The Rapid Study: Randomized Phase II Study To Expedite Allogeneic Transplant With Immediate Haploidentical Plus Unrelated Cord Donor Search Versus Matched Unrelated Donor Search For AML And High-Risk MDS Patients

Study Overview
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Brief Summary
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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
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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

Official Title
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The Rapid Study: Randomized (RA) Phase (P) II Study To Expedite Allogeneic Transplant With Immediate (I) Haploidentical Plus Unrelated Cord Donor (D) Search Versus Matched Unrelated Donor Search For AML And High-Risk MDS Patients

Conditions
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Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS)

Intervention / Treatment
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* Biological: Haplo-Cord Transplant
* Procedure: Matched Unrelated Donor Transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Search Phase: Diagnosis of acute myeloid leukemia (AML) or high or very high-risk MDS by international prognostic scoring system revised for whom transplant is recommended 18 years of age or older 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). 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) Ability to understand and the willingness to sign a written informed consent document for the Search Phase. Patient willing to consider HCT A preliminary search has identified: 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 At least one potential 8/8 HLA-matched (HLA-A, -B, -C, and -DRB1) unrelated donor with a probability of 70% AND Availability of a potential related haploidentical donor. Exclusion Criteria for Search Phase: Prior formal search was instituted Diagnosis of acute promyelocytic leukemia (APL) Known HLA matched related donor without contraindications to donate Life expectancy severely limited by concomitant illness or uncontrolled infection Inclusion Criteria for Transplant Phase 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. For MDS. IPSS-revised criteria of high or very high at diagnosis. Subject meets institutional criteria for transplant and has acceptable organ and marrow function as defined below: Serum bilirubin < 2.0mg/dL unless Gilberts disease Creatinine Clearance > 45 mL/min.1.73m2 as estimated by modified MDRD equation Left ventricular function 40% or greater DLCO corrected for hemoglobin >50% KPS 70% or greater An adequate graft for the defined donor type 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. 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. Written informed consent for the transplant phase Exclusion Criteria for Transplant Phase Life expectancy severely limited by concomitant illness or uncontrolled infection HIV-positive

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Haplo-Cord Search<br>If subject meets the inclusion criteria and consents, will undergo a haplo-cord transplant. | Biological: Haplo-Cord Transplant<br>* For conditioning regimens, haplo-identical grafts will be selected by the Miltenyi Device<br>|
| Other: Matched Unrelated Donor Search (MUD)<br>If subject meets the inclusion criteria and consents, will undergo a MUD transplant. | Procedure: Matched Unrelated Donor Transplant<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Through one year after formal search | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Undergo Hematopoietic Cell Transplantation (HCT) | Compare percentage of patients who undergo HCT in each study cohort | Through one year after formal search | 
| Estimated Survival Time | Overall survival time was estimated from date of randomization and from date of transplant using Kaplan-Meier method. | From date of randomization up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myeloid Leukemia (AML), High-Risk Myelodysplastic Syndrome (MDS), hematopoietic cell transplantation, haplo-cord search, matched unrelated donor search