organizational Affiliation
Genta Incorporated
Official's Role
Study Chair
Facility Information:
Facility Name
Genta Incorporated
City
Berkeley Heights
State/Province
New Jersey
ZIP/Postal Code
07922
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19738118
Citation
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.
Results Reference
result
PubMed Identifier
17296974
Citation
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. Erratum In: J Clin Oncol. 2008 Feb 10;26(5):820.
Results Reference
result

Learn more about this trial

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

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