Trial Outcomes & Findings for CD34 Selected Allogeneic HCT w/ Myeloablative Conditioning Plus CD8+ Memory TCell Infusion in MDS, AL and CML (NCT NCT04151706)

Last Updated: 2024-10-17

Results Overview

The rate of participants who do not experience GvHD and also do not experience relapse are collectively considered to be GRFS. Relapse will be assessed according to the myelodysplastic syndrome or leukemia response criteria. The participants will be assessed for GRFS though 1 year post transplant. The outcome will be reported as the number of participants, a number without dispersion.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

1 year

Results posted on

2024-10-17

Participant Flow

Participant milestones

Participant milestones
Measure	fTBI/Thiotepa/Fludarabine Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide. CD8+ Memory T Cell Infusion: Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation Thiotepa: 5 mg/kg/day: IV for 2 consecutive days (days -6 to -5) Fludarabine: 25 mg/m2/day: IV for 5 consecutive days (days -6 to -2) Hyperfractionated TBI: Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy) Busulfan: 6 mg/kg/dose Q24h IV. Infused over 3 hours. 1 dose per day x 4 consecutive days x 3.6 mg/kg/dose = 14.4 mg/kg Cyclophosphamide: 60 mg/kg/dose Q24h IV. Infused over 2 hours. 1 dose per day x 2 consecutive days x 60 mg/kg/dose = 120 mg/kg
Overall Study STARTED	7
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

CD34 Selected Allogeneic HCT w/ Myeloablative Conditioning Plus CD8+ Memory TCell Infusion in MDS, AL and CML

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	fTBI/Thiotepa/Fludarabine n=7 Participants Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide. CD8+ Memory T Cell Infusion: Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation Thiotepa: 5 mg/kg/day: IV for 2 consecutive days (days -6 to -5) Fludarabine: 25 mg/m2/day: IV for 5 consecutive days (days -6 to -2) Hyperfractionated TBI: Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy) Busulfan: 6 mg/kg/dose Q24h IV. Infused over 3 hours. 1 dose per day x 4 consecutive days x 3.6 mg/kg/dose = 14.4 mg/kg Cyclophosphamide: 60 mg/kg/dose Q24h IV. Infused over 2 hours. 1 dose per day x 2 consecutive days x 60 mg/kg/dose = 120 mg/kg
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Outcome measures

Outcome measures
Measure	fTBI/Thiotepa/Fludarabine n=7 Participants Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide. CD8+ Memory T Cell Infusion: Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation Thiotepa: 5 mg/kg/day: IV for 2 consecutive days (days -6 to -5) Fludarabine: 25 mg/m2/day: IV for 5 consecutive days (days -6 to -2) Hyperfractionated TBI: Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy) Busulfan: 6 mg/kg/dose Q24h IV. Infused over 3 hours. 1 dose per day x 4 consecutive days x 3.6 mg/kg/dose = 14.4 mg/kg Cyclophosphamide: 60 mg/kg/dose Q24h IV. Infused over 2 hours. 1 dose per day x 2 consecutive days x 60 mg/kg/dose = 120 mg/kg
Number of Participants Achieving Graft-versus-Host Disease-Free and Relapse-Free Survival (GRFS) Through 1 Year Post-Transplant	4 Participants

SECONDARY outcome

Timeframe: 1 year

Graft rejection will be determined on the basis of reaction against the donor hematopoietic cells. The outcome will be reported as the number of participants who experience graft rejection though 1 year post transplant, a number without dispersion

Outcome measures

Outcome measures
Measure	fTBI/Thiotepa/Fludarabine n=7 Participants Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide. CD8+ Memory T Cell Infusion: Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation Thiotepa: 5 mg/kg/day: IV for 2 consecutive days (days -6 to -5) Fludarabine: 25 mg/m2/day: IV for 5 consecutive days (days -6 to -2) Hyperfractionated TBI: Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy) Busulfan: 6 mg/kg/dose Q24h IV. Infused over 3 hours. 1 dose per day x 4 consecutive days x 3.6 mg/kg/dose = 14.4 mg/kg Cyclophosphamide: 60 mg/kg/dose Q24h IV. Infused over 2 hours. 1 dose per day x 2 consecutive days x 60 mg/kg/dose = 120 mg/kg
Number of Participants Experiencing Graft Rejection Through 1 Year Post-Transplant	0 Participants

SECONDARY outcome

Timeframe: 1 year

The participants will be assessed for acute graft versus host disease (GvHD) though 1 year post transplant. The outcome will be reported as the number of participants who experience acute GvHD, a number without dispersion.

