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NCT01883362 · CITED IN SOURCE DOCUMENTS

Standard of Care +/- Midostaurin to Prevent Relapse Post Stem Cell Transplant in Patients With FLT3-ITD Mutated AML

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2021-03-17

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,

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis

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outcome · POSTED

Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 18 Months (Full Analysis Set) by Kaplan-Meier Analysis

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outcome · POSTED

Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis

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outcome · POSTED

Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis

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outcome · POSTED

Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis

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outcome · POSTED

Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis

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outcome · POSTED

FLT3-ITD Mutation Status Centrally in Archived Material From Diagnosis (if Available) Including Mutant:Wild Type Ratio.

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outcome · POSTED

Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels

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outcome · POSTED

All Collected Deaths

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
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
healthy Volunteers
false
maximum Age
70 Years
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients received standard of care in the post stem cell transplant (SCT) setting in addition to Midostaurin 50mg twice a day for 12 months (cycles).
    intervention Names
    1. Drug: Midostaurin
    label
    Standard of Care with Midostaurin
    type
    EXPERIMENTAL
  2. description
    Patients received standard of care alone in the post SCT setting
    intervention Names
    1. Other: Standard of Care
    label
    Standard of Care
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Standard of Care with Midostaurin
    description
    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.
    name
    Midostaurin
    other Names
    1. PKC412
    type
    DRUG
  2. arm Group Labels
    1. Standard of Care
    description
    Standard of Care was not defined per protocol. The investigator prescribed based on the commonly used medications given in the post SCT setting.
    name
    Standard of Care
    type
    OTHER
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
PREVENTION
Enrollment
count
60
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Proportion of Participants With Relapse Free Survival (RFS) up to 18 Months Post Transplant (Full Analysis Set) by Kaplan-Meier Analysis
    time Frame
    date of transplant up to 18 months
secondary Outcomes
  1. description
    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.
    measure
    Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 18 Months (Full Analysis Set) by Kaplan-Meier Analysis
    time Frame
    Randomization to 18 months
  2. description
    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.
    measure
    Proportion of Participants With Relapse Free Survival (RFS) - Time From Randomization up to 24 Months(Full Analysis Set) by Kaplan-Meier Analysis
    time Frame
    date of transplant up to 24 months
  3. description
    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.
    measure
    Proportion of Participants With Relapse Free Survival (RFS) - Time From Transplant (Full Analysis Set) by Kaplan-Meier Analysis
    time Frame
    date of transplant up to 24 months
  4. description
    Overall survival was defined as the time from transplant to death due to any cause.
    measure
    Probability of Overall Survival - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis
    time Frame
    date of transplant up to 24 months
  5. description
    Non-relapse mortality (NRM) was defined as the time from transplant to death due to reasons other than relapse/progressive disease
    measure
    Probability of Non-relapse Mortality (NRM) - Date of Transplant up to 24 Months (Full Analysis Set) by Kaplan-Meier Analysis
    time Frame
    date of transplant up to 24 months
  6. description
    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
    measure
    FLT3-ITD Mutation Status Centrally in Archived Material From Diagnosis (if Available) Including Mutant:Wild Type Ratio.
    time Frame
    up to 24 months from date of transplannt or at study completion
  7. description
    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.
    measure
    Plasma Pharmacokinetics (PK) of Midostaurin and the Metabolites: CGP62221 and CGP52421: Pre-dose Levels
    time Frame
    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
Full study description
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,
Source references
references
  1. citation
    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
    33288862
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        y or transplant in a separate phase II study.[<a href="#cit/section_5.18">18</a>]</p></li><li> In the multicenter, randomized phase II <a href="/clinicaltrials/NCT01883362">RADIUS</a> trial (NCT01883362), the addition of midostaurin to standard of care was compared with standard of care alone after allogeneic HCT.[<a href="#cit/s
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        hase II study.[<a href="#cit/section_5.18">18</a>]</p></li><li> In the multicenter, randomized phase II <a href="/clinicaltrials/NCT01883362">RADIUS</a> trial (NCT01883362), the addition of midostaurin to standard of care was compared with standard of care alone after allogeneic HCT.[<a href="#cit/section_5.19">19</a>] Similar to
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      1. context
        Updated: March 14, 2025
        datetime
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        display
        March 14, 2025

    Preserved source evidence · Not medical advice