Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft
Phase 1 Trial for Patients With Advanced Hematologic Malignancies Undergoing Reduced Intensity Allogeneic HCT With a T-cell Depleted Graft With Infusion of Conventional T-cells and Regulatory T-cells
2 other identifiers
interventional
66
1 country
1
Brief Summary
Reduced intensity conditioning (RIC) has emerged and been increasingly adopted as a modality to allow preparative conditioning pre transplant to be tolerated by older adults or those patients that are otherwise unfit for myeloablative conditioning. In this study, we aim to use RIC followed by matched related/unrelated donor, 7/8 matched related/unrelated donor, or haploidentical donor peripheral blood stem cell transplantation. Standard strategies to control the alloreactivity following HCT utilize immunosuppressive or cytotoxic medications. In this study, we explore donor graft engineering to enrich for immmunoregulatory populations to facilitate post transplantation immune reconstitution while minimizing graft versus host disease (GVHD) with post-transplant immunosuppressive agents.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2021
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 7, 2021
CompletedFirst Submitted
Initial submission to the registry
October 11, 2021
CompletedFirst Posted
Study publicly available on registry
October 21, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 1, 2028
May 12, 2026
May 1, 2026
6.7 years
October 11, 2021
May 8, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Determine the GVHD-free relapse-free survival (GRFS) post-HCT ( Arm-A)
Clinical effect will be assessed as graft vs host disease (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. The outcome will be measured in Arm A only.
12 months
Determine the overall survival (OS) post-HCT ( Arm-B)
Overall survival is measured as number of participants alive. Alive at the time of last observation will be censored.
2 years
Incidence of Grade III-IV acute GVHD
Acute GVHD will be staged and graded per Mount Sinai Acute GvHD International Consortium (MAGIC) Standardization criteria.
At baseline, day +30, 60, 90, 180, year 1 and year 2
The incidence and timing of primary graft failure
Primary graft failure is defined as being alive with donor CD3 chimerism \<5% at day +30 after transplant without recovery of neutrophils (i.e. without achieving an absolute neutrophil count \[ANC\] ≥ 500/mm3 for 3 consecutive days) at Day+28
2 years from the Day 0 (day of CD34+ peripheral blood stem cell infusion
Donor CD3 chimerism at Day+60 post-HCT
Defined as a percentage on donor CD3 cells chimerism at day +60 after transplantation.
2 years from the Day 0 (day of CD34+ peripheral blood stem cell infusion)
Secondary Outcomes (9)
GVHD-relapse-free survival
12 months
Overall survival
12 months
Secondary graft failure
from Day 0 through 100 days
Treatment-emergent adverse events (TEAs)
from Day 0 through 100 days
Acute GVHD (all grades)
from Day 0 through 100 days
- +4 more secondary outcomes
Other Outcomes (3)
Time to Neutrophil engraftment
from Day 0 through 100 days
Time to Platelet engraftment
from Day 0 through 100 days
Incidence of serious infections (grade 2 and greater)
from Day 0 through 100 days
Study Arms (7)
Arm A1: Matched related/matched unrelated donor transplantation (closed)
EXPERIMENTALSubjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant:. * Fludarabine (160 mg/m2) * Melphalan (50 mg/m2) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
Arm B: Haploidentical transplantation (closed)
EXPERIMENTALSubjects without an identified matched related or matched unrelated donor will receive a haploidentical transplantation with reduced intensity preparative conditioning: -. Fludarabine (160 mg/m2) * Melphalan (100 mg/m2 * TBI (4Gy) Patients will receive GVHD prophylaxis with post-transplant cyclophosphamide and tacrolimus.
Arm A2: Fully matched (8/8) related/unrelated donor transplantation (closed)
EXPERIMENTALSubjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
Arm A3: Fully (8/8) matched related/unrelated donor transplantation (closed)
EXPERIMENTALSubjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy). All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
Arm C1:7/8 mismatched related/unrelated donor transplantation (closed)
EXPERIMENTALSubjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and mycophenolate mofetil (MMF).
Arm C2: 7/8 mismatched related/unrelated donor transplantation
EXPERIMENTALSubjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and ruxolitinib.
