Gemtuzumab Ozogamicin With G-CSF, Cladribine, Cytarabine and Mitoxantrone in Treating Participants With Previously Untreated Acute Myeloid Leukemia or High-Grade Myeloid Neoplasm

NCT03531918

Last updated date
Study Location
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Acute Myeloid Leukemia, High-Grade Myeloid Neoplasm, Blasts 10 Percent or More of Bone Marrow Nucleated Cells, Blasts 10 Percent or More of Peripheral Blood White Cells, High Grade Myeloid Neoplasm
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

- Diagnosis of untreated "high-grade" myeloid neoplasm (≥ 10% blasts in blood or bone marrow) or acute myeloid leukemia (AML) other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016 World Health Organization (WHO) classification; outside diagnostic material is acceptable to establish diagnosis; submission of peripheral blood specimen for flow cytometry performed at the study institution should be considered; diagnostic material must have been submitted for cytogenetic and/or molecular testing as clinically appropriate

- Medically fit, as defined by treatment-related mortality (TRM) score ≤13.1 calculated with simplified model

- The use of hydroxyurea prior to study registration is allowed; patients with symptoms/signs of hyperleukocytosis or white blood cells (WBC) > 100,000/uL can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m^2/dose) prior to enrollment

- Patients may have received low-intensity treatment (e.g. azacitidine/decitabine, lenalidomide, growth factors) for antecedent low-grade myeloid neoplasm (i.e. < 10% blasts in blood and bone marrow)

- Bilirubin ≤ 2.5 x institutional upper limit of normal (IULN) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (assessed within 14 days prior to study day 0)

- Serum creatinine ≤ 2.0 mg/dL (assessed within 14 days prior to study day 0)

- Left ventricular ejection fraction ≥ 45%, assessed within 12 months prior to study day 0, e.g. by multigated acquisition (MUGA) scan or echocardiography, or other appropriate diagnostic modality and no clinical evidence of congestive heart failure

- Women of childbearing potential and men must agree to use adequate contraception

- Provide written informed consent

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


- Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not
considered candidate for tyrosine kinase inhibitor treatment


- Concomitant illness associated with a likely survival of < 1 year


- Active systemic fungal, bacterial, viral, or other infection, unless disease is under
treatment with anti-microbials, and/or controlled or stable (e.g. if specific,
effective therapy is not available/feasible or desired [e.g. known chronic viral
hepatitis, human immunodeficiency virus (HIV)]); patient needs to be clinically stable
as defined as being afebrile and hemodynamically stable for 24 hours; patients with
fever thought to be likely secondary to leukemia are eligible


- Known hypersensitivity to any study drug


- Confirmed or suspected pregnancy or active breast feeding


- Treatment with any other investigational anti-leukemia agent; in phase 2, treatment
with a tyrosine kinase inhibitor for patients with FLT3-mutated AML is permissible

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Acute Myeloid Leukemia, High-Grade Myeloid Neoplasm, Blasts 10 Percent or More of Bone Marrow Nucleated Cells, Blasts 10 Percent or More of Peripheral Blood White Cells, High Grade Myeloid NeoplasmGemtuzumab Ozogamicin With G-CSF, Cladribine, Cytarabine and Mitoxantrone in Treating Participants With Previously Untreated Acute Myeloid Leukemia or High-Grade Myeloid Neoplasm
NCT03531918
  1. Seattle, Washington
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Gemtuzumab Ozogamicin With G-CSF, Cladribine, Cytarabine and Mitoxantrone in Treating Participants With Previously Untreated Acute Myeloid Leukemia or High-Grade Myeloid Neoplasm
Official Title  ICMJE A Single-Center Phase 1/2 Study of Single- or Fractioned-Dose Gemtuzumab Ozogamicin in Combination With G-CSF, Cladribine, Cytarabine and Mitoxantrone (GCLAM) for Previously Untreated Adult Acute Myeloid Leukemia or High-Grade Myeloid Neoplasm
Brief Summary This phase I/II trial studies the side effects and best dosing frequency of gemtuzumab ozogamicin when given in combination with granulocyte colony stimulating factor (G-CSF), cladribine, cytarabine and mitoxantrone (GCLAM) and to see how well they work in treating participants with acute myeloid leukemia or high-grade myeloid tumors (neoplasms) that have not been previously treated. Antibody-drug conjugates, such as gemtuzumab ozogamicin, act by directly delivering toxic chemotherapy to cancer cells. Granulocyte colony stimulating factor is a growth factor used to stimulate leukemia cells and render them more sensitive to chemotherapy drugs. Drugs used in chemotherapy, such as cladribine, cytarabine and mitoxantrone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving gemtuzumab ozogamicin in combination with G-CSF, cladribine, cytarabine and mitoxantrone hydrochloride may work better in treating participants with acute myeloid leukemia or high-grade myeloid neoplasm.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD) of gemtuzumab ozogamicin (GO) when added to GCLAM in patients with newly-diagnosed AML requiring induction chemotherapy. (Phase I) II. To evaluate the 6-month event-free survival (EFS) rate with GO + GCLAM treated at the MTD. (Phase II)