Outcome measures

Outcome measures
Measure	fTBI/Thiotepa/Fludarabine n=7 Participants Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide. CD8+ Memory T Cell Infusion: Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation Thiotepa: 5 mg/kg/day: IV for 2 consecutive days (days -6 to -5) Fludarabine: 25 mg/m2/day: IV for 5 consecutive days (days -6 to -2) Hyperfractionated TBI: Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy) Busulfan: 6 mg/kg/dose Q24h IV. Infused over 3 hours. 1 dose per day x 4 consecutive days x 3.6 mg/kg/dose = 14.4 mg/kg Cyclophosphamide: 60 mg/kg/dose Q24h IV. Infused over 2 hours. 1 dose per day x 2 consecutive days x 60 mg/kg/dose = 120 mg/kg
Number of Participants Experiencing Acute Graft-versus-Host Disease (GvHD) Through 1 Year Post-Transplant	3 Participants

SECONDARY outcome

Timeframe: 1 year

Population: The analysis population includes participants who were evaluated for chronic, steroid-requiring GvHD up to 1 year post-transplant. Of the 7 participants initially enrolled, 6 were analyzed for this outcome. One participant was excluded from the analysis due to death from acute GvHD prior to the evaluation of chronic GvHD.

The participants will be assessed for chronic, steroid requiring graft versus host disease (GvHD) though 1 year post transplant. The outcome will be reported as the number of participants who experience chronic GvHD, a number without dispersion.

Outcome measures

Outcome measures
Measure	fTBI/Thiotepa/Fludarabine n=6 Participants Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide. CD8+ Memory T Cell Infusion: Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation Thiotepa: 5 mg/kg/day: IV for 2 consecutive days (days -6 to -5) Fludarabine: 25 mg/m2/day: IV for 5 consecutive days (days -6 to -2) Hyperfractionated TBI: Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy) Busulfan: 6 mg/kg/dose Q24h IV. Infused over 3 hours. 1 dose per day x 4 consecutive days x 3.6 mg/kg/dose = 14.4 mg/kg Cyclophosphamide: 60 mg/kg/dose Q24h IV. Infused over 2 hours. 1 dose per day x 2 consecutive days x 60 mg/kg/dose = 120 mg/kg
Number of Participants With Chronic, Steroid-Requiring Graft-versus-Host Disease (GvHD) Through 1 Year Post-Transplant	0 participants

SECONDARY outcome

Timeframe: 1 year

Non relapse mortality will be assessed as the number of participants who have died though 1 year post transplant, without a relapse or recurrence of their myelodysplastic syndrome or leukemia. Relapse will be assessed according to the myelodysplastic syndrome or leukemia response criteria. The outcome will be reported as the number of affected participants, a number without dispersion.

Outcome measures

Outcome measures
Measure	fTBI/Thiotepa/Fludarabine n=7 Participants Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide. CD8+ Memory T Cell Infusion: Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation Thiotepa: 5 mg/kg/day: IV for 2 consecutive days (days -6 to -5) Fludarabine: 25 mg/m2/day: IV for 5 consecutive days (days -6 to -2) Hyperfractionated TBI: Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy) Busulfan: 6 mg/kg/dose Q24h IV. Infused over 3 hours. 1 dose per day x 4 consecutive days x 3.6 mg/kg/dose = 14.4 mg/kg Cyclophosphamide: 60 mg/kg/dose Q24h IV. Infused over 2 hours. 1 dose per day x 2 consecutive days x 60 mg/kg/dose = 120 mg/kg
Number of Participants With Non-Relapse Mortality Through 1 Year Post-Transplant Without Recurrence of Myelodysplastic Syndrome or Leukemia	1 Participants

SECONDARY outcome

Timeframe: 1 year

Relapse will be assessed according to the myelodysplastic syndrome or leukemia response criteria. The outcome will be reported as the number of participants who experience relapse though 1 year post transplant, a number without dispersion.

