A Study of Lenalidomide in Pediatric Subjects With Relapsed or Refractory Acute Myeloid Leukemia
A Phase 2, Multicenter, Single-arm, Open-label Study to Evaluate the Activity, Safety and Pharmacokinetics of Lenalidomide (Revlimid®) in Pediatric Subjects From 1 to = 18 Years of Age With Relapsed or Refractory Acute Myeloid Leukemia.
1 other identifier
interventional
17
2 countries
62
Brief Summary
To determine the activity of lenalidomide in the treatment of pediatric subjects with relapsed/refractory acute myeloid leukemia (AML) (with second or greater relapse or refractory to at least 2 prior induction attempts) measured by morphological complete response defined as either a CR or CRi within the first 4 cycles of treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Nov 2015
Typical duration for phase_2
62 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 25, 2015
CompletedFirst Posted
Study publicly available on registry
September 2, 2015
CompletedStudy Start
First participant enrolled
November 19, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 22, 2017
CompletedResults Posted
Study results publicly available
September 20, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
January 11, 2019
CompletedJanuary 7, 2020
December 1, 2019
1.7 years
August 25, 2015
July 13, 2018
December 17, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants Who Achieved a Morphologic Complete Response Within the First Four Cycles of Lenalidomide Treatment According to the Modified International Working Group (IWG) Criteria
The morphological complete response rate was defined as the total number of participants with morphological CR observed within the first 4 cycles of lenalidomide (regardless of whether the CR/CRi was observed at the end of Cycle 1, 2, 3 or 4) over the total number of participants evaluable for this endpoint. According to Modified IWG criteria, morphologic CR was defined as: 1. Absolute neutrophil count (ANC) ≥ 1000/μL and platelets ≥ 100,000 without transfusions and/or exogenous growth factor support (i.e., no transfusion or exogenous growth factor within 7 days of assessment; 2. Bone marrow \< 5% blasts evidence of trilineage hematopoiesis; 3. No evidence of extramedullary disease. Morphologic CRi was defined as: 1. ANC \< 1000/μL and platelets \< 100,000/μL or \> 100,000/μL without platelet recovery (requiring transfusion within 7 days of assessment); 2. BM with \< 5% blasts and evidence of trilineage hematopoiesis; 3. No evidence of extramedullary disease.
From day of the first dose of IP to end of cycle 4; Response was assessed at the completion of the 21-day treatment period of cycles 1, 2, 3, and 4 and at treatment discontinuation.
Secondary Outcomes (15)
Number of Participants Who Achieved a Bone Marrow Confirmed CR/CRi Lasting 3 Months (Durable Response Rate)
From date of confirmed complete response observed until treatment failure or worse; up to data cut-off date of 31 December 2017
Duration of Response
From date of first time of complete response observed until treatment failure or worse; up to data cut-off date of 31 December 2017
Number of Participants Who Achieved a Best Response of Morphologic Complete Remission, Morphologic Complete Remission Incomplete or Partial Remission
Response was assessed at the completion of the 21-day treatment period of cycles 1, 2, 3.
Number of Participants With a Morphologic CR, CRi, PR or Treatment Failure at Cycles 1, 2 and 3
Response was assessed at the completion of the 21-day treatment period of cycles 1, 2, 3.
Number of Participants Who Received a Haematopoietic Stem Cell Transplant (HSCT)
From first dose of study drug up to 5 years post HSCT
- +10 more secondary outcomes
Study Arms (1)
Lenalidomide
EXPERIMENTALLenalidomide API will administered at a starting dose of 2 mg/kg/day. Lenalidomide will be provided as either a capsule (2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg or 25 mg) or as an oral suspension (10mg/mL).
Interventions
Lenalidomide will be administered orally once daily for the first 21 days of every 28-day cycle. The starting dose will be 2 mg/kg/day with a maximum dose of 70 mg/day. Number of cycles: 12, or until evidence of progressive disease. Participants will also be discontinued if unresolved toxicities as described in the protocol occur, or if dose reductions are required and subject does not tolerate minimum dose level of 1mg/kg/day.
