Chemotherapy in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia
Recruitment status was Active, not recruiting
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known which regimen of chemotherapy is more effective for chronic lymphocytic leukemia.
PURPOSE: This randomized phase III trial is studying chlorambucil to see how well it works compared to fludarabine and cyclophosphamide or fludarabine alone in treating patients with newly diagnosed chronic lymphocytic leukemia.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia |
Drug: chlorambucil Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: fludarabine phosphate Drug: prednisolone Drug: vincristine sulfate |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Primary Purpose: Treatment |
| Official Title: | Chronic Lymphocytic Leukemia Trial 4: A Randomized Comparison of Chlorambucil, Fludarabine and Fludarabine Plus Cyclophosphamide |
| Study Start Date: | October 1999 |
OBJECTIVES:
- Compare the survival rate of patients with newly diagnosed chronic lymphocytic leukemia treated with chlorambucil alone vs fludarabine with or without cyclophosphamide.
- Compare the response rate and duration of remission in patients treated with these regimens.
- Compare the toxic effects of these regimens in these patients.
- Compare the quality of life of patients treated with these regimens.
- Determine the impact of the drug response information provided by the DiSC assay on response rate and survival in relapsed or nonresponding patients.
- Assess the prognostic value of five genetic markers: trisomy 12 and deletions at 11q23, 13q14, p53, and 6q21 in patients treated with these regimens.
OUTLINE: This is a randomized study. Patients enter one of three treatment arms in the first randomization. Depending on response, some patients may also participate in a second randomization to one of two treatment arms.
First randomization:
- Arm I: Patients receive oral chlorambucil daily for 7 days. Treatment repeats every 4 weeks until maximum response or up to 1 year.
- Arm II: Patients receive fludarabine IV or orally daily for 5 days. Treatment repeats every 4 weeks for 3-8 courses.
- Arm III: Patients receive cyclophosphamide IV and fludarabine IV for 3 days or orally daily for 5 days. Treatment repeats every 4 weeks for 3-8 courses.
Patients who relapse after being in remission for at least 1 year may repeat the initial therapy or may participate in a second randomization. Patients who experience progressive disease or relapse within 1 year after treatment proceed to a second randomization.
Second randomization:
- Arm I: Treatment is guided by the results of the DiSC assay. Treatment may be one of the first-line treatments with fludarabine or standard CHOP chemotherapy repeated every 4 weeks (cyclophosphamide IV, doxorubicin IV, vincristine IV, and oral prednisolone on days 1-5) or any other therapy guided by the results of the DiSC assay.
- Arm II: Treatment is physician's choice, which may include any of the options in arm I.
Quality of life is assessed prior to initial therapy; at 3, 6, and 12 months; and then annually thereafter.
Patients are followed annually for survival.
PROJECTED ACCRUAL: A total of 750 patients will be accrued for this study within 6-7 years.
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Diagnosis of B-cell chronic lymphocytic leukemia (CLL) requiring therapy and meeting the following criteria:
- Previously untreated disease
- Peripheral blood morphology, excluding other leukemia and low-grade lymphoma in leukemic phase
- Cell markers: CD5+, CD23+, SmIg (weak), CD79b-, FMC7-
- Persistent lymphocytosis (greater than 10,000/mm^3)
- At least 40% bone marrow infiltration
Stage 0 or I progressive disease indicated by at least one of the following:
- Persistent rise in lymphocyte count with doubling time less than 12 months
- Downward trend in hemoglobin and/or platelet count
- At least 50% increase in size of liver and/or spleen and/or lymph nodes
- Appearance of lymphadenopathy, hepatomegaly, or splenomegaly
Constitutional symptoms caused by disease
- Pyrexia
- Night sweats
- Weight loss OR
- Stage II or III
PATIENT CHARACTERISTICS:
Age:
- Not specified
Performance status:
- Not specified
Life expectancy:
- Not specified
Hematopoietic:
- See Disease Characteristics
Hepatic:
- Bilirubin no greater than 2 times upper limit of normal (ULN)*
- SGOT/SGPT no greater than 2 times ULN* NOTE: * Unless due to CLL
Renal:
- Creatinine clearance at least 30 mL/min
Other:
- No other cancer or life-threatening disease
- Not pregnant
- Fertile patients must use effective contraception during and for 6 months after study therapy
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- Not specified
Endocrine therapy
- No concurrent corticosteroids (e.g., dexamethasone) as antiemetics
Radiotherapy
- Not specified
Surgery
- Not specified
Contacts and Locations
Show 86 Study Locations| Study Chair: | Daniel Catovsky, MD | Royal Marsden NHS Foundation Trust |
More Information
Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| ClinicalTrials.gov Identifier: | NCT00004218 History of Changes |
| Obsolete Identifiers: | NCT00222599 |
| Other Study ID Numbers: | CDR0000067454, LRF-CLL4, LRG-MRC-LEUK-CLL4, EU-99030, MRC-LEUK-CLL4, EUDRACT-58585610, ISRCTN58585610 |
| Study First Received: | January 28, 2000 |
| Last Updated: | February 15, 2012 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Cancer Institute (NCI):
|
stage I chronic lymphocytic leukemia stage II chronic lymphocytic leukemia stage III chronic lymphocytic leukemia B-cell chronic lymphocytic leukemia stage 0 chronic lymphocytic leukemia |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Leukemia, B-Cell Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Chlorambucil Cyclophosphamide Fludarabine Fludarabine monophosphate Doxorubicin |
Prednisolone Methylprednisolone Hemisuccinate Vincristine Methylprednisolone acetate Prednisolone acetate Methylprednisolone Prednisolone hemisuccinate Prednisolone phosphate Vidarabine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 21, 2013