Acute Myeloid Leukemia Clinical Trial
— RADIUSOfficial title:
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
Verified date | March 2021 |
Source | Novartis |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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,
Status | Completed |
Enrollment | 60 |
Est. completion date | April 30, 2018 |
Est. primary completion date | April 30, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility | Inclusion Criteria: - 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 Exclusion Criteria: 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) - Patients with any pulmonary infiltrate including those suspected to be of infectious origin (unless resolves to = Grade 1 within screening timeframe) - Patient required treatment with strong CYP3A4 inhibitors or moderate or strong CYP3A4 inducers other than those required for GVH or infection prophylaxis or treatment Pregnant or nursing (lactating) women, or women of child-bearing potential, must have used highly effective methods of contraception during dosing and for 30 days after treatment completion |
Country | Name | City | State |
---|---|---|---|
Canada | Novartis Investigative Site | Toronto | Ontario |
United States | Northside Hospital | Atlanta | Georgia |
United States | University of North Carolina at Chapel Hill University of North Carolina 6 | Chapel Hill | North Carolina |
United States | University of Chicago Medical Center | Chicago | Illinois |
United States | University Hospitals Case Medical Center | Cleveland | Ohio |
United States | Baylor Health Care System/Sammons Cancer Center Oncology | Dallas | Texas |
United States | SCRI- Colorado Blood Cancer Institute | Denver | Colorado |
United States | Karmanos Cancer Institute Karmanos - Wayne State | Detroit | Michigan |
United States | Hackensack University Medical Center Hackensack Univ Med Ctr (32) | Hackensack | New Jersey |
United States | University of California San Diego Moores Cancer Center | La Jolla | California |
United States | University of California at Los Angeles Oncology | Los Angeles | California |
United States | Tennessee Oncology Sarah Cannon Research Inst. | Nashville | Tennessee |
United States | Vanderbilt Univeristy Oncology | Nashville | Tennessee |
United States | Oregon Health Sciences University | Portland | Oregon |
United States | Mayo Clinic - Rochester | Rochester | Minnesota |
United States | Washington University School Of Medicine-Siteman Cancer Ctr Washington U School of Med | Saint Louis | Missouri |
United States | Texas Transplant Physicians Group Oncology 2 | San Antonio | Texas |
United States | Fred Hutchinson Cancer Research Center Oncology | Seattle | Washington |
United States | H Lee Moffitt Cancer Center and Research Institute Oncology | Tampa | Florida |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
United States, Canada,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 18 Months (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. | Randomization to 18 months | |
Secondary | Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis | DFS was defined as the time from transplant to relapse or death due to any cause. If a patient had more than 1 event (e.g., relapse then death) then the earliest date was taken into account. | date of transplant up to 24 months | |
Secondary | Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis | Relapse-free survival was defined as the time from transplant to relapse or death due to the disease 24 months post-transplant. If a patient had more than one event (e.g., relapse then death) then the earliest date was taken into account. | date of transplant up to 24 months | |
Secondary | Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | Overall survival was defined as the time from transplant to death due to any cause. | date of transplant up to 24 months | |
Secondary | Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis | Non-relapse mortality (NRM) was defined as the time from transplant to death due to reasons other than relapse/progressive disease | date of transplant up to 24 months | |
Secondary | FLT3-ITD Mutation Status Centrally in Archived Material From Diagnosis (if Available) Including Mutant:Wild Type Ratio. | Unable to retrieve a sufficient amount of archived samples to perform an analysis therefore the study was not able to verify the FLT3-ITD mutation status | up to 24 months from date of transplannt or at study completion | |
Secondary | Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels | Pre-dose levels (Cmin) will be directly determined from raw plasma concentration-time data. Values below the lower limit of quantification (LLOQ) will be treated as zero in any calculations of summary statistics. | Pre-dose on days 1 and 15 of Cycle 1, on day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 |
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