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

Not Applicable

Active, not recruiting

• Conditions: Hematopoietic Stem Cell Transplantation
• Interventions: Device: CD3+ T cell depletion

• Registration Number: NCT00959140
• Lead Sponsor: University of Alabama at Birmingham

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2009-08-12
• Study First Submitted QC: 2009-08-12
• Study First Posted: 2009-08-14
• Study Start: 2014-10
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-18
• Last Update Posted: 2024-12-20
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Patients must be ≥19 years of age.
2. Patients must meet all the UAB diagnosis and disease status criteria for clinical appropriateness for myeloablative allo HSCT derived from ASBMT and NCCN guidelines.
3. 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.
4. Adequate organ function: All organ function testing should be done within 28 days of study registration.
5. Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% by MUGA (Multi Gated Acquisition) scan or echocardiogram.
6. 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.
7. 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
8. Performance status: Karnofsky ≥ 70%
9. Hepatic (values to be less than what is considered grade II toxicity per the CTCAE (common terminology criteria for adverse events)

Exclusion criteria

1. 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.

2. HIV positive patients.

3. Prior autologous or allogeneic transplantation for any disease.

4. Scheduled to receive non-myeloablative or reduced intensity conditioning regimen.

5. High Risk Features associated with increased relapse risk or poor outcomes:

   1. AML/ALL: with Bi-phenotypic features
   2. AML: Refractory to Induction and salvage therapy
   3. ALL: Refractory to Induction and salvage therapy
   4. CML: Active blast crisis
   5. HL: Disease refractory to chemotherapy or targeted therapy
   6. NHL: Disease refractory to chemotherapy or targeted therapy

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CD3+ T-cell depletion	CD3+ T cell depletion	CD3+ T-cell depletion

Primary Outcome Measures

Name	Time	Method
Incidence and severity of acute graft versus host disease (aGVHD) with the chosen fixed dose of CD3+ cells	1 year

Secondary Outcome Measures

Name	Time	Method
Immune reconstitution over time	2 years
Overall survival	2 years
Disease free survival	2 years
State of chimerism over time	2 years
Time to engraftment	60 days
Incidence, severity and organ involvement with chronic GVHD (cGVHD)	2 years

Trial Locations

Locations (1)

University of Alabama Hospital; 🇺🇸 Birmingham, Alabama, United States