3-AP Followed By Fludarabine In Treating Patients With Relapsed or Refractory Acute or Chronic Leukemia or High-Risk Myelodysplastic Syndrome

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: National Cancer Institute (NCI)
• Treatments: Fludarabine; Fludarabine phosphate; Vidarabine

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