Eligibility Criteria
You may qualify if:
- \- Participants must satisfy the following criteria to be enrolled in the study:
- Male or female is 1 to ≤ 18 years of age at the time of signing the Informed Consent Form / Informed Assent Form (ICF/IAF).
- Participants (when applicable, parental/legal representative) must understand and voluntarily provide permission to the ICF/IAF prior to conducting any study-related assessments/procedures.
- Participants have relapsed or refractory acute myeloid leukemia after at least 2 prior induction attempts:
- Bone marrow aspirate or biopsy must have ≥ 5% blasts by morphology and/or flow cytometry.
- Each block of chemotherapy is a separate reinduction attempt.
- Donor lymphocyte infusion (DLI) is considered a reinduction attempt.
- Participants are willing and able to adhere to the study visit schedule and other protocol requirements.
- Participants have a Karnofsky score of ≥ 50% (participants ≥ 16 years of age) or a Lansky score ≥ 50% (participants \< 16 years of age).
- Participants have a resting left ventricular ejection fraction (LVEF) of ≥ 40% obtained by echocardiography.
- Participants have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to first dose. All prior treatment-related toxicities must have resolved to ≤ Grade 2 prior to enrollment.
- Regarding radiation therapy, time elapsed prior to first dose of lenalidomide:
- weeks for local palliative radiation therapy (XRT).
- weeks if prior craniospinal chemoradiation therapy (CRT) or if ≥ 50% radiation of pelvis.
- weeks if other bone marrow radiation has been administered.
- +23 more criteria
You may not qualify if:
- Participants have Down syndrome.
- Participants have French-American-British classification (FAB) type M3 leukemia (acute promyelocytic leukemia) or identification of t(15;17).
- Participants have isolated central nervous system (CNS) involvement or extramedullary relapse. (Participants with combined CNS/marrow relapse may be enrolled).
- Participants had prior treatment with cytotoxic chemotherapy within 2 weeks of the first dose of lenalidomide with the exception of hydroxyurea (allowed prior to the first dose of lenalidomide and through Day 14 of Cycle 1) and intrathecal (IT) cytarabine will be administered within 2 weeks prior to administration of lenalidomide.
- Participants have had prior treatment with biologic antineoplastic agents less than 7 days before the first dose of lenalidomide. For agents that have known adverse events (AEs) occurring beyond 7 days after administration (ie, monoclonal antibodies), this period must be extended beyond the time during which acute AEs are known to occur.
- Participants have had prior treatment with lenalidomide.
- Participant is pregnant or lactating.
- Participants have an uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment).
- Participants has known Human Immunodeficiency Virus (HIV) positivity (participants who are receiving antiretroviral therapy for HIV disease).
- Participants have a prior history of malignancies other than AML unless the subject has been free of the disease for ≥ 5 years from first dose of lenalidomide.
- The presence of any of the following will exclude a participant from enrollment:
- Participants have any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study.
- Participants have any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study.
- Participants have any condition that confounds the ability to interpret data from the study.
- Participants have cardiac disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version 4.03 Grade 3 or 4).
