AML Therapy With Irradiated Allogeneic Cells

Sponsor
Rutgers, The State University of New Jersey (Other)
Overall Status
Terminated
CT.gov ID
NCT02105116
Collaborator
National Cancer Institute (NCI) (NIH), Rutgers Cancer Institute of New Jersey (Other)
6
1
1
22.4
0.3

Study Details

Study Description

Brief Summary

This pilot clinical trial studies if cells donated by a close genetic relative can help maintain acute myeloid leukemia (AML) complete remission (CR). Eligible patients will receive a standard induction chemotherapy. If a complete remission results they will receive irradiated allogeneic cells from a HLA haploidentical relative. Only patients who obtain a CR after the standard induction chemotherapy are eligible for the experimental therapy (irradiated haploidentical cells).

Detailed Description

PRIMARY OBJECTIVES:
  1. Toxicity of haploidentical allogeneic cellular therapy in patients in complete remission (CR) (or CR with incomplete platelet recovery [CRp]) after induction chemotherapy with fludarabine (fludarabine phosphate)-cytarabine.

  2. Efficacy of haploidentical allogeneic cellular therapy in patients in CR (or CRp) after induction chemotherapy with fludarabine-cytarabine (remission rates at 6, 12, 18, 24 months).

SECONDARY OBJECTIVES:
  1. Immunologic parameters before and after haploidentical therapy: host anti-leukemia T cells; host regulatory T cells.
OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive fludarabine phosphate intravenously (IV) over 1 hour once daily (QD) for 5 days and cytarabine IV over 4 hours for 5 days. Treatment may continue for 1 or 2 courses at the discretion of the treating physician.

ALLOGENEIC CELLULAR THERAPY: Patients undergo irradiated donor lymphocyte infusion (DLI) of 3 x 10^8 cluster of differentiation (CD)3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 2 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
6 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
AML Therapy With Irradiated Allogeneic Cells
Study Start Date :
Feb 1, 2014
Actual Primary Completion Date :
Dec 16, 2015
Actual Study Completion Date :
Dec 16, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Standard chemotherapy followed by allogenic therapy

INDUCTION CHEMOTHERAPY: Patients receive standard induction chemotherapy with fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. If the patient enters a complete remission they are eligible for ALLOGENEIC CELLULAR THERAPY: Patients eligible for the experimental therapy undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity.

Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
  • Drug: cytarabine
    Given IV
    Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
  • Biological: donor lymphocytes
    Undergo infusion of donor lymphocytes

    Other: laboratory biomarker analysis
    Correlative studies

    Drug: G-CSF
    Given IV
    Other Names:
  • Filgrastim
  • Neupogen┬«
  • Outcome Measures

    Primary Outcome Measures

    1. Adverse Events Related to Experimental Therapy [Up to 2 years]

      Patients will be observed for incidence of adverse events related to experimental therapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Of the 6 patients enrolled, all were ineligible to enter the experimental treatment phase of the study because of failure to reach complete remission. None of the enrolled patients received experimental therapy (allogeneic donor lymphocyte therapy). The one death occurred while receiving standard therapy prior to eligibility for experimental allogeneic therapy. The remained of patients were ineligible for experimental therapy because they did not obtain a complete remission after standard induction chemotherapy.

    2. Response Rate, Determined by Allogeneic Cell Therapy-related Mortality [Up to 2 years]

      Patients' response rate will be determined by allogeneic cell therapy-related mortality. Of the 6 patients enrolled, all were ineligible to enter the experimental treatment phase of the study for failure to reach complete remission. Hence no outcomes are available.

    3. Response Rate, Determined by Duration of Complete Remission [Up to 2 years]

      Patients will be scored as being in continuous remission at 2 years or having relapsed sooner. Of the 6 patients enrolled, all were ineligible to enter the treatment phase of the study for failure to reach complete remission for allogenic treatment.

    Secondary Outcome Measures

    1. Progression Free Survival Probability for CR [At 2 years]

      Calculated using Kaplan-Meier estimation method. Corresponding 95% confidence interval will be provided. Of the 6 patients enrolled, all were ineligible to enter the experimental treatment phase of the study for failure to reach complete remission. Hence no outcomes are available.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically proven non-M3 AML:

    • Refractory/relapsed AML OR

    • Initial diagnosis of AML in patient >= 60 years old

    • Total bilirubin =< 1.5 times upper limit of normal (ULN) institutional limits (unless Gilbert's disease)

    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional ULN

    • Cardiac left ventricular ejection fraction (LVEF) >= 35%

    • Serum creatinine =< 1.5 mg/dl

    • Any organ dysfunction thought to be secondary to disease will be considered separately and the patient will be included at the investigators discretion

    • Patients must give informed consent

    • Eastern Cooperative Oncology Group (ECOG) performance status =< 3

    • Must have a potential haploidentical donor (parent, sibling, child)

