Testing the Combination of Standard Induction Therapy With Gemtuzumab Ozogamicin and Midostaurin as a Novel Approach to Treating Patients With Newly Diagnosed FLT-3 Mutated Acute Myeloid Leukemia

NCT03900949

Last updated date
Study Location
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Contact
503-494-5058

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Acute Myeloid Leukemia
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Ability to understand and the willingness to sign a written informed consent document

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Newly diagnosed AML as confirmed by bone marrow and/or peripheral blood examination as indicated, with:

- Confirmed CD33 positivity, per institutional standards

- Presence of FLT3 internal tandem duplication (ITD) or tyrosine kinase domain (TKD) mutation as confirmed by next-generation sequencing (NGS) or other molecular method

- Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN; local laboratory)

- Alanine aminotransferase (ALT) < 2.5 x ULN

- Total bilirubin < 2 x ULN (except for patients with known Gilbert's syndrome)

- Calculated creatinine clearance (according to the Cockcroft-Gault equation) > 40 mL/min OR serum creatinine < 1.5 x the ULN

- Female patients of childbearing potential must agree to use adequate contraception (2 forms of contraception or abstinence) from the screening visit until 6 months following the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

- Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from the screening visit until 3 months following the last dose of study treatment. They must also refrain from sperm donation from the screening visit until 90 days following the last dose of study treatment

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement to
enter study)


- Acute promyelocytic leukemia (per World Health Organization classification)


- Active central nervous system (CNS) involvement by AML, as assessed at discretion of
principal investigator (PI) or treating physician and confirmed by lumbar puncture


- Except for hydroxyurea, no other prior systemic anti-AML therapies may have been
received prior to starting study therapy


- Known history of veno-occlusive disease


- Known active human immunodeficiency virus (HIV), active hepatitis B or active
hepatitis C infection


- Patients with the following will be excluded: uncontrolled intercurrent illness
including, but not limited to, symptomatic congestive heart failure, unstable angina
pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to
enrollment, New York Heart Association (NYHA) class III or IV heart failure, severe
uncontrolled ventricular arrhythmias


- Patients with uncontrolled infection will not be enrolled until infection is treated


- Any concurrent condition that, in the investigator's opinion, would jeopardize the
safety of the patient or compliance with the protocol


- Inability to take oral medication


- Hypersensitivity to any study agent, or its excipients, when administered alone


- Pregnancy or breastfeeding at the time of enrollment

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Advanced Information
Descriptive Information
Brief Title  ICMJE Testing the Combination of Standard Induction Therapy With Gemtuzumab Ozogamicin and Midostaurin as a Novel Approach to Treating Patients With Newly Diagnosed FLT-3 Mutated Acute Myeloid Leukemia
Official Title  ICMJE A Phase I Study to Evaluate the Safety and Tolerability of Gemtuzumab Ozogamicin and Midostaurin When Used in Combination With Standard Cytarabine and Daunorubicin Induction for Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia
Brief Summary This phase I study hopes to explore how safe and tolerable is the combination of gemtuzumab ozogamicin (GO) and midostaurin, with the standard induction therapy (cytarabine and daunorubicin) in patients with newly diagnosed FLT-3 mutated Acute Myeloid Leukemia (AML). GO is FDA approved for the treatment of adults with newly diagnosed CD33 positive AML and used in combination with chemotherapy, cytarabine and daunorubicin. Midostaurin is FDA approved for use with cytarabine and daunorubicin in patients with FLT3-mutated AML. By combining standard induction therapy with GO and midostaurin, our aim is to investigate a novel approach to treating patients with newly diagnosed FLT3-mutated AML.
Detailed Description

PRIMARY OBJECTIVE:

I. To assess the maximum tolerated dose (MTD) of combining gemtuzumab ozogamicin (GO) to the induction regimen of cytarabine and daunorubicin (DA) and midostaurin.

SECONDARY OBJECTIVES:

I. To assess the frequency of early death associated with study treatment. II. To evaluate the preliminary efficacy of the study treatment. III. To assess the safety profile of the study treatment.

