Phase 1-2 MAHCT w/ TCell Depleted Graft w/ Simultaneous Infusion Conventional and Regulatory T Cell

Phase 1

Completed

Conditions: Acute Leukemia
Myelodysplastic Syndromes (MDS)
Acute Myelogenous Leukemia
Myeloid Leukemia, Chronic
Acute Lymphoblastic Leukemia (ALL)
Acute Myeloid Leukemia
Chronic Myelogenous Leukemia
Lymphoma, Non-Hodgkin
Myeloproliferative Syndrome

Interventions: Biological: CD34+ Hematopoietic Progenitor Cells (HSPC)
Biological: Regulatory T-Cells (Treg)
Biological: Conventional T-Cells (Tcon)
Procedure: Myeloablative Conditioning Regimen

Registration Number: NCT01660607

Lead Sponsor: Stanford University

Brief Summary: 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.

Detailed Description: 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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 68

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 3A, Phase I: High Dose Treg + Tcon (Dose escalation)	Conventional T-Cells (Tcon)	Participants receive high-dose Treg (1e6 cells/kg), Tcon (1e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 3A, Phase I: High Dose Treg + Tcon (Dose escalation)	Myeloablative Conditioning Regimen	Participants receive high-dose Treg (1e6 cells/kg), Tcon (1e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Phase 2: Myeloablative HCT Control	CD34+ Hematopoietic Progenitor Cells (HSPC)	Participants receive standard myeloablative conditioning with CD34+ HSPC and no experimental Treg or Tcon.
Phase 2: Myeloablative HCT Control	Myeloablative Conditioning Regimen	Participants receive standard myeloablative conditioning with CD34+ HSPC and no experimental Treg or Tcon.
Cohort 1, Phase I: Low Dose Treg + Tcon (Dose escalation)	CD34+ Hematopoietic Progenitor Cells (HSPC)	Participants receive low-dose Treg (1e6 cells/kg) and Tcon (3e6 cells/kg) with CD34+ HSPC.
Cohort 1, Phase I: Low Dose Treg + Tcon (Dose escalation)	Regulatory T-Cells (Treg)	Participants receive low-dose Treg (1e6 cells/kg) and Tcon (3e6 cells/kg) with CD34+ HSPC.
Cohort 1, Phase I: Low Dose Treg + Tcon (Dose escalation)	Conventional T-Cells (Tcon)	Participants receive low-dose Treg (1e6 cells/kg) and Tcon (3e6 cells/kg) with CD34+ HSPC.
Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose escalation)	CD34+ Hematopoietic Progenitor Cells (HSPC)	Participants receive low-dose Treg (1e6 cells/kg) and Tcon (1e6 cells/kg) with CD34+ HSPC.
Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose escalation)	Regulatory T-Cells (Treg)	Participants receive low-dose Treg (1e6 cells/kg) and Tcon (1e6 cells/kg) with CD34+ HSPC.
Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose escalation)	Conventional T-Cells (Tcon)	Participants receive low-dose Treg (1e6 cells/kg) and Tcon (1e6 cells/kg) with CD34+ HSPC.
Cohort 2, Phase 1: Mid Dose Treg + Tcon (Dose escalation)	CD34+ Hematopoietic Progenitor Cells (HSPC)	Participants receive low-dose Treg (3e6 cells/kg), Tcon (1e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 2, Phase 1: Mid Dose Treg + Tcon (Dose escalation)	Regulatory T-Cells (Treg)	Participants receive low-dose Treg (3e6 cells/kg), Tcon (1e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 2, Phase 1: Mid Dose Treg + Tcon (Dose escalation)	Conventional T-Cells (Tcon)	Participants receive low-dose Treg (3e6 cells/kg), Tcon (1e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 2, Phase 1: Mid Dose Treg + Tcon (Dose escalation)	Myeloablative Conditioning Regimen	Participants receive low-dose Treg (3e6 cells/kg), Tcon (1e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose escalation)	CD34+ Hematopoietic Progenitor Cells (HSPC)	Participants receive low-dose Treg (up to 3e6 cells/kg), Tcon (3e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose escalation)	Regulatory T-Cells (Treg)	Participants receive low-dose Treg (up to 3e6 cells/kg), Tcon (3e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose escalation)	Conventional T-Cells (Tcon)	Participants receive low-dose Treg (up to 3e6 cells/kg), Tcon (3e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose escalation)	Myeloablative Conditioning Regimen	Participants receive low-dose Treg (up to 3e6 cells/kg), Tcon (3e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 3, Phase I: High Dose Treg + Tcon (Dose escalation)	CD34+ Hematopoietic Progenitor Cells (HSPC)	Participants receive high-dose Treg (3e6 cells/kg), Tcon (3e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 3, Phase I: High Dose Treg + Tcon (Dose escalation)	Regulatory T-Cells (Treg)	Participants receive high-dose Treg (3e6 cells/kg), Tcon (3e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 3, Phase I: High Dose Treg + Tcon (Dose escalation)	Conventional T-Cells (Tcon)	Participants receive high-dose Treg (3e6 cells/kg), Tcon (3e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 3, Phase I: High Dose Treg + Tcon (Dose escalation)	Myeloablative Conditioning Regimen	Participants receive high-dose Treg (3e6 cells/kg), Tcon (3e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 3A, Phase I: High Dose Treg + Tcon (Dose escalation)	CD34+ Hematopoietic Progenitor Cells (HSPC)	Participants receive high-dose Treg (1e6 cells/kg), Tcon (1e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 3A, Phase I: High Dose Treg + Tcon (Dose escalation)	Regulatory T-Cells (Treg)	Participants receive high-dose Treg (1e6 cells/kg), Tcon (1e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Phase 2 Treg + Tcon with Immunosuppression	CD34+ Hematopoietic Progenitor Cells (HSPC)	Participants receive Treg and Tcon therapy with immunosuppressive drugs following myeloablative conditioning.
Phase 2 Treg + Tcon with Immunosuppression	Regulatory T-Cells (Treg)	Participants receive Treg and Tcon therapy with immunosuppressive drugs following myeloablative conditioning.
Phase 2 Treg + Tcon with Immunosuppression	Conventional T-Cells (Tcon)	Participants receive Treg and Tcon therapy with immunosuppressive drugs following myeloablative conditioning.
Phase 2 Treg + Tcon with Immunosuppression	Myeloablative Conditioning Regimen	Participants receive Treg and Tcon therapy with immunosuppressive drugs following myeloablative conditioning.
Phase 2 Treg + Tcon without Immunosuppression	CD34+ Hematopoietic Progenitor Cells (HSPC)	Participants receive Treg and Tcon therapy without immunosuppressive drugs following myeloablative conditioning.
Phase 2 Treg + Tcon without Immunosuppression	Regulatory T-Cells (Treg)	Participants receive Treg and Tcon therapy without immunosuppressive drugs following myeloablative conditioning.
Phase 2 Treg + Tcon without Immunosuppression	Conventional T-Cells (Tcon)	Participants receive Treg and Tcon therapy without immunosuppressive drugs following myeloablative conditioning.
Phase 2 Treg + Tcon without Immunosuppression	Myeloablative Conditioning Regimen	Participants receive Treg and Tcon therapy without immunosuppressive drugs following myeloablative conditioning.

Primary Outcome Measures

Name	Time	Method
GvHD Free Relapse Free Survival (GRFS)	12 months	GvHD-free is defined as no GvHD symptoms, and relapse free survival is defined as survival at 12 months without relapse.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days	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.
Number of Participants With Overall Survival (OS) at 1 Year	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.
Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months	2 years	Incidence and severity of chronic GvHD was assessed in participants who received the hematopoietic cell transplant (HCT) at 24 months.
Number of Participants With Incidence of Serious Infections	24 months	The outcome is reported as the number of serious infections per treatment level, in participants who received the hematopoietic cell transplant (HCT).
Number of Participants Receiving Concomitant Single-Agent Immunosuppression	2 years	During Phase 2, stage 1, concomitant single-agent immunosuppression was assessed as in participants receiving fresh Treg cells.

Trial Locations

Locations (1): Stanford University School of Medicine Palo Alto, California, United States
🇺🇸
Palo Alto, California, United States
Stanford University School of Medicine Palo Alto, California, United States
🇺🇸Palo Alto, California, United States