    • A patient is eligible for second enrollment (allo-cellular therapy) if all of the following inclusion criteria are met:

    • Patient must have documented CR or CRp after 1 or 2 cycles of fludarabine + cytarabine

    • Patient must not be a candidate for an allo-hematopoietic stem cell transplant (HSCT)

    • Patient must have a partially (>= 3/6 class I antigen) human leukocyte antigen (HLA)-matched (by serology or low resolution deoxyribonucleic acid [DNA] testing) relative able to serve as a donor

    • Patients must not have active uncontrolled infections, other medical or psychological/social conditions that might increase the likelihood of patient adverse effects or poor outcomes

    • Total bilirubin < 1.5 times upper limit of normal (ULN) institutional limits (unless Gilbert's disease)

    • AST(SGOT)/ALT(SGPT) =< 2.5 X institutional ULN

    • Serum creatinine < 2.0 mg/dl

    • ECOG performance status =< 2

    • DONOR: donor must be related to patient and be partially (>= 3/6 antigen) HLA-matched

    • DONOR: donor must meet all New Brunswick Affiliated Hospitals (NBAH) requirements for hematopoietic stem cell donation, including:

    • DONOR: age >= 18 years old

    • DONOR: white blood cells (WBC) 4.0-10.0 x 103/mm3

    • DONOR: platelet count 150,000 to 440,000/mm^3

    • DONOR: hemoglobin/hematocrit; 12.5-18 g/dl, 38 to 54%

    • DONOR: not pregnant or lactating

    • DONOR: not human immunodeficiency virus (HIV)-1, HIV-2, hepatitis C virus (HCV), hepatitis B core or human T-lymphotropic virus (HTLV)-I/II seropositive; hepatitis B surface antigen (HB S ag) (-); meet other infectious disease screening criteria utilized by NBAH Blood Center

    • DONOR: no uncontrolled infections, other medical or psychological/social conditions, or medications that might increase the likelihood of patient or donor adverse effects or poor outcomes

    • DONOR: meet other blood bank criteria for blood product donation (as determined by NBAH Blood Center screening history and laboratory studies)

    Exclusion Criteria:
    • History of current or prior medical problems that the investigator feels will prevent administration of therapy or assessment of response due to excess toxicity

    • Patients with known active central nervous system (CNS) leukemia will be excluded from this clinical study

    • Known HIV-positive patients are excluded from the study

    • Patients may not be pregnant or breast feeding

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08903

    Sponsors and Collaborators

    • Rutgers, The State University of New Jersey
    • National Cancer Institute (NCI)
    • Rutgers Cancer Institute of New Jersey

    Investigators

    • Principal Investigator: Roger Strair, MD, PhD, Rutgers Cancer Institute of New Jersey

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Roger Strair, MD, PhD, Professor of Medicine, RWJMS, Rutgers Cancer Institute of New Jersey
    ClinicalTrials.gov Identifier:
    NCT02105116
    Other Study ID Numbers:
    • Pro2013002693
    • NCI-2013-02408
    • Pro2013002693
    • 021208
    • P30CA072720
    First Posted:
    Apr 7, 2014
    Last Update Posted:
    Aug 24, 2021
    Last Verified:
    Aug 1, 2021

    Study Results

    Participant Flow

    Recruitment Details Subjects were recruited through the Rutgers Cancer Institute of New Jersey. The study was open to accrual on 02/17/2014 and was closed to accrual on 08/25/2015. The study was terminated on 12/16/2015.
    Pre-assignment Detail We are reporting results on 6 eligible patients. One patient was deemed ineligible.
    Arm/Group Title Treatment (Combination Chemotherapy, DLI)
    Arm/Group Description INDUCTION CHEMOTHERAPY: Patients receive fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. ALLOGENEIC CELLULAR THERAPY: Patients undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity. fludarabine phosphate: Given IV cytarabine: Given IV donor lymphocytes: Undergo infusion of donor lymphocytes laboratory biomarker analysis: Correlative studies G-CSF: Given IV
    Period Title: Overall Study
    STARTED 6
    COMPLETED 0
    NOT COMPLETED 6

    Baseline Characteristics

    Arm/Group Title Treatment (Combination Chemotherapy, DLI)
    Arm/Group Description INDUCTION CHEMOTHERAPY: Patients receive fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. ALLOGENEIC CELLULAR THERAPY: Patients undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity. fludarabine phosphate: Given IV cytarabine: Given IV donor lymphocytes: Undergo infusion of donor lymphocytes laboratory biomarker analysis: Correlative studies G-CSF: Given IV
    Overall Participants 6
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    1
    16.7%
    >=65 years
    5
    83.3%
    Sex: Female, Male (Count of Participants)
    Female
    1
    16.7%
    Male
    5
    83.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    16.7%
    Not Hispanic or Latino
    5
    83.3%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    1
    16.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    2
    33.3%
    White
    3
    50%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    6
    100%