Arm A4: 8/8 mismatched related/unrelated donor transplantation
EXPERIMENTALSubjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (7.5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus
Interventions
Fludarabine (160 mg/m2)
5 - 8 ng/mL
Thiotepa 10 mg/kg
Ruxolitinib 5 mg BID
Single-use vials contain either 300 mcg or 480 mcg filgrastim at a fill volume of 1.0 mL or 1.6 mL
MMF 1000 mg BID
Melphalan (50 mg/m2)
The CliniMACS® CD34 Reagent System is a medical device that is used in vitro to select and enrich specific cell populations is manufactured by Miltenyi Biotec
4-6ng/mL
40mg/kg
Dose 0.24 mg/kg, manufactured by Genzyme
Purified regulatory T-cells (Treg) plus CD34+ hematopoietic progenitor cells ("CD34+ HSPC"), followed by conventional T-cells (Tcon) Manufactured at SCTT Laboratory, dose 1x10\^6 cells/ kg to 3x10\^6 cells/kg
Eligibility Criteria
You may qualify if:
- Acute myeloid, lymphoid, or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi) or beyond first complete remission (CR1) without the presence of minimal residual disease
- Acute myeloid, leukemia, or mixed phenotype leukemia that is either:
- Not in morphologic CR with bone marrow infiltration by leukemic blasts of ≤10%, or
- In morphologic CR with evidence of minimal residual disease positivity by either multiparametric flow cytometric analysis or by a nucleic acid-based technique
- Primary refractory acute myeloid, lymphoid, or mixed phenotype leukemia
- Chronic myelogenous leukemia (accelerated, blast or second chronic phase)
- Myelodysplastic syndromes
- Myeloproliferative syndromes b. Match to the patient as follows:
- For Arm A1 (CLOSED):
- Availability of a 8/8 or 7/8 HLA-matched donor (related or unrelated) defined by Class I (HLA-A, -B, -C) serologic typing (or higher resolution) and Class II (HLA-DRB1) molecular typing.
- If the donor is a 7/8 HLA-match, the mismatch must be a permissive allelic mismatch as assessed by an independent HLA and transplantation expert.
- For Arm A1 and Arm A3:
- Availability of a 8/8 HLA-matched donor (related or unrelated) defined by Class I (HLA-A, -B, -C) serologic typing (or higher resolution) and Class II (HLA-DRB1) molecular typing.
- For Arm B (CLOSED):
- Availability of a haploidentical donor who is a ≥ 4/8 but \<7/8 match at HLA-A, -B, -C, and -DRB1 (typed using DNA-based high-resolution methods), with at most one mismatch per locus
- +20 more criteria
You may not qualify if:
- Seropositive for any of the following:
- HIV antibodies; hepatitis B surface antigen (sAg); hepatitis C antibodies
- Patients deemed candidates for fully myeloablative preparative conditioning regimens
- d. Candidate for autologous transplant e. Hepatitis B or C with SGPT or SGOT \> 3 x ULN f. HIV-positive g. Active uncontrolled bacterial, viral or fungal infection, defined as currently taking antimicrobial therapy and progression of clinical symptoms. h. Uncontrolled CNS disease involvement i. Pregnant or a lactating female j. Positive serum or urine beta-HCG test in females of childbearing potential within 3 weeks of registration k. Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow-up care l. Known allergy or hypersensitivity to, or intolerance of, tacrolimus m. Positive anti-donor HLA antibodies against a mismatched allele in the selected donor determined by either:
- A positive crossmatch of any titer; or
- The presence of anti-donor HLA antibody to any HLA locus n. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment o. Concurrent malignancies or active disease within 1 year, except nonmelanomatous skin cancers that have been curatively resected
- Evidence of active infection
- Seropositive for HIV-1 or-2, HTLV-1 or -2
- Medical, physical, or psychological reason that would place the donor at increased risk for complications from growth factor or leukapheresis
- Lactating female
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Stanford Universitylead
- Orca Biosystems, Inc.collaborator
Study Sites (1)
Stanford University
Stanford, California, 94304, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Everett Meyer, MD,PhD
Stanford Universiy
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 11, 2021
First Posted
October 21, 2021
Study Start
September 7, 2021
Primary Completion (Estimated)
May 1, 2028
Study Completion (Estimated)
May 1, 2028
Last Updated
May 12, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will not share