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.

Study Overview

• Status: Completed
• Conditions: 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; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia
• Intervention / Treatment: Drug: lenalidomide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Redding, California, United States, 96001
      • Shasta Regional Medical Center
    • Roseville, California, United States, 95661
      • Sutter Roseville Medical Center
    • Sacramento, California, United States, 95816
      • Sutter General Hospital
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Center of Decatur
    • Springfield, Illinois, United States, 62781-0001
      • Memorial Medical Center
  • Kansas
    • Salina, Kansas, United States, 67401
      • Salina Regional Health Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Montana
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • Montana Cancer Consortium CCOP
    • Billings, Montana, United States, 59102
      • Hematology-Oncology Centers of the Northern Rockies PC
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic
    • Billings, Montana, United States, 59107
      • Deaconess Medical Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Butte, Montana, United States, 59701
      • Saint James Community Hospital and Cancer Treatment Center
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Berdeaux, Donald MD (UIA Investigator)
    • Havre, Montana, United States, 59501
      • Northern Montana Hospital
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59801
      • Community Medical Hospital
    • Missoula, Montana, United States, 59802
      • Montana Cancer Specialists
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14623
      • Interlakes Foundation Inc-Rochester
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Independence, Ohio, United States, 44131
      • Cleveland Clinic Cancer Center Independence
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic Wooster Specialty Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee - Knoxville
  • Washington
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison Bremerton Hematology and Oncology
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology and Oncology PLLC
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital
    • Poulsbo, Washington, United States, 98370
      • Harrison Poulsbo Hematology and Oncology
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98112
      • Group Health Cooperative
    • Seattle, Washington, United States, 98122
      • The Polyclinic
    • Sedro-Woolley, Washington, United States, 98284
      • United General Hospital
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology PS
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Medical Center
  • Wyoming
    • Casper, Wyoming, United States, 82609
      • Rocky Mountain Oncology
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Treatment (lenalidomide); 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; Given orally; Other Names: CC-5013; IMiD-1; Revlimid

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mikkael Sekeres, Southwest Oncology Group

Publications and helpful links

General Publications

• Sekeres MA, Gundacker H, Lancet J, Advani A, Petersdorf S, Liesveld J, Mulford D, Norwood T, Willman CL, Appelbaum FR, List AF. A phase 2 study of lenalidomide monotherapy in patients with deletion 5q acute myeloid leukemia: Southwest Oncology Group Study S0605. Blood. 2011 Jul 21;118(3):523-8. doi: 10.1182/blood-2011-02-337303. Epub 2011 May 6.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (ACTUAL): July 1, 2011
• Study Completion (ACTUAL): July 1, 2011

Study Registration Dates

• First Submitted: July 13, 2006
• First Submitted That Met QC Criteria: July 13, 2006
• First Posted (ESTIMATE): July 14, 2006

Study Record Updates

• Last Update Posted (ACTUAL): February 11, 2022
• Last Update Submitted That Met QC Criteria: January 13, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukocyte Disorders; Eosinophilia; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Monocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Hypereosinophilic Syndrome; Leukemia, Basophilic, Acute; Leukemia, Eosinophilic, Acute; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: NCI-2009-00785 (REGISTRY: CTRP (Clinical Trial Reporting Program)); U10CA032102 (U.S. NIH Grant/Contract); SWOG-S0605; CDR0000484449; S0605 (OTHER: CTEP)