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AML Therapy With Irradiated Allogeneic Cells

Primary Purpose

Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a)

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
fludarabine phosphate
cytarabine
donor lymphocytes
laboratory biomarker analysis
G-CSF
Sponsored by
Rutgers, The State University of New Jersey
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Acute Megakaryoblastic Leukemia (M7)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 10^3/mm^3
  • 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

Sites / Locations

  • Rutgers Cancer Institute of New Jersey

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Standard chemotherapy followed by allogenic therapy

Arm Description

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.

Outcomes

Primary Outcome Measures

Adverse Events Related to Experimental Therapy
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.
Response Rate, Determined by Allogeneic Cell Therapy-related Mortality
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.
Response Rate, Determined by Duration of Complete Remission
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

Progression Free Survival Probability for CR
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.

Full Information

First Posted
April 2, 2014
Last Updated
August 20, 2021
Sponsor
Rutgers, The State University of New Jersey
Collaborators
National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey
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1. Study Identification

Unique Protocol Identification Number
NCT02105116
Brief Title
AML Therapy With Irradiated Allogeneic Cells
Official Title
AML Therapy With Irradiated Allogeneic Cells
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
No patients were eligible to receive the experimental component of the protocol therapy.
Study Start Date
February 2014 (undefined)
Primary Completion Date
December 16, 2015 (Actual)
Study Completion Date
December 16, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rutgers, The State University of New Jersey
Collaborators
National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey

4. Oversight

Data Monitoring Committee
No

5. 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: I. 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. II. 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: I. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Myelomonocytic Leukemia (M4), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Recurrent Adult Acute Myeloid Leukemia, Untreated Adult Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard chemotherapy followed by allogenic therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Other Intervention Name(s)
2-F-ara-AMP, Beneflur, Fludara
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cytarabine
Other Intervention Name(s)
ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
donor lymphocytes
Intervention Description
Undergo infusion of donor lymphocytes
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
G-CSF
Other Intervention Name(s)
Filgrastim, Neupogen®
Intervention Description
Given IV
Primary Outcome Measure Information:
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
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
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
Secondary Outcome Measure Information:
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 10^3/mm^3 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roger Strair, MD, PhD
Organizational Affiliation
Rutgers Cancer Institute of New Jersey
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States

12. IPD Sharing Statement

Learn more about this trial

AML Therapy With Irradiated Allogeneic Cells

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