Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS)
Conditions
Brief summary
This is a single-arm, multi-center Phase II trial using IL-15 super-agonist complex (N-803 formerly known as Alt-803) maintenance after allogeneic hematopoietic cell transplant (alloHCT) for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS).
Interventions
DRUGN-803
N-803 at 6 mcg/kg SQ Day 1 of a 4 week (28 day) cycle with ± 1 week window Continue N-803 every 4 weeks for 10 doses or until relapse, unacceptable toxicity, or patient refusal, whichever comes earlier.
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
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) for whom an allogeneic hematopoietic stem cell transplant using a reduced intensity conditioning is planned or has been performed and patient is prior to day 60 post-transplant. 2. Able to begin study treatment between day +42 and day +60 after the transplant and meets the following transplant related requirements: * Sustained neutrophil (ANC \> 1000/mcL) and platelet (\> 30,000/mcL) engraftment * \>50% donor myeloid and lymphoid chimerism blood or bone marrow on most recent bone marrow (BM) evaluation * No evidence of recurrent disease on most recent bone marrow evaluation (day 21 or 28 post-transplant is acceptable) * No morphologic evidence of relapse (\< 5% bone marrow blasts) on most recent BM evaluation (Day 21 or 28 post-transplant is acceptable) * Being followed in the outpatient setting (not an inpatient) * No plan of giving other anti-cancer treatment directed at diseases under study (i.e. maintenance therapy \[e.g. sorafenib for FLT3m+ AML or hypomethylating therapy\], additional therapy for MRD) 3. If acute GVHD is present it must be clinically improving on topical steroids and/or on low dose systemic steroids (≤ 0.3 mg/kg/day prednisone) and with clinical stability for at least 1 week prior to determination of eligibility. GVHD prophylaxis will be continued per individual institutional standard practice 4. One of the following donor graft sources used for the transplant: * Group 1: sibling donor * Group 2: haploidentical donor \[with post-transplant cyclophosphamide\] * Group 3: unrelated donor * Group 4: unrelated umbilical cord blood 5. Karnofsky performance status ≥ 70% 6. Adequate organ function within 14 days of study enrollment defined as: * Renal: serum creatinine: ≤ 2.0 mg/dL * Hepatic: SGOT ≤ 3 x upper limit of institutional normal (ULN) 7. Sexually active females of child-bearing potential and males with partners of child bearing potential must agree to use effective contraception during therapy and for 4 months after completion of therapy. 8. Voluntary written consent prior to the performance of any research related procedures
Exclusion criteria
1. Prior N-803 (previously known as ALT-803) 2. Pregnant or breastfeeding - N-803 is an investigational agent. Women of child bearing potential must have a negative pregnancy test at screening. 3. Class II or greater New York Heart Association Functional Classification criteria or serious cardiac arrhythmias likely to increase the risk of cardiac complications of cytokine therapy (e.g. ventricular tachycardia, frequent ventricular ectopy, or supraventricular tachyarrhythmia requiring chronic therapy) 4. Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval \> 500 milliseconds) 5. Active uncontrolled bacterial, fungal, or viral infections - all prior infections must have resolved following optimal therapy and must be afebrile for at least 24 hours at time of enrollment. 6. Active autoimmune disease requiring immunosuppressive therapy (GVHD prophylaxis is permitted per institutional practice) 7. History of severe asthma and currently on chronic medications (mild asthma requiring inhaled steroids only is eligible) 8. Received any investigational agent within the 14 days before the start of study treatment (1st dose of N-803)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Relapse | 24 months | Efficacy of N-803 as measured by the cumulative incidence of relapse between the 1st dose of N-803 and 2 years after a reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplant (alloHCT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Acute Graft-versus-host Disease | Day 100 | Incidence of grade 2-4 and grade 3-4 acute graft-versus-host-disease (GVHD) |
| Chronic GVHD | 1 year | Incidence of acute graft-versus-host disease |
| Minimal Residual Disease (MRD) | 1 year | Incidence of minimal residual disease (MRD) post-transplant |
| Incidence of Adverse Events | 12 months | Frequency of all adverse |
| Non-Relapse Mortality | 1 year | Incidence of non-relapse mortality |
| Relapse | 2 Years | Incidence of relapse at 2 years after alloHCT stratified by number of doses of N-803 (1-3 or 4-10) |
| Overall Survival | 1 year post transplant | Incidence of overall survival at one year |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| N-803 N-803: N-803 at 6 mcg/kg SQ Day 1 of a 4 week (28 day) cycle with ± 1 week window Continue N-803 every 4 weeks for 10 doses or until relapse, unacceptable toxicity, or patient refusal, whichever comes earlier. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | N-803 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 19 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 7 / 20 |
Outcome results
Primary
Incidence of Relapse
Efficacy of N-803 as measured by the cumulative incidence of relapse between the 1st dose of N-803 and 2 years after a reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplant (alloHCT)
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| N-803 | Incidence of Relapse | 30 Percentage of participants |
Secondary
Chronic GVHD
Incidence of acute graft-versus-host disease
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| N-803 | Chronic GVHD | 15 Percentage of participants |
Secondary
Incidence of Acute Graft-versus-host Disease
Incidence of grade 2-4 and grade 3-4 acute graft-versus-host-disease (GVHD)
Time frame: Day 100
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| N-803 | Incidence of Acute Graft-versus-host Disease | Grade 2-4 GVHD | 10 Percentage of participants |
| N-803 | Incidence of Acute Graft-versus-host Disease | Grade 3-4 GVHD | 0 Percentage of participants |
Secondary
Incidence of Acute Graft-versus-host Disease
Incidence of grade 2-4 and grade 3-4 acute graft-versus-host-disease (GVHD)
Time frame: Day 180
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| N-803 | Incidence of Acute Graft-versus-host Disease | Grade 2-4 GVHD | 15 Percentage of participants |
| N-803 | Incidence of Acute Graft-versus-host Disease | Grade 3-4 GVHD | 5 Percentage of participants |
Secondary
Incidence of Adverse Events
Frequency of all adverse
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| N-803 | Incidence of Adverse Events | 567 Count of events |
Secondary
Minimal Residual Disease (MRD)
Incidence of minimal residual disease (MRD) post-transplant
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| N-803 | Minimal Residual Disease (MRD) | 26 Percentage of participants |
Secondary
Non-Relapse Mortality
Incidence of non-relapse mortality
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| N-803 | Non-Relapse Mortality | 5 Percentage of participants |
Secondary
Overall Survival
Incidence of overall survival at one year
Time frame: 1 year post transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| N-803 | Overall Survival | 85 Percentage of participants |
Secondary
Relapse
Incidence of relapse at 2 years after alloHCT stratified by number of doses of N-803 (1-3 or 4-10)
Time frame: 2 Years
Population: Intent is to compare the percentage of participants with relapse stratified according the number of doses of N-803 that were administered.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| N-803 | Relapse | 1-3 doses of N-803 | 62 Percentage of participants |
| N-803 | Relapse | 4-10 doses of N-803 | 17 Percentage of participants |