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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01358734
First received: May 19, 2011
Last updated: May 25, 2016
Last verified: May 2016
  Purpose
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).

Condition Intervention Phase
Acute Myeloid Leukemia
Acute Myelogenous Leukemia
Drug: Azacitidine
Drug: Lenalidomide
Other: Best Supportive Care (BSC)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Kaplan Meier Estimates for One Year Survival [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Overall Survival (OS) was defined as the time from randomization to death from any cause. OS was calculated using the date of randomization and date of death, or date of last follow-up for censored participants.


Secondary Outcome Measures:
  • Remission Rate (CR + CRi) [ Time Frame: Up to 74 months ] [ Designated as safety issue: No ]
    Remission Rate was defined as CR + CRi). Morphologic complete remission (CR) was defined as a leukemia-free state defined as less than 5% blasts in a bone marrow aspirate with bone marrow spicules and with at least 200 nucleated cells (there should be no blasts with Auer rods or persistence of extra-medullary disease) AND an absolute neutrophil count (ANC) of > 1 x 10^9/L, a platelet count ≥ 100 x 10^9/L, and Red Blood Cell transfusion (RBC) independence (no RBC transfusions for 1 week before each assessment). Morphologic complete remission with incomplete blood count recovery (CRi) was defined as a morphologic complete remission but the ANC (Absolute Neutrophil Count) may be < 1 x 10^9/L or plateletsmay be < 100 x 10^9/L.

  • Duration of Remission (DoR) [ Time Frame: Up to 74 months ] [ Designated as safety issue: No ]
    Duration of remission defined as the time from the date a response of CR or CRi is first documented until the date the participant has documented relapse after CR or CRi or dies from any cause, whichever occurs first.

  • Cytogenetic Complete Remission Rate (CRc) [ Time Frame: Up to 74 months ] [ Designated as safety issue: No ]
    The CRc response category is comprised of the subset of participants who had abnormal ctyogenetics 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

  • Percentage of Participants With an Overall Response Rate (CR +CRi+ PR) [ Time Frame: Up to 74 months ] [ Designated as safety issue: No ]
    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 an absolute neutrophil count (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 (CRi) is 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 (PR) is 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).

  • Progression-Free Survival (PFS) [ Time Frame: Up to 74 months ] [ Designated as safety issue: No ]
    PFS is defined as the time from randomization to the first observation of documented disease progression or death due to any cause whichever occurs first.

  • Event-Free Survival (EFS) [ Time Frame: Up to 74 months ] [ Designated as safety issue: No ]
    EFS is 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 occurs first

  • Relapse-Free Survival (RFS) [ Time Frame: Up to 74 months ] [ Designated as safety issue: No ]
    Relapse-free survival is defined only for participants who achieve a CR or CRi and is measured as the interval from the date of first documented leukemia-free state (defined as less than 5% blasts in an aspirate sample) to the date of leukemia relapse, death from any cause, whichever occurs first, censoring at the last visit date for participants alive in continuous CR or CRi.

  • Percentage of Participants With 30-day Treatment-related Mortality [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    30-day mortality rate is defined as death from any cause within 30 days after first dose.

  • Number of Participants With Treatment Emergent Adverse Events (TEAE) [ Time Frame: Up to data cut-off of 01 May 2015; 36 months and 4 days ] [ Designated as safety issue: Yes ]
    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


Other Outcome Measures:
  • Percentage of Participants Alive at One Year [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    Percentage of participants who survived at one year


Enrollment: 88
Study Start Date: April 2012
Estimated Study Completion Date: April 2018
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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:
  • Revlimid®
  • CC-5013
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:
  • Revlimid®
  • CC-5013
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 Name: 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


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.
  Eligibility

Ages Eligible for Study:   65 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01358734

  Show 30 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Robert Gale, MD Celgene
  More Information

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01358734     History of Changes
Other Study ID Numbers: CC-5013-AML-001 
Study First Received: May 19, 2011
Results First Received: April 4, 2016
Last Updated: May 25, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
AML
elderly
acute myelogenous leukemia
vidaza
azacitidine
elderly AML
revlimid
lenalidomide

Additional relevant MeSH terms:
Lenalidomide
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Thalidomide
Azacitidine
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 23, 2016