Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. Test whether the complete response rate among older patients with previously untreated acute myeloid leukemia (AML) with the del (5q) cytogenetic abnormality treated with lenalidomide is sufficiently high to warrant a phase III investigation.

II. Estimate the frequency and severity of toxicities of this drug in these patients.

III. Correlate, in a preliminary manner, additional cytogenetic abnormalities with response to lenalidomide.

IV. Estimate the total (complete and partial) response rate and the cytogenetic response rate in these patients.

OUTLINE:

INDUCTION THERAPY: Patients receive oral lenalidomide once daily on days 1-14, 1-21, or 1-28 (course 1). Patients undergo bone marrow biopsy on day 28 or 35 to assess treatment efficacy. Patients with stable or improving disease (i.e., a decrease in blast percentage) without progressive disease proceed to maintenance therapy.

MAINTENANCE THERAPY: Beginning within 42 days after completion of induction therapy, patients receive oral lenalidomide once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years.

Inclusion criteria

• Morphologically confirmed diagnosis of acute myeloid leukemia (AML) by bone marrow aspiration and biopsy within the past 14 days

• Diagnostic biopsy within the past 28 days with marrow blast percentage ≥ 70% allowed provided no potentially antileukemic therapy was received after biopsy
• Cytogenetic evidence of del (5q) abnormality by conventional karyotyping or fluorescence in situ hybridization (FISH)
• Previously untreated disease

• Must have declined standard AML cytotoxic chemotherapy regimens
• WBC ≤ 30,000/mm³
• History of prior myelodysplastic syndromes (MDS) allowed
• No acute promyelocytic leukemia (FAB M3)
• No blastic transformation of chronic myelogenous leukemia
• Zubrod performance status 0-2
• Bilirubin ≤ 2.5 times upper limit of normal (ULN) (unless elevation is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome or hemolysis, but not to liver dysfunction)
• AST and ALT ≤ 3.5 times ULN
• Creatinine ≤ 1.5 times ULN
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 forms of effective contraception at least 4 weeks prior to, during, and for 4 weeks after completion of study treatment
• No known allergy to thalidomide
• Concurrent enrollment on SWOG-S9910 allowed (for SWOG patients)
• No prior systemic chemotherapy for acute leukemia except hydroxyurea

• Single-dose intrathecal chemotherapy allowed before or concurrently with induction chemotherapy
• No prior AML induction-type chemotherapy or high-dose chemotherapy with hematopoietic stem cell support
• Prior hematopoietic growth factors, thalidomide, arsenic trioxide, signal-transduction inhibitors, azacitidine, and low-dose cytarabine (i.e., < 100 mg/m²/day) for treatment of MDS allowed
• At least 30 days since prior therapy for MDS (excluding growth factors)
• No prior lenalidomide for MDS
• At least 6 months since prior chemotherapy or radiotherapy for another malignancy
• No concurrent therapy for another malignancy
• Concurrent hormonal therapy allowed