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

NCT ID: NCT01883362

Last Updated: 2021-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-06
• Study Completion Date: 2018-04-30

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,

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Standard of Care with Midostaurin

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).

Group Type: EXPERIMENTAL

Midostaurin

Intervention Type: DRUG

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

Patients received standard of care alone in the post SCT setting

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: OTHER

Standard of Care was not defined per protocol. The investigator prescribed based on the commonly used medications given in the post SCT setting.

Interventions

Midostaurin

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.

Intervention Type: DRUG

Standard of Care

Standard of Care was not defined per protocol. The investigator prescribed based on the commonly used medications given in the post SCT setting.

Intervention Type: OTHER

Other Intervention Names

PKC412

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian Elliott, MD

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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

SCRI- Colorado Blood Cancer Institute

Denver, Colorado, United States

H Lee Moffitt Cancer Center and Research Institute Oncology

Tampa, Florida, United States

Northside Hospital

Atlanta, Georgia, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Karmanos Cancer Institute Karmanos - Wayne State

Detroit, Michigan, United States

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Washington University School Of Medicine-Siteman Cancer Ctr Washington U School of Med

St Louis, Missouri, United States

Hackensack University Medical Center Hackensack Univ Med Ctr (32)

Hackensack, New Jersey, United States

University of North Carolina at Chapel Hill University of North Carolina 6

Chapel Hill, North Carolina, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Oregon Health Sciences University

Portland, Oregon, United States

Tennessee Oncology Sarah Cannon Research Inst.

Nashville, Tennessee, United States

Vanderbilt Univeristy Oncology

Nashville, Tennessee, United States

Baylor Health Care System/Sammons Cancer Center Oncology

Dallas, Texas, United States

Texas Transplant Physicians Group Oncology 2

San Antonio, Texas, United States

Fred Hutchinson Cancer Research Center Oncology

Seattle, Washington, United States

Novartis Investigative Site

Toronto, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 33288862 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CPKC412AUS23

Identifier Type: -

Identifier Source: org_study_id