Trial Search Results

A Trial of the FMS-like Tyrosine Kinase 3 (FLT3) Inhibitor Gilteritinib Administered as Maintenance Therapy Following Allogeneic Transplant for Patients With FLT3/Internal Tandem Duplication (ITD) Acute Myeloid Leukemia (AML)

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy that confers a generally poor prognosis and FMS-like tyrosine kinase 3 (FLT3) receptor is the most common lesion. While survival rates are improving, relapse post-allogenic stem cell transplant remains a challenge.The study seeks to evaluate the efficacy of maintenance therapy with Gilteritinib in the FLT3/ITD AML population by way by measuring the duration of relapse free survival (RFS).

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Astellas Pharma Global Development, Inc.

Collaborator: Blood and Marrow Transplant Clinical Trials Network

Intervention(s):

  • Drug: gilteritinib
  • Drug: Placebo

Phase:

Phase 3

Eligibility


Registration Inclusion Criteria

   - Participant is considered a suitable candidate for HCT and has an acceptable source of
   allogeneic donor stem 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).

   - Participant is considered a legal adult by local regulation at the time of signing
   informed consent form (ICF).

   - Participant 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.

   - Participant has confirmed, morphologically documented AML in CR1. For the purposes of
   registration, CR1 will be defined as < 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.

      - Participant 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 < 100 x
      109/L. Incomplete blood count recovery (CRi) is defined as CR with residual
      neutropenia < 1 x 109/L with or without complete platelet recovery. Red blood
      cell count (RBC) and platelet transfusion independence is not required.

      - The maximum time allowed from establishment of CR1 to registration is 12 months.

   - Participant has presence of the FLT3/ITD activating mutation in the BM or PB as
   determined by the local institution at diagnosis.

   - Participant must meet the following criteria as indicated on the clinical laboratory
   tests:

      - Serum creatinine within normal range, or if serum creatinine outside normal
      range, then glomerular filtration rate (GFR) > 40 mL/min/1.73m2 as calculated
      with the Cockcroft-Gault equation with adjustment if total body weight is ≥ 125%
      of ideal body weight.

      - Total bilirubin (TBL) ≤ 2.5 mg/dL, except for participants with Gilbert's
      syndrome.

      - Serum AST and/or alanine aminotransferase (ALT) < 3 x institutional upper limit
      of normal (ULN).

   - Participant has left ventricular ejection fraction at rest ≥ 40%.

   - Participant 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:

      - postmenopausal (defined as at least 1 year without menses) prior to screening or

      - documented as surgically sterilized (at least 1 month prior to the screening
      visit)

   - 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.

      - For United Kingdom sites:

      - Highly effective forms of birth control include:

      - Consistent and correct usage of established hormonal contraceptives that inhibit
      ovulation

      - Established intrauterine device (IUD) or intrauterine system (IUS)

   - 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.

      - For United Kingdom sites:

      - Highly effective forms of birth control include:

      - Consistent and correct usage of established hormonal contraceptives that inhibit
      ovulation

      - Established IUD or IUS

      - Vasectomy (A vasectomy is a highly effective contraception method provided the
      absence of sperm has been confirmed. If not, an additional highly effective
      method of contraception should be used.)

      - Male is sterile due to a bilateral orchiectomy

   - 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.

Randomization Inclusion Criteria

   - Participant is ≥ 30 days and ≤ 90 days from hematopoietic cell infusion.

   - Participant has achieved engraftment. Engraftment is defined as ANC ≥ 500 cells/μL and
   platelets ≥ 20000/μL on 3 consecutive measurements (each occurring at least 1 day
   apart). The participant must not have had a platelet transfusion within 7 days prior
   to the first measurement.

   - Participant has confirmed ongoing morphologically documented AML in CR1. For the
   purposes of randomization, CR1 will be defined as < 5% blasts 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.

   - Participant meets the following criteria as indicated on the clinical laboratory
   tests:

      - Serum creatinine within normal range, or if serum creatinine outside normal
      range, then GFR > 40 mL/min/1.73m2 as calculated with the Cockcroft-Gault
      equation with adjustment if total body weight is ≥ 125% of ideal body weight.

      - TBL < 2.5 mg/dL, except for participants with Gilbert's syndrome.

      - Serum AST and/or ALT < 3 x institutional ULN.

      - Serum potassium and magnesium ≥ the institutional lower limit of normal (LLN).

   - If the participant has developed overall grades II-IV acute GVHD, the following
   criteria must be met to be randomized:

      - No requirement of > 0.5 mg/kg of prednisone (or equivalent) daily dose within 1
      week of randomization

      - No escalation of systemic immunosuppression in terms of increase of
      corticosteroids or addition of new agent / modality within 2 weeks of
      randomization. (Note that increasing calcineurin inhibitors or sirolimus to
      achieve therapeutic trough levels is allowed.) Topical skin and topical
      gastrointestinal steroids are allowed.

   - Participant is able to take oral medication.

Registration Exclusion Criteria

   - Participant has had a prior allogeneic transplant.

   - Participant has Karnofsky performance status score < 70% .

   - Participant requires treatment with concomitant drugs that are strong inducers of
   CYP3A within 14 days of start of study drug.

   - Participant 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.

   - Participant has a Fridericia-corrected QT interval (QTcF) > 450 msec (average of
   triplicate determinations) per central read.

   - Participant has long QT Syndrome at screening.

   - Participant has a known infection with human immunodeficiency virus (HIV).

   - Participant has active hepatitis B infection as determined by NAAT or surface antigen
   assay. Participants who have acquired immunity from past exposure (HBcAb positive /
   HBsAb positive / HBsAg negative) are eligible.

   - Participant has 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.

   - Participant has 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.

   - Participant 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.

   - Participant has a serious medical or psychiatric illness likely to interfere with
   participation in this clinical study.

   - Participant is breast feeding or pregnant.

   - Participant has 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 < 5 years previously will not be allowed.

Randomization Exclusion Criteria

   - Participant requires treatment with concomitant drugs that are strong inducers of
   CYP3A within 14 days of starting study drug.

   - Participant requires treatment with concomitant drugs that target serotonin 5HT1R or
   5HT2BR or sigma nonspecific receptor with the exception of drugs that are considered
   by the investigator to be absolutely essential for the care of the participant and for
   which no acceptable alternative exists.

   - Participant has a QTcF interval > 450 msec (average of triplicate determinations) by
   central read.

   - Participant has a need for supplemental oxygen with the exception of using previously
   existing non-invasive continuous positive airway pressure (CPAP) at night.

   - Participant has used investigational agents within 4 weeks of randomization.

   - Participant has used experimental therapy for acute GVHD within 4 weeks of
   randomization. If unsure of the definition of "experimental", discussion with one of
   the protocol chairs is recommended.

   - Participant has 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 randomization. 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 randomization.

      - 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.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
CCTO
650-498-7061
Not Recruiting