Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS)
Conditions
Keywords
Acute Myeloid Leukemia (AML), High-Risk Myelodysplastic Syndrome (MDS), hematopoietic cell transplantation, haplo-cord search, matched unrelated donor search
Brief summary
The study seeks to compare time from formal search to hematopoietic cell transplantation (HCT) for patients 18 years and older, randomized between haplo-cord search and matched unrelated donor (MUD) search for patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS)
Detailed description
Primary Objectives To compare time from formal search to hematopoietic cell transplantation (HCT) for patients 18 years and older, randomized between haplo-cord search and matched unrelated donor (MUD) search for patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) Secondary Objectives * To compare the percentage of patients who undergo HCT in each study cohort * To evaluate overall survival from time to randomization by study cohort
Interventions
BIOLOGICALHaplo-Cord Transplant
For conditioning regimens, haplo-identical grafts will be selected by the Miltenyi Device
PROCEDUREMatched Unrelated Donor Transplant
Sponsors
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for Search Phase: 1. Diagnosis of acute myeloid leukemia (AML) or high or very high-risk MDS by international prognostic scoring system revised for whom transplant is recommended 2. 18 years of age or older 3. Subject is likely to be considered for allogeneic transplant in the opinion of the transplant physician (based on age of patient, health, cytogenetics, and/or molecular characteristics). 4. Karnofsky Performance Status (KPS) \>/= 70% at time of enrollment. An exception will be made for those with lower KPS at enrollment with an acute worsening that is likely to resolve in the treating physicians judgment (e.g., reversible infection,trauma, medication reaction, etc) 5. Ability to understand and the willingness to sign a written informed consent document for the Search Phase. 6. Patient willing to consider HCT 7. A preliminary search has identified: 1. An appropriate minimum 4/6 matched umbilical cord unit at intermediate resolution at HLA-A and B, and high resolution at HLA-DRB with a cell dose above 1 x 10(7) TNC/kg for a single umbilical cord blood (UCB) transplant AND 2. At least one potential 8/8 HLA-matched (HLA-A, -B, -C, and -DRB1) unrelated donor with a probability of 70% AND 3. Availability of a potential related haploidentical donor.
Exclusion criteria
for Search Phase: 1. Prior formal search was instituted 2. Diagnosis of acute promyelocytic leukemia (APL) 3. Known HLA matched related donor without contraindications to donate 4. Life expectancy severely limited by concomitant illness or uncontrolled infection Inclusion Criteria for Transplant Phase 1. High-risk AML for which transplant is recommend based on cytogenetic, molecular and morphologic features. Patients must meet institutional standards for disease control prior to transplant. 2. For MDS. IPSS-revised criteria of high or very high at diagnosis. 3. Subject meets institutional criteria for transplant and has acceptable organ and marrow function as defined below: 1. Serum bilirubin \< 2.0mg/dL unless Gilberts disease 2. Creatinine Clearance \> 45 mL/min.1.73m2 as estimated by modified MDRD equation 3. Left ventricular function 40% or greater 4. DLCO corrected for hemoglobin \>50% 5. KPS 70% or greater 4. An adequate graft for the defined donor type 1. Haplo-cord requires a haploidentical adult donor of 14 years of age and at least 50 kg, and a cord blood unit with at least 1.0 x 10(7) TNC/kg and a match of at least 4/6 by intermediate resolution for HLA-A and B and high resolution at DRB1. Donor provides standard of care consent for harvest following institutional policy. Any donor samples or donor research data would be obtained on separate donor research protocol. 2. For MUD requires a 7/8 or 8/8 HLA matched unrelated donor with high resolution matching at HLA-A, -B, -C, and DRB1. DP matching or DP permissive should be achieved when possible using T-cell epitope strategy. 5. Written informed consent for the transplant phase
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Transplant | Through one year after formal search | Time to transplant will be measured from time of date of formal request to stem cell infusion date. Will also capture time from preliminary search to both formal search and transplant date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Undergo Hematopoietic Cell Transplantation (HCT) | Through one year after formal search | Compare percentage of patients who undergo HCT in each study cohort |
| Estimated Survival Time | From date of randomization up to 3 years | Overall survival time was estimated from date of randomization and from date of transplant using Kaplan-Meier method. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Haplo-Cord Search If subject meets the inclusion criteria and consents, will undergo a haplo-cord transplant.
Haplo-Cord Transplant: For conditioning regimens, haplo-identical grafts will be selected by the Miltenyi Device | 5 |
| Matched Unrelated Donor Search (MUD) If subject meets the inclusion criteria and consents, will undergo a MUD transplant.
Matched Unrelated Donor Transplant | 4 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | No transplant | 3 | 1 |
Baseline characteristics
| Characteristic | Matched Unrelated Donor Search (MUD) | Total | Haplo-Cord Search |
|---|---|---|---|
| Age, Continuous | 61.2 years | 62.1 years | 67.9 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 2 / 3 |
| other Total, other adverse events | 1 / 2 | 2 / 3 |
| serious Total, serious adverse events | 0 / 2 | 0 / 3 |
Outcome results
Primary
Time to Transplant
Time to transplant will be measured from time of date of formal request to stem cell infusion date. Will also capture time from preliminary search to both formal search and transplant date.
Time frame: Through one year after formal search
Population: We analyze only those who went to transplant.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Haplo-Cord Search | Time to Transplant | 69 days |
| Matched Unrelated Donor Search (MUD) | Time to Transplant | 111 days |
Secondary
Estimated Survival Time
Overall survival time was estimated from date of randomization and from date of transplant using Kaplan-Meier method.
Time frame: From date of randomization up to 3 years
Population: We analyzed only those who went transplant.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Haplo-Cord Search | Estimated Survival Time | Days from randomization | 162 days |
| Haplo-Cord Search | Estimated Survival Time | Days from transplant | 92 days |
| Matched Unrelated Donor Search (MUD) | Estimated Survival Time | Days from randomization | 785 days |
| Matched Unrelated Donor Search (MUD) | Estimated Survival Time | Days from transplant | 673 days |
Secondary
Percentage of Patients Who Undergo Hematopoietic Cell Transplantation (HCT)
Compare percentage of patients who undergo HCT in each study cohort
Time frame: Through one year after formal search
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Haplo-Cord Search | Percentage of Patients Who Undergo Hematopoietic Cell Transplantation (HCT) | 2 Participants |
| Matched Unrelated Donor Search (MUD) | Percentage of Patients Who Undergo Hematopoietic Cell Transplantation (HCT) | 3 Participants |