Clinical trial NCT00959140: Standardization of CD3+ T Cell Dose for Patients Receiving Allogeneic Peripheral Blood Stem Cell Transplantation from Matched Related Donors
Official title: Phase II Study for Standardization of CD3+ T Cell Dose for Patients Receiving Allogeneic Peripheral Blood Stem Cell Transplants from Matched Related Donors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Hematopoietic Stem Cell Transplantation
Keywords: Allo PBSC
HSCT
Bone Marrow Transplant
Allogeneic Bone Marrow Transplant
Matched Related Donor Transplant
MRD HSCT
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: Miltenyi Biotec, Inc.
First posted: 2009-08-14
Enrollment: 20
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence and severity of acute graft versus host disease (aGVHD) with the chosen fixed dose of CD3+ cells
timeFrame: 1 year
Secondary outcomes:
measure: Time to engraftment
timeFrame: 60 days
measure: State of chimerism over time
timeFrame: 2 years
measure: Immune reconstitution over time
timeFrame: 2 years
measure: Incidence, severity and organ involvement with chronic GVHD (cGVHD)
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
measure: Disease free survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Hospital
state: Alabama
Study officials:
affiliation: University of Alabama in Birmingham
name: Ayman Saad, MD
role: PRINCIPAL_INVESTIGATOR
References: