Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Daunorubicin and Cytarabine With or Without Uproleselan in Treating Older Adult Patients With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03701308
Recruitment Status : Recruiting
First Posted : October 10, 2018
Last Update Posted : September 16, 2021
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE October 8, 2018
First Posted Date  ICMJE October 10, 2018
Last Update Posted Date September 16, 2021
Actual Study Start Date  ICMJE January 16, 2019
Estimated Primary Completion Date December 1, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 18, 2020)
  • Event-free survival (EFS) (Phase II) [ Time Frame: Up to 5 years ]
    EFS is defined as the time from the date of randomization to the first of failure to achieve a complete remission (CR)/ CR with incomplete blood count recovery (CRi) during induction, relapse, or death due to any cause, with patients last known to be alive and event-free censored at the date of last contact.
  • Overall survival (OS) (Phase III) [ Time Frame: Up to 5 years ]
    Will be measured from the date of randomization to death from any cause, with patients last known to be alive censored at the date of last contact.
Original Primary Outcome Measures  ICMJE
 (submitted: October 8, 2018)
  • Event-free survival (EFS) (Phase II) [ Time Frame: Up to 5 years ]
    EFS is defined as the time from the date of registration/randomization to the first of failure to achieve a complete remission (CR) during induction, relapse, or death due to any cause, with patients last known to be alive and event-free censored at the date of last contact.
  • Overall survival (OS) (Phase III) [ Time Frame: Up to 5 years ]
    Will be measured from the date of registration/randomization to death from any cause, with patients last known to be alive censored at the date of last contact.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2019)
  • EFS rate [ Time Frame: Up to 1 year ]
    Will be formally tested hierarchically in a confirmatory setting at an overall one sided alpha of 0.025 level at the same time as the primary endpoint. Both hazard ratio and p-value for EFS will be presented.
  • Impact of off-protocol transplantation [ Time Frame: Up to 5 years ]
    Sensitivity analyses will be conducted. In addition, the proportion of patients who received transplantation in the two arms will be summarized and compared using a chi-square test.
  • Consistency of the treatment effect among each subgroup [ Time Frame: From baseline up to 5 years ]
    Non-parametric methods such as Kaplan-Meier and log-rank tests will be used within each subgroup. Univariate/multivariate Cox models will be fit within each subgroups; hazard ratios will be used to quantify the treatment effect within each subgroup, along with the 95% confidence intervals.
  • Disease-free survival (DFS) [ Time Frame: Time from achieving a complete response to time of relapse or death, assessed up to 5 years ]
  • Complete remission (CR) and overall response rate [ Time Frame: Up to 5 years ]
  • Incidence of adverse events [ Time Frame: Up to 5 years ]
    Will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 5.0. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
  • Prediction of CR, EFS, DFS, and OS by pretreatment characteristics such as age, morphology, cytogenetics, immunophenotype, molecular genetic features, WBC count and hemogram, and performance status with clinical outcomes [ Time Frame: Up to 5 years ]
    The associations between these baseline factors and CR, EFS, DFS, and OS will be analyzed using Kaplan-Meier curves, log-rank test, contingency table and chi-square test whenever appropriate. Multivariable analysis including Cox proportional hazards models and logistic regression models will be used as well to evaluate the associations.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2018)
  • EFS rate [ Time Frame: Up to 1 year ]
    Will be formally tested hierarchically in a confirmatory setting at an overall one sided alpha of 0.025 level at the same time as the primary endpoint. Both hazard ratio and p-value for EFS will be presented.
  • Impact of off-protocol transplantation [ Time Frame: Up to 5 years ]
    Sensitivity analyses will be conducted. In addition, the proportion of patients who received transplantation in the two arms will be summarized and compared using a chi-square test.
  • Consistency of the treatment effect among each subgroup [ Time Frame: From baseline up to 5 years ]
    Non-parametric methods such as Kaplan-Meier and log-rank tests will be used within each subgroup. Univariate/multivariate Cox models will be fit within each subgroups; hazard ratios will be used to quantify the treatment effect within each subgroup, along with the 95% confidence intervals.
  • Disease-free survival (DFS) [ Time Frame: Time from achieving a complete response to time of relapse or death, assessed up to 5 years ]
  • Complete remission (CR) and overall response rate [ Time Frame: Up to 5 years ]
  • Incidence of adverse events assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 5.0 [ Time Frame: Up to 5 years ]
    The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
  • Prediction of CR, EFS, DFS, and OS by pretreatment characteristics such as age, morphology, cytogenetics, immunophenotype, molecular genetic features, WBC count and hemogram, and performance status with clinical outcomes [ Time Frame: Up to 5 years ]
    The associations between these baseline factors and CR, EFS, DFS, and OS will be analyzed using Kaplan-Meier curves, log-rank test, contigency table and chi-square test whenever appropriate. Multivariable analysis including Cox proportional hazards models and logistic regression models will be used as well to evaluate the associations.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Daunorubicin and Cytarabine With or Without Uproleselan in Treating Older Adult Patients With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy
Official Title  ICMJE A Randomized Phase II/III Study of Conventional Chemotherapy +/- Uproleselan (GMI-1271) in Older Adults With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy
Brief Summary This phase II/III trial studies how well daunorubicin and cytarabine with or without uproleselan works in treating older adult patients with acute myeloid leukemia receiving intensive induction chemotherapy. Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Uproleselan may prevent cancer from returning or getting worse. Giving daunorubicin and cytarabine with uproleselan may work better in treating patients with acute myeloid leukemia compared to daunorubicin and cytarabine alone.
Detailed Description

