Standard of Care +/- Midostaurin to Prevent Relapse Post Stem Cell Transplant in Patients With FLT3-ITD Mutated AML
RADIUS
A Phase II, Randomized Trial of Standard of Care, With or Without Midostaruin to Prevent Relapse Following Allogeneic Hematopoietic Stem Cell Transplantation in Patients With FLT3-ITD Mutated Acute Myeloid Leukemia
1 other identifier
interventional
60
2 countries
19
Brief Summary
To determine if the addition of midostaurin (PKC412) to Standard of Care (SOC) therapy reduces relapse in FLT3-ITD mutated AML patients receiving an allogenetic hematopoietic stem cell transplant,
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Feb 2014
Typical duration for phase_2
19 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 25, 2013
CompletedFirst Posted
Study publicly available on registry
June 21, 2013
CompletedStudy Start
First participant enrolled
February 6, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2018
CompletedResults Posted
Study results publicly available
March 17, 2021
CompletedMarch 17, 2021
March 1, 2021
4.2 years
March 25, 2013
April 29, 2019
March 12, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis
Relapse-free survival assesses the clinical benefit of remaining in remission free from relapse or death due to the disease. It was defined as the time from transplant to relapse or death due to the disease. Relapse following complete response was defined as reappearance of leukemic blasts in the peripheral blood or finding more than 5% blasts in the bone marrow.
date of transplant up to 18 months
Secondary Outcomes (7)
Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 18 Months (Full Analysis Set) by Kaplan-Meier Analysis
Randomization to 18 months
Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis
date of transplant up to 24 months
Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis
date of transplant up to 24 months
Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis
date of transplant up to 24 months
Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis
date of transplant up to 24 months
- +2 more secondary outcomes
Study Arms (2)
Standard of Care with Midostaurin
EXPERIMENTALPatients received standard of care in the post stem cell transplant (SCT) setting in addition to Midostaurin 50mg twice a day for 12 months (cycles).
Standard of Care
ACTIVE COMPARATORPatients received standard of care alone in the post SCT setting
Interventions
Midostaurin was supplied in 25mg soft gelatin capsule taken orally twice a day for 28 days of each cycle. Patients will be treated for 12 cycles.
Standard of Care was not defined per protocol. The investigator prescribed based on the commonly used medications given in the post SCT setting.
Eligibility Criteria
You may qualify if:
- Patients between 18 and 70 years of age
- Patients with ECOG Performance Status of ≤ 2
- Patients with a documented unequivocal diagnosis of AML according to WHO 2008 classification (\>20% blasts in the bone marrow), excluding M3 (acute promyelocytic leukemia).
- Patients with a documented FLT3 ITD mutation, determined by local laboratory for eligibility (historical tissue will be requested for central analysis confirmation)
- Patients who undersent allogeneic HSCT in CR1 from a matched related or matched unrelated donor. All of the following criteria had to be met: HLA typing to include available 8/8 or 7/8 allele HLA matched donor (at A,B,C, DRB1) Single allelic mismatch allowed
- Patients who had received a conditioning regimen which included one of the following:
- Busulfan/Fludarabine (Bu/Flu) Busulfan (16 mg/kg PO or 12.8 mg/kg IV) Fludarabine (120-180 mg/m2) Fludarabine / Melphalan (Flu/Mel) Fludarabine (120-180 mg/m2) Melphalan (≤ 150 mg/m2) Busulfan/Cyclophosphamide (Bu/Cy) Busulfan (16 mg/kg PO or 12.8 mg/kg IV) Cyclophosphamide (120 mg/kg) Cyclophosphamide/Total Body Irradiation (Cy/TBI) Cyclophosphamide (120 mg/kg) TBI (1200-1420 cGy)
- Recovery of counts by day 42 and was able to start midostaurin by day 60 post-HSCT (first dose of midostaurin to start no earlier than 28 days post-HSCT); ANC \>1000µL, platelets ≥20,000 without platelet transfusion
You may not qualify if:
- Patients eligible for this study must not have met any of the following criteria:
- Patients who failed prior attempts at allogeneic HSCT
- Patients who had received an autologous transplant
- Patients with Acute GVHD Grade III-IV
- Patients with a known confirmed diagnosis of HIV infection or active viral hepatitis.
- Impaired cardiac function including any of the following:
- Screening ECG with a QTc \> 450 msec. If QTc \> 450 and electrolytes were not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc.
- Patients with congenital long QT syndrome
- History or presence of sustained ventricular tachycardia
- Any history of ventricular fibrillation or torsades de pointes
- Bradycardia defined as HR. \< 50 bpm
- Right bundle branch block + left anterior hemiblock (bifascicular block)
- Patients with myocardial infarction or unstable angina \< 6 months prior to starting study
- Congestive Heart Failure NY Heart Association class III or IV
- Patients with an ejection fraction \< 45% assessed by MUGA or ---ECHO within 28 days prior to starting study cycle 1 (of midostaurin or control group)
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (19)
University of California San Diego Moores Cancer Center
La Jolla, California, 92093-0987, United States
University of California at Los Angeles Oncology
Los Angeles, California, 90095, United States
SCRI- Colorado Blood Cancer Institute
Denver, Colorado, 80218, United States
H Lee Moffitt Cancer Center and Research Institute Oncology
Tampa, Florida, 33612, United States
Northside Hospital
Atlanta, Georgia, 30342, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
Karmanos Cancer Institute Karmanos - Wayne State
Detroit, Michigan, 48201, United States
Mayo Clinic - Rochester
Rochester, Minnesota, 55905, United States
Washington University School Of Medicine-Siteman Cancer Ctr Washington U School of Med
St Louis, Missouri, 63110, United States
Hackensack University Medical Center Hackensack Univ Med Ctr (32)
Hackensack, New Jersey, 07601, United States
University of North Carolina at Chapel Hill University of North Carolina 6
Chapel Hill, North Carolina, 27599-9500, United States
University Hospitals Case Medical Center
Cleveland, Ohio, 44106, United States
Oregon Health Sciences University
Portland, Oregon, 97239, United States
Tennessee Oncology Sarah Cannon Research Inst.
Nashville, Tennessee, 37203, United States
Vanderbilt Univeristy Oncology
Nashville, Tennessee, 37232, United States
Baylor Health Care System/Sammons Cancer Center Oncology
Dallas, Texas, 75246, United States
Texas Transplant Physicians Group Oncology 2
San Antonio, Texas, 78229, United States
Fred Hutchinson Cancer Research Center Oncology
Seattle, Washington, 98109, United States
Novartis Investigative Site
Toronto, Ontario, M5G 2M9, Canada
Related Publications (1)
Maziarz RT, Levis M, Patnaik MM, Scott BL, Mohan SR, Deol A, Rowley SD, Kim DDH, Hernandez D, Rajkhowa T, Haines K, Bonifacio G, Rine P, Purkayastha D, Fernandez HF. Midostaurin after allogeneic stem cell transplant in patients with FLT3-internal tandem duplication-positive acute myeloid leukemia. Bone Marrow Transplant. 2021 May;56(5):1180-1189. doi: 10.1038/s41409-020-01153-1. Epub 2020 Dec 7.
PMID: 33288862DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Brian Elliott, MD
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 25, 2013
First Posted
June 21, 2013
Study Start
February 6, 2014
Primary Completion
April 30, 2018
Study Completion
April 30, 2018
Last Updated
March 17, 2021
Results First Posted
March 17, 2021
Record last verified: 2021-03