A Study Being Conducted at Multiple Locations to Compare Safety and Efficacy of Three Different Regimens; (1) High-Dose Lenalidomide; (2) Lenalidomide + Azacitidine; or (3) Azacitidine in Subjects ≥ 65 Years With Newly-Diagnosed Acute Myeloid Leukemia

A Phase 2, Multicenter, Randomized, Open-label, Parallel-group Study of a Lenalidomide (Revlimid®) Regimen or a Sequential Azacitidine (Vidaza®) Plus Lenalidomide (Revlimid®) Regimen Versus an Azacitidine (Vidaza®) Regimen for Therapy of Older Subjects With Newly Diagnosed Acute Myeloid Leukemia

The study aim is to compare safety and efficacy of high-dose lenalidomide regimen, sequential azacitidine and lenalidomide and an azacitidine in persons ≥65 years with newly-diagnosed acute myeloid leukemia (AML).

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Acute Myelogenous Leukemia
• Intervention / Treatment: Drug: Azacitidine; Drug: Lenalidomide; Other: Best Supportive Care (BSC)

Detailed Description

On September 11, 2013, randomization into the continuous 50 mg lenalidomide only arm was temporarily suspended based on review of the data from the first 13 participants and a high rate of discontinuation (11/13 participants). The Data Monitoring Committee assessed the study data on September 20, 2013 and reported no safety concerns. The high rate of early discontinuation is inconsistent with the treatment duration required for testing the study primary endpoint of survival at one year. Consequently, Celgene has decided not to reopen the lenalidomide only arm.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • (402) Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z1
      • (405) University of Alberta Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • (401) Cancer Care Manitoba
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • (403) Queen Elizabeth II Health Sciences Centre - VG Site
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • (404) The Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 2M9
      • (400) Princess Margaret Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • (210) University of Arizona Cancer Center
  • California
    • La Jolla, California, United States, 92093-0960
      • (180) University of California, San Diego
    • Los Angeles, California, United States, 90048
      • (240) Cedars-Sinai Medical Center
    • Orange, California, United States, 92868
      • (215) Hematology Oncology Medical Group
    • Sacramento, California, United States, 95857
      • (130) UC Davis Medical Center
    • San Luis Obispo, California, United States, 93401
      • (200) Coastal Integrative Cancer Care
    • Stanford, California, United States, 94305
      • (125) University of Stanford
  • Colorado
    • Aurora, Colorado, United States, 80045
      • (115) University of Colorado Anschultz Cancer Center
  • Florida
    • Miami Beach, Florida, United States, 33140
      • (145) Mount Sinai Comprehensive Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • (140) Rush University Medical Center
  • Kansas
    • Westwood, Kansas, United States, 66205
      • (185) The University of Kansas Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • (175) University Lousiville
  • Louisiana
    • New Orleans, Louisiana, United States, 70072
      • (195) Tulane University Hospital Tulane Cancer Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • (235) University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1093
      • (100) Washington University School of Medicine
  • Montana
    • Billings, Montana, United States, 59101
      • (150) Billings Clinic
  • New York
    • New York, New York, United States, 10029-65749
      • (165) Mount Sinai Medical Center New York
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224-1791
      • (160) The Western Pennsylvania Hospital- Cancer Institute
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • (205) Greenville Hospital System
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • (120) Avera Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • (230) Tennessee Oncology, PLLC
  • Texas
    • Dallas, Texas, United States, 75390-9179
      • (105) University of Texas Southwestern Medical Center Simmons Comprehensive Cancer Center
    • San Antonio, Texas, United States, 78229
      • (155) Cancer Care Centers of South Texas
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • (135) University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newly diagnosed acute myeloid leukemia (AML), AML with antecedent hematologic disorder or therapy-related AML
• Male or female subjects aged ≥ 65
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• White blood cell (WBC) count ≤ 10 x 10⁹/L at screening

Exclusion Criteria:

