Phase 2
N=60
Standard of Care +/- Midostaurin to Prevent Relapse Post Stem Cell Transplant in Patients With FLT3-ITD Mutated AML
Acute Myeloid Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT01883362 ↗Enrolled (actual)
60
Serious AEs
40.0%
Results posted
Mar 2021
Primary outcome: Primary: Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis — 0.93; 0.93; 0.80; 0.93 proportion of participants — p=0.2655
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Midostaurin (Drug); Standard of Care (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Apr 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis |
0.93; 0.93; 0.80; 0.93; 0.76; 0.89 | 0.2655 |
| SECONDARY Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 18 Months (Full Analysis Set) by Kaplan-Meier Analysis |
0.93; 0.93; 0.80; 0.93; 0.76; 0.85 | 0.4297 |
| SECONDARY Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis |
0.90; 0.93; 0.77; 0.89; 0.69; 0.85 | 0.2424 |
| SECONDARY Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis |
0.93; 0.93; 0.80; 0.93; 0.76; 0.89 | 0.4297 |
| SECONDARY Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis |
0.96; 1.00; 0.89; 0.89; 0.76; 0.85 | 0.3418 |
| SECONDARY Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis |
0.96; 1.00; 0.96; 0.96; 0.92; 0.96 | 0.4169 |
| SECONDARY FLT3-ITD Mutation Status Centrally in Archived Material From Diagnosis (if Available) Including Mutant:Wild Type Ratio. |
— | — |
| SECONDARY Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels |
17.46; 0.00; 16.89; 932.46; 1572.69; 906.57 | — |
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,
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01883362). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.