EXPLORATORY OBJECTIVES:

I. Quantify CD33 expression on acute myeloid leukemia (AML) blasts. II. Determine the CD33 single-nucleotide polymorphism (SNP) status previously reported to correlate with response and correlate clinical outcomes of patients with the CD33 genotype.

OUTLINE: This is a dose finding study to identify the maximum tolerated dose (MTD) schedule of GO, and its safety and tolerability in combination with midostaurin in FLT3-mutated newly diagnosed AML patients.

INDUCTION THERAPY: Patients receive cytarabine intravenously (IV) on days 1-7, daunorubicin IV on days 1-3 and midostaurin 50mg orally (PO) twice daily (BID) on days 8-21. Patients also receive gemtuzumab ozogamicin IV either on day or days 1 and 4 or days 1, 4 and 7 depending on dose level in the absence of disease progression or unacceptable toxicity.

RE-INDUCTION THERAPY: Between days 14 and 21 of Induction Therapy, patients who achieve at least 5% bone marrow blasts after an optional bone marrow biopsy may receive a single 28-day cycle of cytarabine and daunorubicin with or without midostaurin per the treating physician. Patients who achieve a complete remission (CR) or complete remission with incomplete blood count recovery (CRi) may undergo allogeneic stem cell transplantation (SCT) or receive consolidation therapy.

CONSOLIDATION THERAPY:

PATIENTS < 60 YEARS: Patients receive high dose cytarabine (HiDAC) IV on days 1, 3, and 5 and gemtuzumab ozogamicin IV on day 1 of cycle 1 and midostaurin 50mg PO BID on days 8-21. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

PATIENTS >= 60 YEARS: Patients receive cytarabine (MiDAC) IV on days 1, 3, and 5 and gemtuzumab ozogamicin IV on day 1 of cycle 1 and midostaurin 50mg PO BID on days 8-21. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 24 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    Undergo allogeneic SCT
    Other Names:
    • Allogeneic Hematopoietic Cell Transplantation
    • Allogeneic Stem Cell Transplantation
    • HSC
    • HSCT
    • Stem Cell Transplantation, Allogeneic
  • Drug: Cytarabine
    Given IV
    Other Names:
    • .beta.-Cytosine arabinoside
    • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
    • 1-.beta.-D-Arabinofuranosylcytosine
    • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
    • 1-Beta-D-arabinofuranosylcytosine
    • 1.beta.-D-Arabinofuranosylcytosine
    • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
    • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
    • Alexan
    • Ara-C
    • ARA-cell
    • Arabine
    • Arabinofuranosylcytosine
    • Arabinosylcytosine
    • Aracytidine
    • Aracytin
    • Aracytine
    • Beta-Cytosine Arabinoside
    • CHX-3311
    • Cytarabinum
    • Cytarbel
    • Cytosar
    • Cytosine Arabinoside
    • Cytosine-.beta.-arabinoside
    • Cytosine-beta-arabinoside
    • Erpalfa
    • Starasid
    • Tarabine PFS
    • U 19920
    • U-19920
    • Udicil
    • WR-28453
  • Drug: Daunorubicin Hydrochloride
    Given IV
    Other Names:
    • Cerubidin
    • Cerubidine
    • Cloridrato de Daunorubicina
    • Daunoblastin
    • Daunoblastina
    • Daunoblastine
    • Daunomycin Hydrochloride
    • Daunomycin, hydrochloride
    • Daunorubicin.HCl
    • Daunorubicini Hydrochloridum
    • FI-6339
    • Ondena
    • RP-13057
    • Rubidomycin Hydrochloride
    • Rubilem
  • Drug: Gemtuzumab Ozogamicin
    Given IV
    Other Names:
    • Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody
    • CDP-771
    • CMA-676
    • gemtuzumab
    • hP67.6-Calicheamicin
    • Mylotarg
    • WAY-CMA-676
  • Drug: Midostaurin
    Given PO
    Other Names:
    • CGP 41251
    • CGP41251
    • N-Benzoyl-Staurosporine
    • N-Benzoylstaurosporine
    • PKC-412
    • PKC412
    • Rydapt
Study Arms  ICMJE Experimental: Treatment (gemtuzumab ozogamicin, cytarabine, daunorubicin)
INDUCTION THERAPY: Cytarabine intravenously (IV) on days 1-7, daunorubicin IV on days 1-3 and midostaurin 50 mg orally (PO) twice daily (BID) on days 8-21. Gemtuzumab ozogamicin IV may be given either on days 1, or days 1 and 4 or days 1, 4 and 7. RE-INDUCTION THERAPY: Between days 14 and 21 of Induction Therapy, patients may receive a single 28-day cycle of cytarabine and daunorubicin with or without midostaurin per the treating physician. Patients may also undergo allogeneic stem cell transplantation (SCT) or receive consolidation therapy. CONSOLIDATION THERAPY: PATIENTS < 60 YEARS: high dose cytarabine (HiDAC) IV on days 1, 3, and 5 and gemtuzumab ozogamicin IV on day 1 of cycle 1 and midostaurin 50 mg PO BID on days 8-21. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. PATIENTS >= 60 YEARS: Same as above except cytarabine (MiDAC) IV on days 1, 3, and 5 (see detailed description).
Interventions:
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
  • Drug: Cytarabine
  • Drug: Daunorubicin Hydrochloride
  • Drug: Gemtuzumab Ozogamicin
  • Drug: Midostaurin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 25, 2020)
24
Original Estimated Enrollment  ICMJE
 (submitted: April 1, 2019)
28
Estimated Study Completion Date  ICMJE January 1, 2025
Estimated Primary Completion Date January 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Ability to understand and the willingness to sign a written informed consent document
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Newly diagnosed AML as confirmed by bone marrow and/or peripheral blood examination as indicated, with:

