Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Myelomonocytic Leukemia (M4), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Secondary Acute Myeloid Leukemia, Untreated Adult Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: lenalidomide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (lenalidomide)<br>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. | Drug: lenalidomide<br>* Given orally<br>* Other names: Revlimid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response | Morphologic complete remission (CR): ANC >=1,000/mcl, platelet count >=100,000/mcl, <5% bone marrow blasts, no Auer rods, no evidence of extramedullary disease. Morphologic complete remission with incomplete blood count recovery (CRi): Same as CR but ANC may be <1,000/mcl and/or platelet count <100,000/mcl. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Only adverse events that are possibly, probably or definitely related to study drug are reported. | Up to 5 years | 
| Cytogenetic Abnormalities | Number of baseline cytogenetic abnormalities by responders (CR, CRi, and PR) and nonresponders. | Up to 5 years | 
| Total Response | Morphologic complete remission (CR): ANC >=1,000/mcl, platelet count >=100,000/mcl, <5% bone marrow blasts, no Auer rods, no evidence of extramedullary disease. Morphologic complete remission with incomplete blood count recovery (CRi): Same as CR but ANC may be <1,000/mcl and/or platelet count <100,000/mcl. Partial remission (PR): ANC >1,000/mcl, platelet count >100,000/mcl, and at least 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts <5% with persistent Auer rods. | Up to 5 years |