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Clinical Trial 19201

Cancer Type: Malignant Hematology
Interventions:Placebo; gilteritinib

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Joseph Pidala

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase III Trial of the FLT3 Inhibitor Gilteritinib Administered as Maintenance Therapy Following Allogeneic Transplant for Patients with FLT3/ITD AML

Summary

The main purpose of this study is to learn if it is safe and effective (works well) to treat participants who have FLT3/ITD AML with a study drug called gilteritinib (ASP2215) after transplant. Investigators want to know if this study drug works better than a placebo (pill that contains no drug, like a sugar pill) to stop the AML from coming back.

Objective

The primary objective is to compare relapse free survival (RFS) between participants with FLT3/ITD AML in CR1 who undergo HCT and are randomized to receive gilteritinib or placebo beginning after the time of engraftment for a two year period. Secondary Objectives: 1. To determine the safety and tolerability of gilteritinib after HCT. 2. To compare overall survival (OS), non-relapse mortality (NRM) and event-free survival (EFS) (where events include relapse, death, stopping therapy and administration of donor lymphocyte infusion (DLI) or new therapy for suspicion of disease)in participants treated with gilteritinib as maintenance therapy after HCT compared to those treated with placebo. 3. To compare 6-month cumulative incidence of grade II-IV and III-IV aGVHD and 12-month and 24-moth cumulative incidence of mild, moderate, and severe GVHD in participants treated with gilteritinib as maintenance therapy after HCT compared to those treated with placebo. 4. To examine the effect of pre- and post transplant MRD on RFS and OS.

Inclusion Criteria

  • Potential participant is considered a suitable candidate for HCT and has an acceptable source of allogeneic donor cells, as defined per institutional practice (allogeneic HCT for any donor source [matched sibling, unrelated donor (URD), mismatched URD, related haploidentical, or umbilical cord blood] and any graft source [umbilical cord, BM, peripheral blood (PB)], and any conditioning [myeloablative conditioning (MAC), reduced intensity conditioning (RIC), or non-myeloablative conditioning (NMA)] will be permitted).
  • Considered a legal adult by local regulation at the time of signing informed consent form (ICF).
  • Consents to allow access to diagnostic BM aspirate or PB sample and/or the DNA derived from that sample, if available, that may be used to validate a companion diagnostic that is being developed in parallel with gilteritinib.
  • Has confirmed, morphologically documented AML in CR1. For the purposes of registration, CR1 will be defined as less than 5% blasts in the BM with no morphologic characteristics of acute leukemia (e.g., Auer Rods) in the BM with no evidence of extramedullary disease such as central nervous system involvement or granulocytic sarcoma.
  • Has not received more than 2 cycles of induction chemotherapy to achieve CR1. The induction cycles can be the same regimen or different regimens. The regimen(s) may contain conventional agents, investigational agents, or a combination of both.
  • Participants with CR with incomplete count recovery (CRp or CRi) are allowed. Incomplete platelet recovery (CRp) is defined as CR with platelet count less than 100 x 10^9/L. Incomplete blood count recovery (CRi) is defined as CR with residual neutropenia less than 1 x 1^09/L with or without complete platelet recovery. Red blood cell count (RBC) and platelet transfusion independence is not required.
  • Maximum time allowed from establishment of CR1 to registration is 12 months.
  • Has presence of the FLT3/ITD activating mutation in the BM or PB as determined by the local institution at diagnosis.
  • Must meet clinical laboratory test requirements as outlined in the study documentation
  • Has left ventricular ejection fraction (LVEF) at rest ≥ 40%.
  • Has diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) ≥ 50% predicted and/or forced expiratory volume in 1 second (FEV1) ≥ 50% predicted.
  • Female participants must either: Be of non-childbearing potential; Or, if of childbearing potential, Agree not to try to become pregnant during the study for 6 months after the final study drug administration and have a negative serum pregnancy test at screening. And, if heterosexually active, agree to consistently use highly effective contraception per locally accepted standards in addition to a barrier method starting at screening and throughout the study period and for 6 months after the final study drug administration. Female participants must agree not to breastfeed or donate ova throughout the study drug treatment period and for 6 months after the final study drug administration.
  • Male participants (even if surgically sterilized), and partners who are women of childbearing potential must be using highly effective contraception in addition to a barrier method throughout the study drug treatment period and for 127 days after the final study drug administration. Male participants must not donate sperm throughout the study drug treatment period and for 127 days after the final study drug administration.
  • Participant is able to take an oral medication.
  • Participant agrees not to participate in another interventional study while on treatment.
  • Additional criteria may apply

  • Exclusion Criteria

  • Potential participant has had a prior allogeneic transplant.
  • Karnofsky performance status score less than 70%
  • Requires treatment with concomitant drugs that are strong inducers of CYP3A within 14 days of start of study drug.
  • Requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the participant.
  • Has a Fridericia-corrected QT interval (QTcF) > 450 msec (average of triplicate determinations) per central read.
  • Has long QT Syndrome at screening.
  • Known infection with human immunodeficiency virus (HIV).
  • Active hepatitis B infection as determined by nucleic acid amplification test ( NAAT) or surface antigen assay. Participants who have acquired immunity from past exposure (HBcAb positive / HBsAb positive / HBsAg negative) are eligible.
  • Active hepatitis C infection as determined by NAAT. NAAT must be performed if the participant has positive serology for hepatitis C. Participants who have had past exposure and have no detectable virus either through spontaneous clearance or treatment are eligible.
  • An uncontrolled infection. If a bacterial or viral infection is present, the participant must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to registration. If a fungal infection is present, the participant must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to registration.
  • Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection.
  • Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
  • Has had a myocardial infarction within 6 months prior to registration or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia.
  • A serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Breast feeding or pregnant.
  • Prior malignancies, except lobular breast carcinoma in situ, fully resected basal cell or squamous cell carcinoma of skin or treated cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent less than 5 years previously will not be allowed.
  • Additional criteria may apply