SECONDARY OBJECTIVES:

I. Describe, within the limits of a phase 1/2 study, the toxicity profile of the study regimen.

II. Compare, within the limits of a phase 1/2 study, measurable residual disease (MRD) rates with GO + GCLAM at the MTD to patients treated previously with GCLAM alone.

III. Estimate, within the limits of a phase 1/2 study, the relationship between MRD status after induction therapy and relapse risk/time to relapse as well as relapse-free and overall survival.

IV. Compare, within the limits of a phase 1/2 study, complete remission rates with GO + GCLAM at the MTD to patients treated previously with GCLAM alone.

V. Compare, within the limits of a phase 1/2 study, overall survival rates with GO + GCLAM at the MTD to patients treated previously with GCLAM alone VI. Evaluate, within the limits of a phase 1/2 study, the impact of GO dosing regimens on the duration of cytopenias.

VII. Collect biological specimens for use for the future laboratory investigation of biomarkers for response to GO.

OUTLINE: This is a phase I dose escalation study of gemtuzumab ozogamicin followed by a phase II study.

INDUCTION THERAPY: Participants receive gemtuzumab ozogamicin intravenously (IV) either as a single dose on day 1, or as three doses on days 1, 4, and 7. Participants also receive G-CSF subcutaneously (SC) on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, and mitoxantrone hydrochloride IV on days 1-3. Patients who do not achieve a CR or CRi following the first course of induction are eligible for a second course, which is given without gemtuzumab ozogamicin. Participants with a complete remission (CR) or complete remission with incomplete count recovery (CRi) may then proceed to Post-Remission Therapy.

POST-REMISSION THERAPY: Participants receive G-CSF, cladribine, and cytarabine as in Induction Therapy during course 1, and cytarabine IV every 12 hours on days 1-6 of courses 2-3. Treatment repeats every month for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up every 3 months for 5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia
  • High-Grade Myeloid Neoplasm
  • Blasts 10 Percent or More of Bone Marrow Nucleated Cells
  • Blasts 10 Percent or More of Peripheral Blood White Cells
  • High Grade Myeloid Neoplasm
Intervention  ICMJE
  • Drug: Cladribine
    Given IV
    Other Names:
    • 2-CdA
    • 2CDA
    • CdA
    • Cladribina
    • Leustat
    • Leustatin
    • Leustatine
    • RWJ-26251
  • 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: 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
  • Biological: Granulocyte Colony-Stimulating Factor
    Given SC
    Other Names:
    • Colony Stimulating Factor 3
    • Colony-Stimulating Factor (Granulocyte)
    • Colony-Stimulating Factor 3
    • CSF3
    • G CSF
    • G-CSF
    • Granulocyte Colony Stimulating Factor
    • Pluripoietin
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Mitoxantrone Hydrochloride
    Given IV
    Other Names:
    • CL 232315
    • DHAD
    • DHAQ
    • Dihydroxyanthracenedione Dihydrochloride
    • Mitoxantrone Dihydrochloride
    • Mitoxantroni Hydrochloridum
    • Mitozantrone Hydrochloride
    • Mitroxone
    • Neotalem
    • Novantrone
    • Onkotrone
    • Pralifan
Study Arms  ICMJE Experimental: Treatment (GO, GCLAM)

