Acute Myeloid Leukemia
Conditions
Brief summary
This is a standard phase 2 study powered to demonstrate improvement in the 100 day leukemia free survival to 30% from \<10% expected with the use of reduced intensity haplo-HCT in this extremely high-risk patient cohort (based on the institutional experience using non-myeloablative / reduced intensity conditioning in a similar patient cohort). A formal safety evaluation will be done after every 6th patient enrolled and the trial will be stopped if noted to have unusually higher engraftment failure (acute GVHD rates (\>60% any grades or \>30% grade III/IV or ≥ 50% severe cGVHD) or engraftment failure rates (≥15%).
Interventions
PROCEDUREGraft cell infusion
-Day 0
DRUGTacrolimus
-GVHD prophylaxis
DRUGMycophenolate mofetil
-GVHD prophylaxis
DRUGG-CSF
-Continue until neutrophil engraftment as per institutional guidelines
PROCEDURECIML NK cell infusion
-Day +7
DRUGALT-803
-Start approximately 4 hours after CIML NK cell infusion
PROCEDURELeukapheresis
-Day +6
Sponsors
Washington University School of Medicine
National Institutes of Health (NIH)
The V Foundation for Cancer Research
National Cancer Institute (NCI)
ImmunityBio, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Recipient Inclusion Criteria: * Refractory AML without complete remission (CR) after 2 or more cycles of induction therapy (primary induction failure), or AML relapsed after obtaining a CR and failed one or more cycles of re-induction therapy. Standard dose 10-day decitabine (20 mg/m2 daily IV x 10 days) or 7-day azacitidine (75-100 mg/m2 daily SC/IV x 7 days) will be considered as one cycle of induction therapy. * At least 18 years of age * Available HLA-haploidentical donor that meets the criteria in the protocol * Patients with known CNS involvement with AML are eligible provided that they have been treated and CSF is clear for at least 2 weeks prior to enrollment into the study. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment. * Karnofsky performance status \> 60 % * Adequate organ function as defined below: * Total bilirubin \< 2 mg/dl * AST(SGOT)/ALT(SGPT) \< 3.0 x IULN * Creatinine within normal institutional limits OR creatinine clearance \> 60 mL/min/1.73 m2 by Cockcroft-Gault Formula * Oxygen saturation ≥90% on room air and adjusted DLCO of at least 40% * Ejection fraction ≥40% * Able to be off of corticosteroids (10 mg or less of prednisone or equivalent doses of other systemic steroids are allowed) and any other immune suppressive medications beginning on Day -3 * Women of childbearing potential must have a negative pregnancy test within 28 days prior to study registration. Female and male patients (along with their female partners) must agree to use two forms of acceptable contraception, including one barrier method, during participation in the study and throughout the DLT evaluation period. * Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable). Recipient
Exclusion criteria
* Relapsed after allogeneic transplantation. * Circulating blast count \>30,000/uL by morphology or flow cytometry (cyto-reductive therapies including leukapheresis or hydroxyurea are allowed). * Uncontrolled bacterial or viral infections, or known HIV, Hepatitis B or C infection. * Presence of donor specific antibodies (DSA) with Mean Fluorescence Intensity (MFI) of \>5000 as assessed by the single antigen bead assay, \< 6 weeks prior to starting transplant conditioning * Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive of acute ischemia or active conduction system abnormalities. * New progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that have not been evaluated with bronchoscopy. Infiltrates attributed to infection must be stable/ improving after 1 week of appropriate therapy (4 weeks for presumed or proven fungal infections) * Known hypersensitivity to one or more of the study agents * Received any investigational drugs within the 14 days prior to the first day of transplant conditioning * Pregnant and/or breastfeeding Donor Inclusion Criteria: * Related donor (sibling, offspring, or offspring of sibling) * At least 18 years of age * HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A\&B locus. * In general good health, and medically able to tolerate leukapheresis required for harvesting the NK cells for this study. * Ability to understand and willingness to sign an IRB approved written informed consent document Donor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimate of Leukemia-free Survival Rate (LFS) | 1 year post transplantation | -LFS is defined as the time from achievement of complete remission (CR) to the time of relapse, death in remission, or last follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimate of Leukemia-free Survival Rate (LFS) | 3 months post transplantation | -LFS is defined as the time from achievement of CR to the time of relapse, death in remission, or last follow-up. |
| Kaplan-Meier Estimate of Overall Survival (OS) | 1 year post transplantation | -OS is defined as the time from the date of Day 0 until death from any cause. |
| Number of Recipients With Relapse Who Are Found to be CR (Complete Remission) | Day 28 post transplantation | -CR: Morphologically leukemia free state (i.e. bone marrow with \<5% blasts by morphologic criteria and no blasts with Auer rods, no evidence of extramedullary leukemia) and absolute neutrophil count ≥1000 /μL and platelets ≥100,000 /μL. Patient must be independent of transfusions. |
| Complete Remission (CR) Rate | Day 28 post transplantation | CR: Morphologically leukemia free state (i.e. bone marrow with \<5% blasts by morphologic criteria and no blasts with Auer rods, no evidence of extramedullary leukemia) and absolute neutrophil count ≥1000 /μL and platelets ≥100,000 /μL. Patient must be independent of transfusions |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAmanda Cashen, M.D.
Washington University School of Medicine
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 39.9 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 1 Participants |
| Race (NIH/OMB) White | 55 Participants |
| Region of Enrollment United States | 60 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 27 / 29 | 0 / 0 |
| other Total, other adverse events | 29 / 29 | 0 / 0 |
| serious Total, serious adverse events | 10 / 29 | 0 / 0 |
Outcome results
None listed