CD34 Selection Using the Automated CliniMACS Prodigy
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment population Patients 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 will receive a CD34 selected hematopoietic stem cell infusion with or without preceding conditioning. Fludarabine 25 mg/mq day 1 - 5 + 2 Gray Total body irradiation depending on clinician's discretion (with the addition of cyclophosphamide 14.5 mg/kg for two doses for haploidentical or matched unrelated donor with at least one major HLA mismatch). Recommendation to use a conditioning regimen include complete loss of donor chimerism, trilineage cytopenias. |
Drug: Infusion of CD34 selected hematopoietic stem cells
CD34 stem cell isolation and infusion to reduce alloreactive complication of stem cell infusion
|
Outcome Measures
Primary Outcome Measures
- Severe acute GVHD [6 years]
Incidence of severe (grade III-IV) acute GVHD <=25% at 100 days
- extensive chronic GVHD [6 years]
Incidence of extensive chronic GVHD <=10% at one year.
- donor chimerism [6 years]
Improvement of donor chimerism by >=15%
- Clinical improvement [6 years]
Clinical improvement, defined as an increase of blood counts with transfusion independence if anemia or thrombocytopenia or freedom for infections if reduced leukocytes
Secondary Outcome Measures
- Non-relapse mortality [6 years]
Rate of one-year non-relapse mortality (NRM).
- Disease relapse [6 years]
Rate of one-year relapse
- overall survival [6 years]
Rate of one-year overall survival (OS).
- Absolute neutrophil count [6 years]
ANC engraftment or increase
Eligibility Criteria
Criteria
Inclusion Criteria:
-
AML in morphologic remission with intermediate/high-risk features or relapsed disease 1 or 2
-
ALL in morphologic remission with high-risk features or relapsed disease 1 or 2
-
Lymphoid malignancies in CR or PR (e.g. non-Hodgkin's lymphoma, prolymphocytic leukemia, CLL)
-
Myelodysplastic syndromes with <=10% blasts
-
CML in morphologic remission after blast phase or accelerated phase
-
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:
-
Non-compliant patients.
-
No appropriate caregivers identified.
-
Uncontrolled medical or psychiatric disorders which may preclude patients to undergo clinical studies (Discretion of the attending physician).
-
Patients with known allergy to DMSO.
-
Pregnant or breastfeeding women
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35294-3300 |
Sponsors and Collaborators
- University of Alabama at Birmingham
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- IDE29384