AML Therapy With Irradiated Allogeneic Cells

NCT ID: NCT02105116

Last Updated: 2021-08-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2015-12-16

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

fludarabine phosphate

Intervention Type: DRUG

Given IV

cytarabine

Intervention Type: DRUG

Given IV

donor lymphocytes

Intervention Type: BIOLOGICAL

Undergo infusion of donor lymphocytes

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

G-CSF

Intervention Type: DRUG

Given IV

Interventions

fludarabine phosphate

Given IV

Intervention Type: DRUG

cytarabine

Given IV

Intervention Type: DRUG

donor lymphocytes

Undergo infusion of donor lymphocytes

Intervention Type: BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

G-CSF

Given IV

Intervention Type: DRUG

Other Intervention Names

2-F-ara-AMP; Beneflur; Fludara; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside; Filgrastim; Neupogen®

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)
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Rutgers Cancer Institute of New Jersey

OTHER

Sponsor Role: collaborator

Rutgers, The State University of New Jersey

OTHER

Sponsor Role: lead

Responsible Party

Roger Strair, MD, PhD

Professor of Medicine, RWJMS

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Roger Strair, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Rutgers Cancer Institute of New Jersey

Locations

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Countries

United States

Other Identifiers

NCI-2013-02408

Identifier Type: REGISTRY

Identifier Source: secondary_id

Pro2013002693

Identifier Type: OTHER

Identifier Source: secondary_id

021208

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA072720

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro2013002693

Identifier Type: -

Identifier Source: org_study_id