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Celgenelead
Study Sites (62)
Children's Hospital
Birmingham, Alabama, 35294, United States
Phoenix Childrens Hospital
Phoenix, Arizona, 85016, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202, United States
Miller Children's Hospital
Long Beach, California, 90806, United States
Children's Hospital of Los Angeles
Los Angeles, California, 90027, United States
Southern California Permanente Medical Group
Los Angeles, California, 90027, United States
Valley Children's Hospital
Madera, California, 93636, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Lucile Salter Packard Children's Hospital at Stanford
Palo Alto, California, 94304, United States
Loma Linda University
San Bernardino, California, 92408, United States
UCSF Children's Hospital
San Francisco, California, 94143, United States
Colorado Children's Hospital
Aurora, Colorado, 80045, United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
Alfred I Dupont Hospital For Children
Wilmington, Delaware, 19803, United States
Children's Hospital National Medical Center
Washington D.C., District of Columbia, 20010-2970, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908, United States
Nemours Children's Clinic
Jacksonville, Florida, 32207, United States
All Children's Hospital
St. Petersburg, Florida, 33701, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322, United States
Ann and Robert H Lurie Childrens Hospital of Chicago
Chicago, Illinois, 60611, United States
Advocate Chilldren's Hospital
Oak Lawn, Illinois, 60453, United States
Riley Hospital For Children at IU Health
Indianapolis, Indiana, 46202, United States
Kosair Children's Hospital
Louisville, Kentucky, 40202, United States
Children's Hospital New Orleans
New Orleans, Louisiana, 70118, United States
Johns Hopkins University
Baltimore, Maryland, 21287, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, 55404, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Children's Mercy Hospital
Kansas City, Missouri, 64108, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Children's Specialty Center of Nevada
Las Vegas, Nevada, 89109, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Morristown Memorial Hosp
Morristown, New Jersey, 07962, United States
Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Roswell Park Cancer Inst
Buffalo, New York, 14263, United States
Columbia University Medical Center
New York, New York, 10032, United States
University of Rochester Medical Center
Rochester, New York, 14642, United States
New York Medical College
Valhalla, New York, 10595, United States
University of North Carolina
Chapel Hill, North Carolina, 27599, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Legacy Emanuel Hospital and Health Center
Portland, Oregon, 97227, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
UPMC Childrens Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224, United States
Carolinas Healthcare System
Charleston, South Carolina, 28203, United States
Greenville Health System
Greenville, South Carolina, 29605, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37212, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75235, United States
Texas Children's Cancer Center
Houston, Texas, 77030, United States
Methodist Hospital
San Antonio, Texas, 78229, United States
Primary Children's Medical Center
Salt Lake City, Utah, 84113, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Midwest Children's Cancer Center
Milwaukee, Wisconsin, 53226, United States
Alberta Childrens Hospital
Calgary, Alberta, T3B 6A8, Canada
British Columbia Children's Hospital
Vancouver, British Columbia, V6H3V4, Canada
IWK Health Center
Halifax, Nova Scotia, B3K 6R8, Canada
Childrens Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1, Canada
McGill University Health Center
Montreal, Quebec, H4A 3J1, Canada
Hospital For Sick Children
Torento, M5G 1X8, Canada
Related Publications (1)
O'Brien MM, Alonzo TA, Cooper TM, Levine JE, Brown PA, Slone T, August KJ, Benettaib B, Biserna N, Poon J, Patturajan M, Chen N, Simcock M, Zimmerman L, Kolb EA. Results of a phase 2, multicenter, single-arm, open-label study of lenalidomide in pediatric patients with relapsed or refractory acute myeloid leukemia. Pediatr Blood Cancer. 2021 Jul;68(7):e28946. doi: 10.1002/pbc.28946. Epub 2021 Mar 10.
PMID: 33694257DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The results of the efficacy analysis were reviewed by an independent Data Monitoring Committee, which concluded that the study would not proceed to Stage 2, given that the efficacy criteria for continuation of the study to Stage 2 had not been met.
Results Point of Contact
- Title
- Anne McClain, Senior Manager, Clinical Trial Disclosur
- Organization
- Celgene Corporation
Study Officials
- STUDY DIRECTOR
Bouchra Benettaib, MD
Celgene Corporation
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 25, 2015
First Posted
September 2, 2015
Study Start
November 19, 2015
Primary Completion
July 22, 2017
Study Completion
January 11, 2019
Last Updated
January 7, 2020
Results First Posted
September 20, 2018
Record last verified: 2019-12