INDUCTION THERAPY: Participants receive gemtuzumab ozogamicin IV either as a single dose on day 1, or as three doses on days 1, 4, and 7. Participants also receive G-CSF SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, and mitoxantrone hydrochloride IV on days 1-3. Patients who do not achieve a CR or CRi following the first course of induction are eligible for a second course, which is given without gemtuzumab ozogamicin. Participants with a CR or CRi may then proceed to Post-Remission Therapy.

POST-REMISSION THERAPY: Participants receive G-CSF, cladribine, and cytarabine as in Induction Therapy during course 1, and cytarabine IV every 12 hours on days 1-6 of courses 2-3. Treatment repeats every month for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Interventions:
  • Drug: Cladribine
  • Drug: Cytarabine
  • Drug: Gemtuzumab Ozogamicin
  • Biological: Granulocyte Colony-Stimulating Factor
  • Other: Laboratory Biomarker Analysis
  • Drug: Mitoxantrone Hydrochloride
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: May 9, 2018)
72
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2025
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of untreated "high-grade" myeloid neoplasm (? 10% blasts in blood or bone marrow) or acute myeloid leukemia (AML) other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016 World Health Organization (WHO) classification; outside diagnostic material is acceptable to establish diagnosis; submission of peripheral blood specimen for flow cytometry performed at the study institution should be considered; diagnostic material must have been submitted for cytogenetic and/or molecular testing as clinically appropriate
  • Medically fit, as defined by treatment-related mortality (TRM) score ?13.1 calculated with simplified model
  • The use of hydroxyurea prior to study registration is allowed; patients with symptoms/signs of hyperleukocytosis or white blood cells (WBC) > 100,000/uL can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m^2/dose) prior to enrollment
  • Patients may have received low-intensity treatment (e.g. azacitidine/decitabine, lenalidomide, growth factors) for antecedent low-grade myeloid neoplasm (i.e. < 10% blasts in blood and bone marrow)
  • Bilirubin ? 2.5 x institutional upper limit of normal (IULN) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (assessed within 14 days prior to study day 0)
  • Serum creatinine ? 2.0 mg/dL (assessed within 14 days prior to study day 0)
  • Left ventricular ejection fraction ? 45%, assessed within 12 months prior to study day 0, e.g. by multigated acquisition (MUGA) scan or echocardiography, or other appropriate diagnostic modality and no clinical evidence of congestive heart failure
  • Women of childbearing potential and men must agree to use adequate contraception
  • Provide written informed consent

Exclusion Criteria:

  • Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for tyrosine kinase inhibitor treatment
  • Concomitant illness associated with a likely survival of < 1 year
  • Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials, and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired [e.g. known chronic viral hepatitis, human immunodeficiency virus (HIV)]); patient needs to be clinically stable as defined as being afebrile and hemodynamically stable for 24 hours; patients with fever thought to be likely secondary to leukemia are eligible
  • Known hypersensitivity to any study drug
  • Confirmed or suspected pregnancy or active breast feeding
  • Treatment with any other investigational anti-leukemia agent; in phase 2, treatment with a tyrosine kinase inhibitor for patients with FLT3-mutated AML is permissible
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03531918
Other Study ID Numbers  ICMJE 10000
NCI-2018-00776 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
10000 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
RG9218023 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
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
Plan to Share IPD:No
Responsible Party Fred Hutchinson Cancer Research Center
Study Sponsor  ICMJE Fred Hutchinson Cancer Research Center
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Pfizer
Investigators  ICMJE
Principal Investigator:Roland WalterFred Hutch/University of Washington Cancer Consortium
PRS Account Fred Hutchinson Cancer Research Center
Verification Date September 2020

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