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
Conditions
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.
Interventions
OTHERlaboratory biomarker analysis
Correlative studies
DRUGG-CSF
Given IV
DRUGfludarabine phosphate
Given IV
DRUGcytarabine
Given IV
BIOLOGICALdonor lymphocytes
Undergo infusion of donor lymphocytes
Sponsors
National Cancer Institute (NCI)
Rutgers Cancer Institute of New Jersey
Rutgers, The State University of New Jersey
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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 details
We are reporting results on 6 eligible patients. One patient was deemed ineligible.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Combination Chemotherapy, DLI) 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 | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | not eligible for step 2 of trial | 5 |
Baseline characteristics
| Characteristic | Treatment (Combination Chemotherapy, DLI) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 6 |
| other Total, other adverse events | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
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.
Time frame: Up to 2 years
Primary
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.
Time frame: Up to 2 years
Primary
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.
Time frame: Up to 2 years
Secondary
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.
Time frame: At 2 years