• Previous treatment with azacitidine, decitabine, cytarabine or lenalidomide
• Previous cytotoxic or biologic treatment of any kind for AML or prior use of targeted therapy agents.
• Suspected or proven acute promyelocytic leukemia
• Prior bone marrow or stem cell transplantation
• Candidate for allogeneic bone marrow or stem cell transplantation
• AML antecedent hematologic disorder such as chronic myelogenous leukemia or myeloproliferative neoplasms
• Presence of malignant disease within the previous 12 months with exceptions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenalidomide in combination with azacitidine; Repeated cycles of azacitidine 75 mg/m^2/day subcutaneous (SC) on Days 1-7 and lenalidomide 50 mg/day by mouth (PO) on Days 8-28 followed by a 14-day break plus best supportive care	Drug: Azacitidine; Azacitidine at 75 mg/m^2/day subcutaneous on Days 1-7; Other Names: Vidaza; Drug: Lenalidomide; Lenalidomide 50 mg PO daily x 28 days for the first 2 cycles then 25 mg PO daily x 28 days for the next 2 cycles followed by continuous 28-day cycles of lenalidomide 10 mg PO daily; Other Names: CC-5013; Revlimid®; Other: Best Supportive Care (BSC); The use of BSC was considered as concomitant treatment and must be documented as concomitant medication. BSC includes, but is not limited to, treatment with Red Blood Celll (RBC) or whole blood transfusions, fresh frozen plasma transfusions, platelet transfusions, antibiotic or antifungal therapy, and nutritional support
Experimental: Lenalidomide - single agent; Lenalidomide 50 mg PO daily for 28 days for the first 2 cycles and lenalidomide 25 mg daily for 28 days for the next 2 cycles followed by continuous 28-day cycles of lenalidomide 10 mg daily PO plus best supportive care	Drug: Lenalidomide; Lenalidomide 50 mg PO daily x 28 days for the first 2 cycles then 25 mg PO daily x 28 days for the next 2 cycles followed by continuous 28-day cycles of lenalidomide 10 mg PO daily; Other Names: CC-5013; Revlimid®; Other: Best Supportive Care (BSC); The use of BSC was considered as concomitant treatment and must be documented as concomitant medication. BSC includes, but is not limited to, treatment with Red Blood Celll (RBC) or whole blood transfusions, fresh frozen plasma transfusions, platelet transfusions, antibiotic or antifungal therapy, and nutritional support
Experimental: Azacitidine-single agent; Repeated cycles of azacitidine 75mg/m^2/day subcutaneous on Days 1-7 followed by a 21-day break plus best supportive care	Drug: Azacitidine; Azacitidine at 75 mg/m^2/day subcutaneous on Days 1-7; Other Names: Vidaza; Other: Best Supportive Care (BSC); The use of BSC was considered as concomitant treatment and must be documented as concomitant medication. BSC includes, but is not limited to, treatment with Red Blood Celll (RBC) or whole blood transfusions, fresh frozen plasma transfusions, platelet transfusions, antibiotic or antifungal therapy, and nutritional support

