Standardization of CD3+ T Cell Dose for Patients Receiving Allogeneic Peripheral Blood Stem Cell Transplantation From Matched Related Donors

Study Overview
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Brief Summary
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Stem cells collected from sibling donors for allogenic transplants contain various types of cells. The predominant immune cells are called CD3+ T cells. The amount of these T cells vary vastly from donor to donor. This study is to determine if standardizing the CD3+ T cell dose will benefit the recipient (patient). As well as to help discover if dose standardization causes less variation in outcomes between patients and to make transplantation more predictable and complications easier to manage.

Detailed Description
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The optimal CD3+ cell dose to be used for allo HSCT is unknown. In addition, there are multiple variables in addition to CD3+ cell dose which affect engraftment, immune reconstitution, GVH and GVL in these patients including recipient age, diagnosis, disease status at transplantation, donor/recipient tissue type match, preparative regimen, and GVHD prophylaxis. Thus the ability to produce products with a fixed CD3+ content is critical to further research and ultimately to the definition of the right dose of CD3+ cells for various clinical situations. Patients who meet eligibility criteria will receive a peripheral blood stem cell product from their original matched sibling donor engineered to deliver a dose of 3.0+/-0.5 x107 CD3+ cells/kg recipient body weight. Other components of the graft will not be manipulated and the recipient will receive the total number of cells collected with the exception of minimal losses that occur during the process of CD3+ T cell isolation.

Official Title
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Phase II Study for Standardization of CD3+ T Cell Dose for Patients Receiving Allogeneic Peripheral Blood Stem Cell Transplants From Matched Related Donors

Conditions
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Hematopoietic Stem Cell Transplantation

Intervention / Treatment
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* Device: CD3+ T cell depletion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be ≥19 years of age. Patients must meet all the UAB diagnosis and disease status criteria for clinical appropriateness for myeloablative allo HSCT derived from ASBMT and NCCN guidelines. Patients must have a 10/10 HLA matched sibling (excluding identical twin). All donors will be evaluated for eligibility and suitability per standard of care according FACT and NMDP guidelines. Adequate organ function: All organ function testing should be done within 28 days of study registration. Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% by MUGA (Multi Gated Acquisition) scan or echocardiogram. Pulmonary: FEV1 (Forced expiratory volume in 1 second) and FVC (Forced vital capacity) ≥ 50% predicted, DLCO (alveolar diffusion capacity for carbon monoxide) (corrected for hemoglobin) ≥ 50% of predicted. Renal: The estimated creatinine clearance (CrCl) must be equal or greater than 60 mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula Performance status: Karnofsky ≥ 70% Hepatic (values to be less than what is considered grade II toxicity per the CTCAE (common terminology criteria for adverse events) Exclusion criteria Uncontrolled infections, defined as positive blood cultures within 72 hours of study entry, or evidence of progressive infection by imaging studies such as chest CT scan within 14 days of registration. HIV positive patients. Prior autologous or allogeneic transplantation for any disease. Scheduled to receive non-myeloablative or reduced intensity conditioning regimen. High Risk Features associated with increased relapse risk or poor outcomes: AML/ALL: with Bi-phenotypic features AML: Refractory to Induction and salvage therapy ALL: Refractory to Induction and salvage therapy CML: Active blast crisis HL: Disease refractory to chemotherapy or targeted therapy NHL: Disease refractory to chemotherapy or targeted therapy

Ages Eligible for Study
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Minimum Age: 19 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD3+ T-cell depletion<br>CD3+ T-cell depletion | Device: CD3+ T cell depletion<br>* The peripheral blood stem cell product is engineered to deliver a dose of 15 to 20 x10^7 CD3+ cells/kg recipient body weight. Other components of the graft will not be manipulated and the recipient will receive the total number of cells collected with the exception of minimal losses that occur during the process of CD3+ T cell isolation. Following collection, CD3+ T cells will be enumerated and a portion of the product containing 15 to 20 x10^7 CD 3+ cells/kg will be set aside. The remainder of the product will be depleted of CD3+ T cells. Following CD3+ T cell depletion, the CD3+ T cell depleted product will then be combined with the unmanipulated product to provide the specified levels of CD3+ T cells/kg recipient body-weight. The graft is infused into the patient on the same day as selected and within 24 hours of donor aphaeresis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of acute graft versus host disease (aGVHD) with the chosen fixed dose of CD3+ cells |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to engraftment |  | 60 days | 
| State of chimerism over time |  | 2 years | 
| Immune reconstitution over time |  | 2 years | 
| Incidence, severity and organ involvement with chronic GVHD (cGVHD) |  | 2 years | 
| Overall survival |  | 2 years | 
| Disease free survival |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allo PBSC, HSCT, Bone Marrow Transplant, Allogeneic Bone Marrow Transplant, Matched Related Donor Transplant, MRD HSCT