Chronic Lymphocytic Leukemia Clinical Trial
3-AP Followed By Fludarabine In Treating Patients With Relapsed or Refractory Acute or Chronic Leukemia or High-Risk Myelodysplastic Syndrome
Summary
RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. 3-AP may help fludarabine kill more cancer cells by making them more sensitive to the drug.
PURPOSE: This phase I trial is studying the side effects and best dose of fludarabine when given together with 3-AP in treating patients with relapsed or refractory acute leukemia, chronic leukemia, or high-risk myelodysplastic syndrome.
Full Description
OBJECTIVES:
Determine the feasibility and tolerability of 3-AP (Triapine^® ) followed by fludarabine in patients with relapsed or refractory acute or chronic leukemia or high-risk myelodysplastic syndromes.
Determine the toxic effects of this regimen in these patients.
Determine the maximum tolerated dose of this regimen in these patients.
OUTLINE: This is a multicenter, dose-escalation study of fludarabine. Patients are stratified according to disease (acute leukemias and myelodysplastic syndromes [MDS] vs chronic lymphocytic leukemia and prolymphocytic leukemia). Patients are assigned to 1 of 2 treatment groups.
Group 1 (chronic lymphocytic leukemia or prolymphocytic leukemia): Patients receive 3-AP (Triapine^®) IV over 4 hours and fludarabine IV over 30 minutes on days 1-5.
Cohorts of 3-6 patients receive escalating doses of fludarabine 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. Once the MTD is determined, 10 additional patients are treated at that dose level.
Group 2 (acute leukemias or MDS): Patients receive 3-AP IV continuously over 24 hours on day 1. Beginning within 4 hours after completion of 3-AP, patients receive fludarabine IV over 30 minutes on days 2-6.
In both groups, treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: A total of 3-34 patients will be accrued for this study.
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed diagnosis of 1 of the following:
High-risk myelodysplastic syndromes (MDS), including refractory anemia with excess blasts and chronic myelomonocytic leukemia
International Prognostic Scoring System (IPSS) score at least 1.5 based on the following:
More than 10% marrow blasts
Cytopenias in at least 2 lineages
Adverse cytogenetics
Acute myeloid leukemia (AML)
All subtypes, including MDS/AML and treatment-related (secondary) AML
Acute lymphoblastic leukemia
Acute progranulocytic leukemia
Ineligible for arsenic therapy
Chronic myelogenous leukemia
Accelerated phase or blastic crisis
Chronic lymphocytic leukemia
Prolymphocytic leukemia
Received or ineligible for established curative regimens, including stem cell transplantation
Acute and chronic leukemias must be relapsed and/or refractory with progressive disease since last therapy
PATIENT CHARACTERISTICS:
Age
18 and over
Performance status
ECOG 0-2
Life expectancy
Not specified
Hematopoietic
No history of hemolytic anemia grade 2 or greater
No known glucose-6-phosphate dehydrogenase (G6PD) deficiency
G6PD screening required for high-risk groups (i.e., patients of African, Asian, or Mediterranean origin/ancestry)
Hepatic
SGOT and SGPT no greater than 2.5 times normal
Bilirubin no greater than 2 mg/dL
No chronic hepatitis
Renal
Creatinine normal OR
Creatinine clearance at least 60 mL/min
Cardiovascular
No active heart disease
No myocardial infarction within the past 3 months
No severe coronary artery disease
No arrhythmias (other than atrial flutter or fibrillation) requiring medication
No uncontrolled congestive heart failure
Pulmonary
No dyspnea at rest or with minimal exertion
No severe pulmonary disease requiring supplemental oxygen
Other
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No neuropathy grade 2 or greater
No active uncontrolled infection
Infections under active treatment and controlled by antibiotics are allowed
No other life-threatening illness
No psychiatric illness that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
See Disease Characteristics
At least 1 week since prior hematopoietic growth factor (e.g., epoetin alfa, filgrastim [G-CSF], sargramostim [GM-CSF], interleukin-3, and interleukin-11)
No concurrent immunotherapy
Chemotherapy
Recovered from prior chemotherapy (no greater than grade 1 chronic toxic effects)
At least 72 hours since prior hydroxyurea
At least 3 weeks since prior myelosuppressive cytotoxic agents (6 weeks for mitomycin or nitrosoureas)
No more than 12 prior courses of fludarabine
No more than 3 prior cytotoxic chemotherapy regimens
No other concurrent chemotherapy
Endocrine therapy
Not specified
Radiotherapy
At least 2 weeks since prior radiotherapy
No concurrent radiotherapy
Surgery
Not specified
Other
At least 1 week since prior non-myelosuppressive treatment
No more than 4 prior induction regimens
No other concurrent therapy
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There are 4 Locations for this study
Atlanta Georgia, 30342, United States
Baltimore Maryland, 21201, United States
Baltimore Maryland, 21231, United States
Houston Texas, 77030, United States
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