AML Therapy With Irradiated Allogeneic Cells

Not Applicable

Terminated

Conditions: Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myelomonocytic Leukemia (M4)
Adult Pure Erythroid Leukemia (M6b)
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Erythroleukemia (M6a)
Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
Adult Acute Monocytic Leukemia (M5b)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)

Interventions: Drug: fludarabine phosphate
Drug: cytarabine
Biological: donor lymphocytes
Other: laboratory biomarker analysis
Drug: G-CSF

Registration Number: NCT02105116

Lead Sponsor: Rutgers, The State University of New Jersey

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 6

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Standard chemotherapy followed by allogenic therapy	fludarabine phosphate	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.
Standard chemotherapy followed by allogenic therapy	donor lymphocytes	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.
Standard chemotherapy followed by allogenic therapy	laboratory biomarker analysis	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.
Standard chemotherapy followed by allogenic therapy	cytarabine	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.
Standard chemotherapy followed by allogenic therapy	G-CSF	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.

Primary Outcome Measures

Name	Time	Method
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.
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.
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

Name	Time	Method
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.