Acute Leukemia, Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia, Acute Myeloid Leukemia, Chronic Myelogenous Leukemia, Lymphoma, Non-Hodgkin, Myelodysplastic Syndromes (MDS), Myeloid Leukemia, Chronic, Myeloproliferative Syndrome
Conditions
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
Interventions
BIOLOGICALCD34+ Hematopoietic Progenitor Cells (HSPC)
Purified CD34+ hematopoietic progenitor cells used in transplantation.
BIOLOGICALRegulatory T-Cells (Treg)
Highly purified CD4+CD25+CD127-FoxP3+ regulatory T cells to reduce graft-versus-host disease.
BIOLOGICALConventional T-Cells (Tcon)
Conventional CD3+ T cells used for immune reconstitution and graft enhancement.
PROCEDUREMyeloablative Conditioning Regimen
Chemotherapy or total body irradiation used before hematopoietic cell transplantation.
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 73 Years
Healthy volunteers
No
Inclusion criteria
Recipient Inclusion Criteria 1. Patients with the following diseases that are histopathologically confirmed are eligible * Acute leukemia, primary refractory or beyond CR1, or minimal residual disease (MRD) positivity. * High risk acute myeloid leukemia in CR1 with any of the following features: * Complex karyotype(≥3 clonal chromosomal abnormalities) * Any of the following high risk chromosomal abnormalities: * Monosomal karyotype (-5, 5q-, -7, 7q-) * t(11q23), t(9;11), inv(3), t(3;3) t(6;9) t(9;22) * Normal karyotype with fms-like tyrosine kinase 3 (FLT3)-ITD mutation * Other high risk features as determined by molecular studies, or clinical presentation as assessed by the treating physician * Chronic myelogenous leukemia (accelerated, blast or second chronic phase) * Myelodysplastic syndromes * Myeloproliferative syndromes * Non-Hodgkin lymphoma with poor risk features not suitable for autologous HCT 2. Age ≥18 yo and ≤ 60 yo for patients in Cohort 1 only. At the start of Cohort 2A and beyond, eligibility will be expanded to allow pediatric patients age ≥ 13 yo. 3. Cardiac ejection fraction ≥ 45% 4. Lung diffusion capacity ≥ 50% 5. Calculated creatinine clearance ≥ 50 cc/min 6. Serum glutamic-pyruvic transaminase( SGPT) and serum glutamic-oxaloacetic transaminase (SGOT) ≤ 3.0 x ULN (Upper limit of normal), unless elevated secondary to disease. 7. Total bilirubin ≤ 2 x ULN (patients with Gilbert's syndrome may be included at the discretion of the PI or where hemolysis has been excluded 8. Availability of a HLA matched donor (related or unrelated) defined by Class I (HLA-A and B) serologic typing (or higher resolution) and Class II (HLA DRB1) molecular typing. An HLA matched donor is defined for this study to be a sibling that is HLA matched 6/6; or an unrelated donor that is HLA matched 6/6 or 5/6. A sibling may be a half sibling. 9. Karnofsky performance status ≥70% Recipient
Exclusion criteria
1. Seropositive for any of the following: HIV ab; hepatitis B sAg; hepatitis C ab 2. Prior myeloablative therapy or hematopoietic cell transplant 3. Candidate for autologous transplant 4. HIV positive 5. Active uncontrolled bacterial, viral or fungal infection, defined as currently taking antimicrobial therapy and progression of clinical symptoms. 6. Uncontrolled central nervous system (CNS) disease involvement 7. Pregnant or a lactating female 8. Positive serum or urine beta human chorionic gonadotropin (HCG) test in females of childbearing potential within 3 weeks of registration 9. Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow up care Donor Inclusion Criteria 1. Age ≥13 yo and ≤ 75 years 2. Karnofsky performance status of ≥ 70% defined by institutional standards 3. Seronegative for HIV 1 RNA (polymerase chair reaction (PCR); HIV 1 and HIV 2 ab (antibody); HTLV 1 and HTLV 2 ab; PCR+ or sAg (surface antigen) hepatitis B ; or PCR+ or sAg for hepatitis C; negative for the Treponema pallidum antibody Syphilis screen; and negative for HIV 1 and hepatitis C by nucleic acid testing (NAT) within 30 days of apheresis collection. In the case that T pallidum antibody tests are positive, donors must: * Be evaluated and show no evidence of syphilis infection of any stage by physical exam and history * Have completed effective antibiotic therapy to treat syphilis * Have a documented negative non treponemal test (such as RPR) or in the case of a positive non treponemal test must be evaluated by an infectious disease expert to evaluate for alternative causes of test positivity and confirm no evidence of active syphilitic disease 4. Must be 6/6 matched sibling donor as determined by HLA typing 5. Female donors of child-bearing potential must have a negative serum or urine beta-HCG test within three weeks of mobilization 6. Capable of undergoing leukapheresis, have adequate venous access, and be willing to undergo insertion of a central catheter should leukapheresis via peripheral vein be inadequate 7. Agreeable to 2nd donation of Peripheral blood stem cell (PBPC) (or bone marrow harvest) in the event of graft failure 8. The donor or legal guardian greater than 18 years of age, capable of signing an institutional review board (IRB-approved consent form. Donor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1, Phase I: Low Dose Treg + Tcon (Dose Escalation) Participants receive low-dose Treg (1e6 cells/kg) and Tcon (3e6 cells/kg) with CD34+ HSPC.
CD34+ Hematopoietic Progenitor Cells (HSPC): Purified CD34+ hematopoietic progenitor cells used in transplantation.
Regulatory T-Cells (Treg): Highly purified CD4+CD25+CD127-FoxP3+ regulatory T cells to reduce graft-versus-host disease.
Conventional T-Cells (Tcon): Conventional CD3+ T cells used for immune reconstitution and graft enhancement. | 1 |
| Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose Escalation) Participants receive low-dose Treg (1e6 cells/kg) and Tcon (1e6 cells/kg) with CD34+ HSPC.
CD34+ Hematopoietic Progenitor Cells (HSPC): Purified CD34+ hematopoietic progenitor cells used in transplantation.
Regulatory T-Cells (Treg): Highly purified CD4+CD25+CD127-FoxP3+ regulatory T cells to reduce graft-versus-host disease.
Conventional T-Cells (Tcon): Conventional CD3+ T cells used for immune reconstitution and graft enhancement. | 5 |
| Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose Escalation) Participants receive low-dose Treg (up to 3e6 cells/kg), Tcon (3e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
CD34+ Hematopoietic Progenitor Cells (HSPC): Purified CD34+ hematopoietic progenitor cells used in transplantation.
Regulatory T-Cells (Treg): Highly purified CD4+CD25+CD127-FoxP3+ regulatory T cells to reduce graft-versus-host disease.
Conventional T-Cells (Tcon): Conventional CD3+ T cells used for immune reconstitution and graft enhancement.
Myeloablative Conditioning Regimen: Chemotherapy or total body irradiation used before hematopoietic cell transplantation. | 6 |
| Phase 2 , Stage 1 Treg + Tcon With Immunosuppression (Cohort 2A) Participants receive Treg and Tcon therapy with immunosuppressive drugs following myeloablative conditioning.
CD34+ Hematopoietic Progenitor Cells (HSPC): Purified CD34+ hematopoietic progenitor cells used in transplantation.
Regulatory T-Cells (Treg): Highly purified CD4+CD25+CD127-FoxP3+ regulatory T cells to reduce graft-versus-host disease.
Conventional T-Cells (Tcon): Conventional CD3+ T cells used for immune reconstitution and graft enhancement.
Myeloablative Conditioning Regimen: Chemotherapy or total body irradiation used before hematopoietic cell transplantation. | 12 |
| Phase 2, Stage 1 Treg + Tcon Without Immunosuppression (Cohort 2A) Participants receive Treg and Tcon therapy without immunosuppressive drugs following myeloablative conditioning.
CD34+ Hematopoietic Progenitor Cells (HSPC): Purified CD34+ hematopoietic progenitor cells used in transplantation.
Regulatory T-Cells (Treg): Highly purified CD4+CD25+CD127-FoxP3+ regulatory T cells to reduce graft-versus-host disease.
Conventional T-Cells (Tcon): Conventional CD3+ T cells used for immune reconstitution and graft enhancement.
Myeloablative Conditioning Regimen: Chemotherapy or total body irradiation used before hematopoietic cell transplantation. | 12 |
| Phase 2, Phase 2 Treg + Tcon With Immunosuppression (Cohort 2A) Participants receive Treg and Tcon therapy with immunosuppressive drugs following myeloablative conditioning.
CD34+ Hematopoietic Progenitor Cells (HSPC): Purified CD34+ hematopoietic progenitor cells used in transplantation. Regulatory T-Cells (Treg): Highly purified CD4+CD25+CD127-FoxP3+ regulatory T cells to reduce graftversus- host disease. Conventional T-Cells (Tcon): Conventional CD3+ T cells used for immune reconstitution and graft enhancement. Myeloablative Conditioning Regimen: Chemotherapy or total body irradiation used before hematopoietic cell transplantation | 32 |
| Total | 68 |
Baseline characteristics
| Characteristic | Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose Escalation) | Phase 2 , Stage 1 Treg + Tcon With Immunosuppression (Cohort 2A) | Cohort 1, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Phase 2, Stage 1 Treg + Tcon Without Immunosuppression (Cohort 2A) | Phase 2, Phase 2 Treg + Tcon With Immunosuppression (Cohort 2A) | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized < 30 | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 11 Participants | 16 Participants |
| Age, Customized 30 - 39 | 1 Participants | 1 Participants | 4 Participants | 0 Participants | 2 Participants | 2 Participants | 10 Participants |
| Age, Customized 40 - 49 | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 4 Participants | 8 Participants | 18 Participants |
| Age, Customized 50 - 59 | 1 Participants | 3 Participants | 5 Participants | 0 Participants | 3 Participants | 5 Participants | 17 Participants |
| Age, Customized equal or less than 60 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 6 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants | 7 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 11 Participants | 1 Participants | 9 Participants | 25 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 9 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 6 Participants | 11 Participants |
| Race (NIH/OMB) White | 4 Participants | 3 Participants | 10 Participants | 1 Participants | 8 Participants | 17 Participants | 43 Participants |
| Region of Enrollment United States | 5 participants | 6 participants | 12 participants | 1 participants | 12 participants | 32 participants | 68 participants |
| Sex: Female, Male Female | 1 Participants | 6 Participants | 3 Participants | 1 Participants | 3 Participants | 16 Participants | 30 Participants |
| Sex: Female, Male Male | 4 Participants | 0 Participants | 9 Participants | 0 Participants | 9 Participants | 16 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 3 / 5 | 2 / 6 | 3 / 12 | 2 / 12 | 6 / 32 |
| other Total, other adverse events | 0 / 1 | 4 / 5 | 6 / 6 | 11 / 12 | 11 / 12 | 25 / 32 |
| serious Total, serious adverse events | 1 / 1 | 2 / 5 | 6 / 6 | 2 / 12 | 6 / 12 | 10 / 32 |
Outcome results
Primary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1, Phase I: Low Dose Treg + Tcon (Dose Escalation) | GvHD Free Relapse Free Survival (GRFS) | 1 Participants |
| Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose Escalation) | GvHD Free Relapse Free Survival (GRFS) | 1 Participants |
| Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose Escalation) | GvHD Free Relapse Free Survival (GRFS) | 0 Participants |
| Phase 2, Stage 1: Treg + Tcon With Immunosuppression (Cohort 2A) | GvHD Free Relapse Free Survival (GRFS) | 9 Participants |
| Phase 2, Stage 1: Treg + Tcon Without Immunosuppression (Cohort 2A) | GvHD Free Relapse Free Survival (GRFS) | 7 Participants |
| Phase 2, Stage 2: Treg + Tcon With Immunosuppression (Cohort 2A) | GvHD Free Relapse Free Survival (GRFS) | 26 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants Receiving Concomitant Single-Agent Immunosuppression | 0 Participants |
| Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants Receiving Concomitant Single-Agent Immunosuppression | 1 Participants |
| Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose Escalation) | Number of Participants Receiving Concomitant Single-Agent Immunosuppression | 6 Participants |
| Phase 2, Stage 1: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants Receiving Concomitant Single-Agent Immunosuppression | 12 Participants |
| Phase 2, Stage 1: Treg + Tcon Without Immunosuppression (Cohort 2A) | Number of Participants Receiving Concomitant Single-Agent Immunosuppression | 12 Participants |
| Phase 2, Stage 2: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants Receiving Concomitant Single-Agent Immunosuppression | 32 Participants |
Secondary
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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Total DLT Events | 1 Participants |
| Cohort 1, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | ANC <500 | 0 Participants |
| Cohort 1, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 3-5 CRS | 0 Participants |
| Cohort 1, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 4 Acute GvHD | 0 Participants |
| Cohort 1, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 3 Acute GvHD | 1 Participants |
| Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Total DLT Events | 1 Participants |
| Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 3 Acute GvHD | 1 Participants |
| Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | ANC <500 | 1 Participants |
| Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 4 Acute GvHD | 0 Participants |
| Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 3-5 CRS | 0 Participants |
| Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 4 Acute GvHD | 0 Participants |
| Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 3 Acute GvHD | 0 Participants |
| Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Total DLT Events | 0 Participants |
| Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 3-5 CRS | 0 Participants |
| Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose Escalation) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | ANC <500 | 0 Participants |
| Phase 2, Stage 1: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 3 Acute GvHD | 0 Participants |
| Phase 2, Stage 1: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 3-5 CRS | 0 Participants |
| Phase 2, Stage 1: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 4 Acute GvHD | 0 Participants |
| Phase 2, Stage 1: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | ANC <500 | 0 Participants |
| Phase 2, Stage 1: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Total DLT Events | 0 Participants |
| Phase 2, Stage 1: Treg + Tcon Without Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 3-5 CRS | 0 Participants |
| Phase 2, Stage 1: Treg + Tcon Without Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Total DLT Events | 0 Participants |
| Phase 2, Stage 1: Treg + Tcon Without Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 3 Acute GvHD | 2 Participants |
| Phase 2, Stage 1: Treg + Tcon Without Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 4 Acute GvHD | 0 Participants |
| Phase 2, Stage 1: Treg + Tcon Without Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | ANC <500 | 0 Participants |
| Phase 2, Stage 2: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | ANC <500 | 0 Participants |
| Phase 2, Stage 2: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Total DLT Events | 0 Participants |
| Phase 2, Stage 2: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 3 Acute GvHD | 1 Participants |
| Phase 2, Stage 2: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 4 Acute GvHD | 2 Participants |
| Phase 2, Stage 2: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days | Grade 3-5 CRS | 0 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Incidence of Serious Infections | 0 Participants |
| Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Incidence of Serious Infections | 1 Participants |
| Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose Escalation) | Number of Participants With Incidence of Serious Infections | 6 Participants |
| Phase 2, Stage 1: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Incidence of Serious Infections | 3 Participants |
| Phase 2, Stage 1: Treg + Tcon Without Immunosuppression (Cohort 2A) | Number of Participants With Incidence of Serious Infections | 0 Participants |
| Phase 2, Stage 2: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Incidence of Serious Infections | 2 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Overall Survival (OS) at 1 Year | 0 Participants |
| Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Overall Survival (OS) at 1 Year | 2 Participants |
| Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose Escalation) | Number of Participants With Overall Survival (OS) at 1 Year | 6 Participants |
| Phase 2, Stage 1: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Overall Survival (OS) at 1 Year | 11 Participants |
| Phase 2, Stage 1: Treg + Tcon Without Immunosuppression (Cohort 2A) | Number of Participants With Overall Survival (OS) at 1 Year | 10 Participants |
| Phase 2, Stage 2: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Overall Survival (OS) at 1 Year | 28 Participants |
Secondary
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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Moderate cGvHD | 0 Participants |
| Cohort 1, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Milld cGvHD | 0 Participants |
| Cohort 1, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Severe cGvHD | 0 Participants |
| Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Milld cGvHD | 1 Participants |
| Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Moderate cGvHD | 1 Participants |
| Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose Escalation) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Severe cGvHD | 0 Participants |
| Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose Escalation) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Milld cGvHD | 1 Participants |
| Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose Escalation) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Severe cGvHD | 0 Participants |
| Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose Escalation) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Moderate cGvHD | 0 Participants |
| Phase 2, Stage 1: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Moderate cGvHD | 0 Participants |
| Phase 2, Stage 1: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Severe cGvHD | 0 Participants |
| Phase 2, Stage 1: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Milld cGvHD | 1 Participants |
| Phase 2, Stage 1: Treg + Tcon Without Immunosuppression (Cohort 2A) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Milld cGvHD | 1 Participants |
| Phase 2, Stage 1: Treg + Tcon Without Immunosuppression (Cohort 2A) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Moderate cGvHD | 3 Participants |
| Phase 2, Stage 1: Treg + Tcon Without Immunosuppression (Cohort 2A) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Severe cGvHD | 1 Participants |
| Phase 2, Stage 2: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Severe cGvHD | 0 Participants |
| Phase 2, Stage 2: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Milld cGvHD | 6 Participants |
| Phase 2, Stage 2: Treg + Tcon With Immunosuppression (Cohort 2A) | Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months | Moderate cGvHD | 7 Participants |