PRIMARY OBJECTIVES:

I. Compare the event-free survival (EFS) of daunorubicin, cytarabine plus uproleselan versus daunorubicin and cytarabine in subjects >= age 60 with previously untreated acute myeloid leukemia. (Phase II) II. Compare the overall survival (OS) of the daunorubicin, cytarabine plus uproleselan to daunorubicin and cytarabine in this patient population. (Phase III)

SECONDARY OBJECTIVES:

I. Determine the rates of complete remission (CR), complete remission with incomplete count recovery (CRi), complete remission with incomplete hematopoietic recovery (CRh) and cytogenetic complete remission (CCyR) for each chemotherapy regimen.

II. Determine the overall survival (OS), and remission duration of patients for each chemotherapy regimen.

III. Describe the frequency and severity of adverse events for patients for each chemotherapy regimen.

IV. Describe the interaction of pretreatment disease and patient characteristics including morphology, cytogenetics, molecular genetic features, white blood cell (WBC) count and hemogram, and performance status on clinical outcomes.

CORRELATIVE SCIENCE OBJECTIVES:

I. Correlate specific karyotype groups (normal or various primary and secondary chromosomal abnormalities) with clinical and laboratory parameters and with response rates, response duration, survival and cure in patients treated with various induction and post-induction regimens.

II. Correlate specific karyotype groups with selected molecular abnormalities and with measurable residual disease.

III. To determine karyotype changes at end of consolidation and the influence of the type of change (or no change) in karyotype at the end of consolidation on subsequent clinical course.

IV. To determine karyotype changes at relapse and the influence of the type of change (or no change) in karyotype at relapse on subsequent clinical course.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: INDUCTION: Patients receive daunorubicin intravenously (IV) on days 1-3 and cytarabine via continuous intravenous infusion (CIVI) over 168 hours on days 1-7. Patients with residual disease indicated by bone marrow examination receive a second induction including daunorubicin IV on days 1-3 and cytarabine CIVI over 12 hours on days 1-5.

CONSOLIDATION: Patients receive cytarabine IV over 3 hours on days 1-5. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

ARM 2: INDUCTION: Patients receive uproleselan IV QD on day 1 and then every 12 hours on days 2-10. Patients also receive daunorubicin IV on days 2-4 and cytrarabine CIVI over 168 hours on days 2-8 over 168 hours. Patients with residual disease indicated by bone marrow examination receive a second induction including uprleselan IV QD on day 1 and then every 12 hours on days 2-8, daunorubicin IV on days 2-3, and cytarabine CIVI over 120 hours on days 2-6.

