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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01358734
• Other study ID #: CC-5013-AML-001
• Status: Completed
• Phase: Phase 2
• Start date: April 27, 2012
• Est. completion date: May 15, 2018

Study information

• Verified date: June 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: May 15, 2018
• Est. primary completion date: May 19, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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 10?/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

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Azacitidine
Azacitidine at 75 mg/m^2/day subcutaneous on Days 1-7
• 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:
• 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

Locations

Country	Name	City	State
Canada	(402) Tom Baker Cancer Centre	Calgary	Alberta
Canada	(405) University of Alberta Hospital	Edmonton	Alberta
Canada	(403) Queen Elizabeth II Health Sciences Centre - VG Site	Halifax	Nova Scotia
Canada	(404) The Ottawa Hospital	Ottawa	Ontario
Canada	(400) Princess Margaret Hospital	Toronto	Ontario
Canada	(401) Cancer Care Manitoba	Winnipeg	Manitoba
United States	(115) University of Colorado Anschultz Cancer Center	Aurora	Colorado
United States	(150) Billings Clinic	Billings	Montana
United States	(140) Rush University Medical Center	Chicago	Illinois
United States	(105) University of Texas Southwestern Medical Center Simmons Comprehensive Cancer Center	Dallas	Texas
United States	(205) Greenville Hospital System	Greenville	South Carolina
United States	(180) University of California, San Diego	La Jolla	California
United States	(240) Cedars-Sinai Medical Center	Los Angeles	California
United States	(175) University Lousiville	Louisville	Kentucky
United States	(135) University of Wisconsin	Madison	Wisconsin
United States	(145) Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	(235) University of Minnesota	Minneapolis	Minnesota
United States	(230) Tennessee Oncology, PLLC	Nashville	Tennessee
United States	(195) Tulane University Hospital Tulane Cancer Center	New Orleans	Louisiana
United States	(165) Mount Sinai Medical Center New York	New York	New York
United States	(215) Hematology Oncology Medical Group	Orange	California
United States	(160) The Western Pennsylvania Hospital- Cancer Institute	Pittsburgh	Pennsylvania
United States	(130) UC Davis Medical Center	Sacramento	California
United States	(100) Washington University School of Medicine	Saint Louis	Missouri
United States	(155) Cancer Care Centers of South Texas	San Antonio	Texas
United States	(200) Coastal Integrative Cancer Care	San Luis Obispo	California
United States	(120) Avera Cancer Institute	Sioux Falls	South Dakota
United States	(125) University of Stanford	Stanford	California
United States	(210) University of Arizona Cancer Center	Tucson	Arizona
United States	(185) The University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants Alive at One Year	Defined as the percentage of participants who survived at one year	Up to 12 months
Primary	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
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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