Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia

A Phase II Study of Lenalidomide (REVLIMID, NSC-703813) for Previously Untreated Non-M3, Deletion 5q Acute Myeloid Leukemia (AML) in Patients Age 60 or Older Who Decline Remission Induction Chemotherapy

This phase II trial is studying how well lenalidomide works in treating older patients with acute myeloid leukemia with abnormal chromosome 5q. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing.

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