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kaplan Meier Estimates for One Year Survival	One-year survival rate was defined as all deaths within one year from the date of randomization. All others censored at the at year 1 or date of discontinuation	Up to 24 months
Overall Survival	Overall Survival reported at the end of the study are for those participants who were alive at the end of the study	From date of randomization until the date of the first documented date of progression or date of death of any cause; the overall median follow-up for survivng participants was 4.1 months (range 0.2 to 54.8 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Complete Response or Morphologic Incomplete Response.	Based on IWG response criteria for AML. Complete remission (CR), morphologic complete remission (CR) was defined as < 5% bone marrow blasts, an absolute neutrophil count ≥ 1 x 10^9/L, platelets ≥100 x 10^9/L, and transfusion independence (no transfusions for 1 week prior to each assessment). No duration of these findings is required for confirmation of this response. Morphologic CR with incomplete blood count recovery (CRi) was defined as a morphologic complete remission but the ANC count may be <1 x 10^9/L and/or the platelet count may be <100 x 10^9/L. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.	Complete Response or Morphologic Incomplete Response data not analyzed.
Duration of Remission (DoR)	Duration of remission was defined as the time from the date of CR or CRi until relapse. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.	Duration of Remission (DoR) time frame not analyzed.
Cytogenetic Complete Remission Rate (CRc)	The CRc response category is comprised of the subset of participants who had abnormal cytogenetics at baseline and subsequently achieved CR during treatment in conjunction with a reversion to a normal karyotype. For the primary definition of CRc, a normal karyotype is defined as no clonal abnormalities after review of at least 10 metaphases using conventional cytogenetic techniques. Cytogenetic complete remission rate (CRc) 1) CR criteria met AND 2) Abnormal karyotype present at baseline AND 3) Reversion to normal karyotype at time of CR (based on ≥ 10 metaphases), where date of cytogenetic sample = date of BM sample used for the CR assessment. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.	Cytogenetic Complete Remission timeframe was not analyzed.
Percentage of Participants With an Overall Response Rate (CR +CRi+ PR)	Morphologic complete remission (CR) is defined as a leukemia-free state defined as less than 5% blasts in a one marrow aspirate with spicules and with at least 200 nucleated cells (there should be no blasts with auer rods) and ANC of ≥ 1 x 10^9/L, a platelet count ≥ 100 x 10^9/L, no transfusions for 1 week prior to each assessment. No duration of these findings is required for confirmation of this response. Morphologic complete remission with incomplete blood count recovery was defined as a morphologic complete remission but the ANC may be < 1 x 10^9/L and/or the platelet count may be < 100 x 10^9/L. Partial remission was defined as an ANC > 1 x 10^9/L and platelet count ≥ 100 x 10^9/L with a > 50% decrease in the percentage of bone marrow blasts to 5% to 25% (a blast count value of ≤ 5% may also be considered a partial remission if auer rods are present). Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.	Overall response rate time frame was not analyzed.
Progression-Free Survival (PFS)	PFS is defined as the time from randomization to the first observation of documented disease progression or death from any cause whichever occurred first. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.	Progression-Free survival data and time frame was not analyzed.
Event-Free Survival (EFS)	EFS was defined as the interval from the date of randomization to the date of treatment failure, progressive disease, relapse after CR or CRi, or death from any cause, whichever occurred first. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.	Event-Free survival time was not analyzed.
Relapse-Free Survival (RFS)	RFS is defined only for subjects that achieve CR and CRi and is measured as the interval from that date to the date of disease relapse, death from any cause, whichever occurs first, censoring at the last visit date for subjects alive in continuous CR/CRi. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.	Relapse-Free survival time frame was not analyzed.
Percentage of Participants With 30-Day Treatment-Related Mortality	30-day mortality rate was defined as death from any cause within 30 days after first dose.	30 days
Number of Participants With Treatment Emergent Adverse Events (TEAE)	TEAEs were defined as those events that started on or after the first day of study drug up until 28 days after the last dose of study drug; Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability; is a congenital anomaly/birth defect; constitutes an important medical event. Severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); and according to the scale: Grade (Gr) 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death	From the first dose of study drug up to 28 days after the last dose of study drug; up to 15 May 2018
Number of Participants With a Second Primary Malignancy	Second primary malignancies were monitored as events of interest and reported as serious adverse events regardless of the treatment arm the participant was enrolled in.	From randomization of the last participant up to a minimum of 4 years following discontinuation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Alive at One Year	Defined as the percentage of participants who survived at one year	Up to 12 months

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Robert Gale, MD, Celgene

Publications and helpful links

General Publications

• Medeiros BC, McCaul K, Kambhampati S, Pollyea DA, Kumar R, Silverman LR, Kew A, Saini L, Beach CL, Vij R, Wang X, Zhong J, Gale RP. Randomized study of continuous high-dose lenalidomide, sequential azacitidine and lenalidomide, or azacitidine in persons 65 years and over with newly-diagnosed acute myeloid leukemia. Haematologica. 2018 Jan;103(1):101-106. doi: 10.3324/haematol.2017.172353. Epub 2017 Nov 2.

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2012
• Primary Completion (Actual): May 19, 2015
• Study Completion (Actual): May 15, 2018

Study Registration Dates

• First Submitted: May 19, 2011
• First Submitted That Met QC Criteria: May 20, 2011
• First Posted (Estimate): May 24, 2011

Study Record Updates

• Last Update Posted (Actual): June 25, 2019
• Last Update Submitted That Met QC Criteria: June 17, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: lenalidomide; elderly; AML; azacitidine; acute myelogenous leukemia; revlimid; vidaza; elderly AML
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Azacitidine
• Other Study ID Numbers: CC-5013-AML-001