    • Confirmed CD33 positivity, per institutional standards
    • Presence of FLT3 internal tandem duplication (ITD) or tyrosine kinase domain (TKD) mutation as confirmed by next-generation sequencing (NGS) or other molecular method
  • Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN; local laboratory)
  • Alanine aminotransferase (ALT) < 2.5 x ULN
  • Total bilirubin < 2 x ULN (except for patients with known Gilbert's syndrome)
  • Calculated creatinine clearance (according to the Cockcroft-Gault equation) > 40 mL/min OR serum creatinine < 1.5 x the ULN
  • Female patients of childbearing potential must agree to use adequate contraception (2 forms of contraception or abstinence) from the screening visit until 6 months following the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from the screening visit until 3 months following the last dose of study treatment. They must also refrain from sperm donation from the screening visit until 90 days following the last dose of study treatment

Exclusion Criteria:

  • Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement to enter study)
  • Acute promyelocytic leukemia (per World Health Organization classification)
  • Active central nervous system (CNS) involvement by AML, as assessed at discretion of principal investigator (PI) or treating physician and confirmed by lumbar puncture
  • Except for hydroxyurea, no other prior systemic anti-AML therapies may have been received prior to starting study therapy
  • Known history of veno-occlusive disease
  • Known active human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection
  • Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, severe uncontrolled ventricular arrhythmias
  • Patients with uncontrolled infection will not be enrolled until infection is treated
  • Any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol
  • Inability to take oral medication
  • Hypersensitivity to any study agent, or its excipients, when administered alone
  • Pregnancy or breastfeeding at the time of enrollment
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Uma M Borate, MD503-494-5058[email protected]
Contact: Basak Gokcora503-494-2929[email protected]
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03900949
Other Study ID Numbers  ICMJE STUDY00018684
NCI-2019-01726 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
STUDY00018684 ( Other Identifier: OHSU Knight Cancer Institute )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Uma Borate, OHSU Knight Cancer Institute
Study Sponsor  ICMJE OHSU Knight Cancer Institute
Collaborators  ICMJE
  • Fred Hutchinson Cancer Research Center
  • Oregon Health and Science University
  • Pfizer
Investigators  ICMJE
Principal Investigator:Uma M Borate, MDOHSU Knight Cancer Institute
PRS Account OHSU Knight Cancer Institute
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP