Clinical trial NCT06047886: UAB 2419-CD34 Selection Using the Automated CliniMACS Prodigy
Official title: Feasibility Study of CD34 Selection for GVHD Prophylaxis Using the Automated CliniMACS
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: AML
ALL
Lymphoid Malignancies
Myelodysplastic Syndromes
CML
Primary Myelofibrosis
Keywords: hematologic malignancies
graft failure
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2023-09-21
Enrollment: 50
Sex: ALL
Minimum age (years): 4
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Feasibility study of CD34 selection for graft versus host disease (GVHD) Prophylaxis using the automated CliniMACS Prodigy Device.
Primary purpose: TREATMENT

Brief summary: Patients with graft failure or delayed engraftment may benefit from a hematopoietic stem cell boost or an additional hematopoietic stem cell transplantation procedure. In such settings standard immune suppression strategies are avoided due to their myelosuppressive nature. Therefore those patients are at increased risk of graft versus host disease, and the infusion of a CD34 selected graft would reduce such a risk. The infusion of CD34 selected graft using CliniMACS plus is currently FDA FDA-approved indication for acute myeloid leukemia. However, the use of the Prodigy would streamline the processing, in terms of hands-off procedure, allowing to provision of this product to the patients without strains on the cell therapy lab team. This procedure has been demonstrated safe and effective in several single-center studies and is currently in advanced phase investigation in several studies for malignant and non-malignant conditions.

Detailed description: Patients eligible to be treated on this status are status post allogeneic hematopoietic stem cell transplantation for a neoplastic hematologic disorder with the need of a CD34 selected stem cell boost for graft failure or low graft function (e.g. marrow cellularity reduced per age and/or dropping donor chimerism with cytopenias and/or platelets or red blood cells transfusion requirement).

Eligibility criteria: Inclusion Criteria:

1. AML in morphologic remission with intermediate/high-risk features or relapsed disease 1 or 2
2. ALL in morphologic remission with high-risk features or relapsed disease 1 or 2
3. Lymphoid malignancies in CR or PR (e.g. non-Hodgkin's lymphoma, prolymphocytic leukemia, CLL)
4. Myelodysplastic syndromes with \<=10% blasts
5. CML in morphologic remission after blast phase or accelerated phase
6. Primary myelofibrosis with \<=10% blasts \^morphologic remission is defined as \<5% blasts on the bone marrow biopsy. Negative test for donor-specific antibody within 28 days of starting conditioning regimen, or adequate for standard desensitization protocol.

Exclusion Criteria:

1. Non-compliant patients.
2. No appropriate caregivers identified.
3. Uncontrolled medical or psychiatric disorders which may preclude patients to undergo clinical studies (Discretion of the attending physician).
4. Patients with known allergy to DMSO.
5. Pregnant or breastfeeding women

Primary outcomes:
measure: Severe acute GVHD
timeFrame: 6 years
measure: extensive chronic GVHD
timeFrame: 6 years
measure: donor chimerism
timeFrame: 6 years
measure: Clinical improvement
timeFrame: 6 years
Secondary outcomes:
measure: Non-relapse mortality
timeFrame: 6 years
measure: Disease relapse
timeFrame: 6 years
measure: overall survival
timeFrame: 6 years
measure: Absolute neutrophil count
timeFrame: 6 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
References:
citation: Locatelli F, Lucarelli B, Merli P. Current and future approaches to treat graft failure after allogeneic hematopoietic stem cell transplantation. Expert Opin Pharmacother. 2014 Jan;15(1):23-36. doi: 10.1517/14656566.2014.852537. Epub 2013 Oct 25.
citation: Pasquini MC, Devine S, Mendizabal A, Baden LR, Wingard JR, Lazarus HM, Appelbaum FR, Keever-Taylor CA, Horowitz MM, Carter S, O'Reilly RJ, Soiffer RJ. Comparative outcomes of donor graft CD34+ selection and immune suppressive therapy as graft-versus-host disease prophylaxis for patients with acute myeloid leukemia in complete remission undergoing HLA-matched sibling allogeneic hematopoietic cell transplantation. J Clin Oncol. 2012 Sep 10;30(26):3194-201. doi: 10.1200/JCO.2012.41.7071. Epub 2012 Aug 6.
citation: Roldan E, Perales MA, Barba P. Allogeneic Stem Cell Transplantation with CD34+ Cell Selection. Clin Hematol Int. 2019 Sep 1;1(3):154-160. doi: 10.2991/chi.d.190613.001. eCollection 2019 Sep.
citation: Spohn G, Wiercinska E, Karpova D, Bunos M, Hummer C, Wingenfeld E, Sorg N, Poppe C, Huppert V, Stuth J, Reck K, Essl M, Seifried E, Bonig H. Automated CD34+ cell isolation of peripheral blood stem cell apheresis product. Cytotherapy. 2015 Oct;17(10):1465-71. doi: 10.1016/j.jcyt.2015.04.005. Epub 2015 May 14.