CD34 Selection Using the Automated CliniMACS Prodigy

Study Overview
=================
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).

Official Title
-----------------
Feasibility Study of CD34 Selection for GVHD Prophylaxis Using the Automated CliniMACS

Conditions
-----------------
AML, ALL, Lymphoid Malignancies, Myelodysplastic Syndromes, CML, Primary Myelofibrosis

Intervention / Treatment
-----------------
* Drug: Infusion of CD34 selected hematopoietic stem cells


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 4 Weeks
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Feasibility study of CD34 selection for graft versus host disease (GVHD) Prophylaxis using the automated CliniMACS Prodigy Device.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment population<br>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<br>* CD34 stem cell isolation and infusion to reduce alloreactive complication of stem cell infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe acute GVHD | Incidence of severe (grade III-IV) acute GVHD <=25% at 100 days | 6 years | 
| extensive chronic GVHD | Incidence of extensive chronic GVHD <=10% at one year. | 6 years | 
| donor chimerism | Improvement of donor chimerism by >=15% | 6 years | 
| Clinical improvement | Clinical improvement, defined as an increase of blood counts with transfusion independence if anemia or thrombocytopenia or freedom for infections if reduced leukocytes | 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-relapse mortality | Rate of one-year non-relapse mortality (NRM). | 6 years | 
| Disease relapse | Rate of one-year relapse | 6 years | 
| overall survival | Rate of one-year overall survival (OS). | 6 years | 
| Absolute neutrophil count | ANC engraftment or increase | 6 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hematologic malignancies, graft failure