    Outcome Measures

    1. Primary Outcome
    Title Adverse Events Related to Experimental Therapy
    Description Patients will be observed for incidence of adverse events related to experimental therapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Of the 6 patients enrolled, all were ineligible to enter the experimental treatment phase of the study because of failure to reach complete remission. None of the enrolled patients received experimental therapy (allogeneic donor lymphocyte therapy). The one death occurred while receiving standard therapy prior to eligibility for experimental allogeneic therapy. The remained of patients were ineligible for experimental therapy because they did not obtain a complete remission after standard induction chemotherapy.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Combination Chemotherapy, DLI)
    Arm/Group Description INDUCTION CHEMOTHERAPY: Patients receive fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. ALLOGENEIC CELLULAR THERAPY: Patients undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity. fludarabine phosphate: Given IV cytarabine: Given IV donor lymphocytes: Undergo infusion of donor lymphocytes laboratory biomarker analysis: Correlative studies G-CSF: Given IV
    Measure Participants 0
    2. Primary Outcome
    Title Response Rate, Determined by Allogeneic Cell Therapy-related Mortality
    Description Patients' response rate will be determined by allogeneic cell therapy-related mortality. Of the 6 patients enrolled, all were ineligible to enter the experimental treatment phase of the study for failure to reach complete remission. Hence no outcomes are available.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Combination Chemotherapy, DLI)
    Arm/Group Description INDUCTION CHEMOTHERAPY: Patients receive fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. ALLOGENEIC CELLULAR THERAPY: Patients undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity. fludarabine phosphate: Given IV cytarabine: Given IV donor lymphocytes: Undergo infusion of donor lymphocytes laboratory biomarker analysis: Correlative studies G-CSF: Given IV
    Measure Participants 0
    3. Primary Outcome
    Title Response Rate, Determined by Duration of Complete Remission
    Description Patients will be scored as being in continuous remission at 2 years or having relapsed sooner. Of the 6 patients enrolled, all were ineligible to enter the treatment phase of the study for failure to reach complete remission for allogenic treatment.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Combination Chemotherapy, DLI)
    Arm/Group Description INDUCTION CHEMOTHERAPY: Patients receive fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. ALLOGENEIC CELLULAR THERAPY: Patients undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity. fludarabine phosphate: Given IV cytarabine: Given IV donor lymphocytes: Undergo infusion of donor lymphocytes laboratory biomarker analysis: Correlative studies G-CSF: Given IV
    Measure Participants 0
    4. Secondary Outcome
    Title Progression Free Survival Probability for CR
    Description Calculated using Kaplan-Meier estimation method. Corresponding 95% confidence interval will be provided. Of the 6 patients enrolled, all were ineligible to enter the experimental treatment phase of the study for failure to reach complete remission. Hence no outcomes are available.
    Time Frame At 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Combination Chemotherapy, DLI)
    Arm/Group Description INDUCTION CHEMOTHERAPY: Patients receive fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. ALLOGENEIC CELLULAR THERAPY: Patients undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity. fludarabine phosphate: Given IV cytarabine: Given IV donor lymphocytes: Undergo infusion of donor lymphocytes laboratory biomarker analysis: Correlative studies G-CSF: Given IV
    Measure Participants 0

    Adverse Events

    Time Frame Adverse events were collected over a period of 340 days per patient.
    Adverse Event Reporting Description
    Arm/Group Title Treatment (Combination Chemotherapy, DLI)
    Arm/Group Description INDUCTION CHEMOTHERAPY: Patients receive fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. ALLOGENEIC CELLULAR THERAPY: Patients undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity. fludarabine phosphate: Given IV cytarabine: Given IV donor lymphocytes: Undergo infusion of donor lymphocytes laboratory biomarker analysis: Correlative studies G-CSF: Given IV
    All Cause Mortality
    Treatment (Combination Chemotherapy, DLI)
    Affected / at Risk (%) # Events
    Total 1/6 (16.7%)
    Serious Adverse Events
    Treatment (Combination Chemotherapy, DLI)
    Affected / at Risk (%) # Events
    Total 0/6 (0%)
    Other (Not Including Serious) Adverse Events
    Treatment (Combination Chemotherapy, DLI)
    Affected / at Risk (%) # Events
    Total 0/6 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Roger Strair, MD, PhD
    Organization Rutgers Cancer Institute of New Jersey
    Phone 732-235-7298
    Email strairrk@cinj.rutgers.edu
    Responsible Party:
    Roger Strair, MD, PhD, Professor of Medicine, RWJMS, Rutgers Cancer Institute of New Jersey
    ClinicalTrials.gov Identifier:
    NCT02105116
    Other Study ID Numbers:
    • Pro2013002693
    • NCI-2013-02408
    • Pro2013002693
    • 021208
    • P30CA072720
    First Posted:
    Apr 7, 2014
    Last Update Posted:
    Aug 24, 2021
    Last Verified:
    Aug 1, 2021