This study looks at giving specific types of immune cells, called regulatory T cells and conventional T cells, to patients with blood cancers who are receiving a stem cell transplant. These cells are added back to help the immune system recover and reduce complications after the transplant.
Primary Objectives: * To determine the efficacy, safety and feasibility of administration of several dose combinations of conventional T cells (Tcon) and regulatory T cells (Treg) in patients undergoing allogeneic hematopoietic cell transplantation (HCT) with HLA matched donors (related or unrelated) using a T cell depleted graft \[CD34+ hematopoietic progenitor cells ("CD34+ HSPC")\], without immune suppression. * To determine if concomitant single-agent immunosuppression is needed with fresh Treg cells (phase 2 stage 1) \* To determine 1-year GvHD-free relapse-free survival (GRFS) post-HCT (phase 2 stage 2). Secondary Objectives: * To determine the 1 year OS in patients undergoing allogeneic HCT with matched donors. * To measure the incidence and severity of acute and chronic graft vs host disease (GvHD) * To measure incidence of serious infections
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
68
Purified CD34+ hematopoietic progenitor cells used in transplantation.
Highly purified CD4+CD25+CD127-FoxP3+ regulatory T cells to reduce graft-versus-host disease.
Conventional CD3+ T cells used for immune reconstitution and graft enhancement.
Chemotherapy or total body irradiation used before hematopoietic cell transplantation.
Stanford University School of Medicine Palo Alto, California, United States
Palo Alto, California, United States
GvHD Free Relapse Free Survival (GRFS)
GvHD-free is defined as no GvHD symptoms, and relapse free survival is defined as survival at 12 months without relapse.
Time frame: 12 months
Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days
Dose-limiting Toxicity (DLT) was assessed as: * Absolute neutrophil count \<500/µL, to 28 day * Cytokine release syndrome/acute infusion reactions as CTCAE Grade 3 to 5 * Grade 3 to 4 acute GvHD. GvHD was staged as follows: * 1: Skin: rash \<25%. Liver: bilirubin (BIL) 2-3mg/dL. Gut: diarrhea (DIA) 500-1000 mL/day * 2: Skin: rash 25-50%. Liver: BIL 3-6mg/dL. Gut: DIA 1001-1500 mL/day * 3: Skin: rash \> 50%. Liver: BIL 6-15mg/dL. Gut: DIA \>1501-2000 mL/day * 4: Skin: generalized erythroderma. Liver: BIL \>15mg/dL. Gut: DIA \>2001 mL/day GvHD was graded as follows. * 1: Skin Stage 1-2; No Liver stage; No Gut stage * 2: Skin Stage 1-3 ; Liver Stage 1; +/- Gut Stage 1 * 3: Skin Stage 2-3, Liver Stage 2-4; +/- Gut Stage 2-3 * 4: Skin Stage 2-4; Liver Stage 2-4; +/- Gut Stage 2-4 The outcome is reported as the number of participants who received both Treg and Tcon cell infusions and had DLT events, per treatment level.
Time frame: 28 days
Number of Participants With Overall Survival (OS) at 1 Year
Overall Survival (OS) at 1 year was assessed as the number of participants per treatment level that received the hematopoietic cell transplant (HCT), and remained alive 12 months later.
Time frame: 1 year
Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months
Incidence and severity of chronic GvHD was assessed in participants who received the hematopoietic cell transplant (HCT) at 24 months.
Time frame: 2 years
Number of Participants With Incidence of Serious Infections
The outcome is reported as the number of serious infections per treatment level, in participants who received the hematopoietic cell transplant (HCT).
Time frame: 24 months
Number of Participants Receiving Concomitant Single-Agent Immunosuppression
During Phase 2, stage 1, concomitant single-agent immunosuppression was assessed as in participants receiving fresh Treg cells.
Time frame: 2 years
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