CONSOLIDATION: Patients who achieve a CR or CRi receive uproleselan IV QD on day 1 and every 12 hours on days 2-8 and cytarabine IV over 3 hours on days 2-6. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 1 year, every 3 months in year 2, and then every 6 months for up to 5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE
  • 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
    Given IV
    Other Names:
    • Daunomycin
    • Daunorrubicina
    • DNR
    • Leukaemomycin C
    • Rubidomycin
    • Rubomycin C
  • Drug: Uproleselan
    Given IV
    Other Name: GMI-1271
Study Arms  ICMJE
  • Active Comparator: Arm I (daunorubicin, cytarabine)

    INDUCTION: Patients receive daunorubicin IV on days 1-3 and cytarabine via CIVI over 168 hours on days 1-7. Patients with residual disease indicated by bone marrow examination receive a second induction including daunorubicin IV on days 1-3 and cytarabine CIVI over 12 hours on days 1-5.

    CONSOLIDATION: Patients receive cytarabine IV over 3 hours on days 1-5. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

    Interventions:
    • Drug: Cytarabine
    • Drug: Daunorubicin
  • Experimental: Arm II (uproleselan, daunorubicin, cytarabine)

    INDUCTION: Patients receive uproleselan IV QD on day 1 and then every 12 hours on days 2-10. Patients also receive daunorubicin IV on days 2-4 and cytrarabine CIVI over 168 hours on days 2-8 over 168 hours. Patients with residual disease indicated by bone marrow examination receive a second induction including uprleselan IV QD on day 1 and then every 12 hours on days 2-8, daunorubicin IV on days 2-3, and cytarabine CIVI over 120 hours on days 2-6.

    CONSOLIDATION: Patients who achieve a CR or CRi receive uproleselan IV QD on day 1 and every 12 hours on days 2-8 and cytarabine IV over 3 hours on days 2-6. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

    Interventions:
    • Drug: Cytarabine
    • Drug: Daunorubicin
    • Drug: Uproleselan
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: April 30, 2019)
670
Original Estimated Enrollment  ICMJE
 (submitted: October 8, 2018)
932
Estimated Study Completion Date  ICMJE December 1, 2025
Estimated Primary Completion Date December 1, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of acute myeloid leukemia (AML) based on 2017 World Health Organization (WHO) criteria excluding acute promyelocytic leukemia with PML-RARA.

    • Note: Patients with myeloid sarcoma without bone marrow involvement, acute leukemia of ambiguous lineage or blast transformation of chronic myelogenous leukemia (CML) are not eligible.
  • No activating mutation in the Fms-like tyrosine kinase-3 (FLT3) defined as a ratio of mutant to wild-type allele >= 0.05 by capillary electrophoresis or a variant allele fraction of >= 5% by next generation sequencing from either bone marrow or peripheral blood.
  • No evidence of CNS involvement of AML.
  • No prior chemotherapy for myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN) or AML including hypomethylating agents (e.g. azacitidine and decitabine), ruxolitinib or lenalidomide with the following exceptions:

    • Emergency leukapheresis.
    • Hydroxyurea.
    • Growth factor/cytokine support.
    • All-trans retinoic acid (ATRA).
    • Single dose of intrathecal cytarabine and/or methotrexate for patients undergoing lumbar puncture to evaluate for CNS involvement.
  • Total bilirubin =< 3 x upper limit of normal (ULN)
  • Creatinine < 3 x upper limit of normal (ULN) OR creatinine clearance >= 30 mL/min/1.73m^2
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 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 NCT03701308
Other Study ID Numbers  ICMJE NCI-2018-02130
NCI-2018-02130 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
A041701 ( Other Identifier: Alliance for Clinical Trials in Oncology )
A041701 ( Other Identifier: CTEP )
U10CA180821 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
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: Yes
Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
URL: https://grants.nih.gov/policy/sharing.htm
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Geoffrey L Uy Alliance for Clinical Trials in Oncology
PRS Account National Cancer Institute (NCI)
Verification Date May 2021

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