Leukemia
Conditions
Keywords
recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, secondary acute myeloid leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22)
Brief summary
RATIONALE: Giving chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells and natural killer (NK) cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. PURPOSE: This clinical trial is studying how well a peripheral stem cell transplant using NK cells from a donor works in treating patients with relapsed acute myeloid leukemia.
Detailed description
OBJECTIVES: Primary * Evaluate the in vivo expansion of natural killer (NK) cells 14 days after treatment with allogeneic NK cell-enriched peripheral blood stem cell transplantation in patients with relapsed acute myeloid leukemia. Secondary * Determine the response rate, in terms of complete remission, in patients treated with this regimen. * Correlate complete remission rate with NK cell expansion, interleukin-15 levels, and donor/recipient killer immunoglobulin receptor (KIR) ligand matching status in patients treated with this regimen. * Determine the overall and progression-free survival of patients treated with this regimen. * Determine the toxicity of this regimen in these patients. OUTLINE: This is an open-label study. * Induction therapy: Patients receive fludarabine IV on days -6 to -2 and cyclophosphamide IV on day -5 or on days -5 and -4. * Allogeneic natural killer (NK) cell-enriched peripheral blood stem cell transplantation: Patients receive allogeneic NK cell-enriched peripheral blood stem cells IV over 15-60 minutes on day 0. Patients also receive interleukin-2 subcutaneously beginning on day 0 and continuing 3 times a week for up to 2 weeks. After completion of study treatment, patients are followed periodically for 3 months.
Interventions
BIOLOGICALaldesleukin
10 million units three times a week for a total of 6 doses. For any subject less than 45 kilograms the IL-2 will be given at 5 million units per meter squared three times weekly for a total of 6 doses
BIOLOGICALtherapeutic allogeneic lymphocytes
Cells infused per kg. 1.5-8.0 x 10\^7/kg Total cells infused(for 70 kg. adult) 1.05 - 5.6 x 10\^9
DRUGcyclophosphamide
Days -5 and -4: 60 mg/kg
DRUGfludarabine phosphate
Days -5 through -2: 25 mg/m\^2
PROCEDUREin vitro treated peripheral blood stem cell transplantation
Day 0 infuse natural killer cells
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of acute myeloid leukemia (AML) meeting 1 of the following criteria: * Primary refractory disease (no complete response \[CR\] after ≥ 2 induction therapies) * Relapsed disease not in CR after ≥ 1 course of standard reinduction therapy * Secondary AML from myelodysplastic syndromes * Disease relapsed ≥ 2 months after transplant and no option of donor lymphocyte infusions (e.g., recipients of autologous or umbilical cord blood transplants) * Chronic myelogenous leukemia with myeloid blast crisis not in second chronic phase after at least one cycle of standard chemotherapy and imatinib * Over 60 years of age with relapse within 6 months after completion of last chemotherapy * Over 60 years of age with blast count \< 30% within 10 days before study entry * Related HLA-haploidentical natural killer cell donor available * No severe organ damage (by clinical or laboratory assessment) * Performance status 50-100% * No evidence of active infection on chest X-ray * No active fungal infection
Exclusion criteria
* Active central nervous system (CNS) leukemia * Pleural effusions large enough to be detectable by chest x-ray * Pregnant or nursing (positive pregnancy test) * Fertile patients must use effective contraception * Less than 60 days since prior transplant * Less than 3 days since prior prednisone * Less than 3 days since other prior immunosuppressive medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Natural Killer (NK) Cell Expansion | Study Day 14 | Evaluation of expansion of donor allogeneic natural killer (NK) cells at day 14 following infusion (\>100 donor-derived NK cells per uL of patient blood detectable at day +14). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Complete Remission | Day 28-35 | Clinical response is determined by achievement of a complete remission (CR) as judged by morphological criteria (\< 1% blasts in bone marrow with neutrophil recovery). |
| Median Time to Disease Relapse (Months) | From 1st Day of treatment until death or receipt of bone marrow transplant. | Follow-up continued every 3 months after the allogeneic natural killer (NK) cell infusion, unless they were transplanted, relapsed or had progressive disease. Time in months to relapse of disease is calculcated from 1st day of treatment with NK cells. Relapse occurs when leukemia is detected in bone marrow or blood. |
| Overall Survival Time of Patients With Complete Remission | From Day 1 of Treatment until death or patient received bone marrow transplant. | Median number of months patients were alive after NK cell infusion. |
| Number of Patients With Complete Remission and Natural Killer Cell Expansion | Day 14 | Includes patients who had both a complete remission of disease and an expansion of natural killer cells. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients With Relapsed/Refractory Acute Myeloid Leukemia Patients who met study criteria - relapsed or refractory acute myelogenous leukemia - and were enrolled. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not receive adequate NK cells | 1 |
Baseline characteristics
| Characteristic | Patients With Relapsed/Refractory Acute Myeloid Leukemia |
|---|---|
| Age, Categorical <=18 years | 3 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 40 years STANDARD_DEVIATION 18.8 |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 21 |
| serious Total, serious adverse events | 19 / 21 |
Outcome results
Primary
Number of Patients With Natural Killer (NK) Cell Expansion
Evaluation of expansion of donor allogeneic natural killer (NK) cells at day 14 following infusion (\>100 donor-derived NK cells per uL of patient blood detectable at day +14).
Time frame: Study Day 14
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients With Relapsed/Refractory AML - Evaluable Group | Number of Patients With Natural Killer (NK) Cell Expansion | 2 Participants |
Secondary
Median Time to Disease Relapse (Months)
Follow-up continued every 3 months after the allogeneic natural killer (NK) cell infusion, unless they were transplanted, relapsed or had progressive disease. Time in months to relapse of disease is calculcated from 1st day of treatment with NK cells. Relapse occurs when leukemia is detected in bone marrow or blood.
Time frame: From 1st Day of treatment until death or receipt of bone marrow transplant.
Population: Only 2 of 20 patients that received adequate Natural Killer Cells achieved complete remission, and were therefore evaluable for the time to relapse endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients With Relapsed/Refractory AML - Evaluable Group | Median Time to Disease Relapse (Months) | 7.3 Months |
Secondary
Number of Patients With Complete Remission
Clinical response is determined by achievement of a complete remission (CR) as judged by morphological criteria (\< 1% blasts in bone marrow with neutrophil recovery).
Time frame: Day 28-35
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients With Relapsed/Refractory AML - Evaluable Group | Number of Patients With Complete Remission | 2 Participant |
Secondary
Number of Patients With Complete Remission and Natural Killer Cell Expansion
Includes patients who had both a complete remission of disease and an expansion of natural killer cells.
Time frame: Day 14
Population: Unable to evaluate due to low complete remission rate.
Secondary
Overall Survival Time of Patients With Complete Remission
Median number of months patients were alive after NK cell infusion.
Time frame: From Day 1 of Treatment until death or patient received bone marrow transplant.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients With Relapsed/Refractory AML - Evaluable Group | Overall Survival Time of Patients With Complete Remission | 13 Months |