Outcome measures

Outcome measures
Measure	fTBI/Thiotepa/Fludarabine n=7 Participants Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide. CD8+ Memory T Cell Infusion: Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation Thiotepa: 5 mg/kg/day: IV for 2 consecutive days (days -6 to -5) Fludarabine: 25 mg/m2/day: IV for 5 consecutive days (days -6 to -2) Hyperfractionated TBI: Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy) Busulfan: 6 mg/kg/dose Q24h IV. Infused over 3 hours. 1 dose per day x 4 consecutive days x 3.6 mg/kg/dose = 14.4 mg/kg Cyclophosphamide: 60 mg/kg/dose Q24h IV. Infused over 2 hours. 1 dose per day x 2 consecutive days x 60 mg/kg/dose = 120 mg/kg
Number of Participants Who Experience Relapse Through 1 Year Post-Transplant	0 Participants

SECONDARY outcome

Timeframe: 1 year

Overall Survival (OS) will be assessed as the number of participants who remain alive at 1 year post transplant. The outcome will be reported as a number without dispersion.

Outcome measures

Outcome measures
Measure	fTBI/Thiotepa/Fludarabine n=7 Participants Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide. CD8+ Memory T Cell Infusion: Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation Thiotepa: 5 mg/kg/day: IV for 2 consecutive days (days -6 to -5) Fludarabine: 25 mg/m2/day: IV for 5 consecutive days (days -6 to -2) Hyperfractionated TBI: Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy) Busulfan: 6 mg/kg/dose Q24h IV. Infused over 3 hours. 1 dose per day x 4 consecutive days x 3.6 mg/kg/dose = 14.4 mg/kg Cyclophosphamide: 60 mg/kg/dose Q24h IV. Infused over 2 hours. 1 dose per day x 2 consecutive days x 60 mg/kg/dose = 120 mg/kg
Overall Survival (OS)	6 Participants

Adverse Events

fTBI/Thiotepa/Fludarabine

Serious events: 1 serious events

Other events: 5 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	fTBI/Thiotepa/Fludarabine n=7 participants at risk Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide. CD8+ Memory T Cell Infusion: Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation Thiotepa: 5 mg/kg/day: IV for 2 consecutive days (days -6 to -5) Fludarabine: 25 mg/m2/day: IV for 5 consecutive days (days -6 to -2) Hyperfractionated TBI: Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy) Busulfan: 6 mg/kg/dose Q24h IV. Infused over 3 hours. 1 dose per day x 4 consecutive days x 3.6 mg/kg/dose = 14.4 mg/kg Cyclophosphamide: 60 mg/kg/dose Q24h IV. Infused over 2 hours. 1 dose per day x 2 consecutive days x 60 mg/kg/dose = 120 mg/kg
Hepatobiliary disorders Steroid refractory liver GVHD	14.3% 1/7 • Number of events 1 • 1 year
Gastrointestinal disorders Anal fistula	14.3% 1/7 • Number of events 1 • 1 year

Other adverse events

Other adverse events
Measure	fTBI/Thiotepa/Fludarabine n=7 participants at risk Participants will be infused on Day 0 with donor derived CD34+ selected cells combined with CD8+CD45RA- T cells {CD Memory T Cells} following a standard myeloablative conditioning regimen that might consist of fTBI, Thiotepa, and Fludarabine or Busulfan and Cyclophosamide. CD8+ Memory T Cell Infusion: Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation Thiotepa: 5 mg/kg/day: IV for 2 consecutive days (days -6 to -5) Fludarabine: 25 mg/m2/day: IV for 5 consecutive days (days -6 to -2) Hyperfractionated TBI: Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy) Busulfan: 6 mg/kg/dose Q24h IV. Infused over 3 hours. 1 dose per day x 4 consecutive days x 3.6 mg/kg/dose = 14.4 mg/kg Cyclophosphamide: 60 mg/kg/dose Q24h IV. Infused over 2 hours. 1 dose per day x 2 consecutive days x 60 mg/kg/dose = 120 mg/kg
Hepatobiliary disorders Acute GvHD	42.9% 3/7 • Number of events 3 • 1 year
Gastrointestinal disorders anal fistula	14.3% 1/7 • Number of events 1 • 1 year
Blood and lymphatic system disorders elevated billirubin	14.3% 1/7 • Number of events 1 • 1 year
Infections and infestations bacteremia	14.3% 1/7 • Number of events 1 • 1 year
Infections and infestations EBV viremia	14.3% 1/7 • Number of events 1 • 1 year
Respiratory, thoracic and mediastinal disorders Fungal Pneumonia	14.3% 1/7 • Number of events 1 • 1 year

Additional Information

Dr. Robert Lowsky

Stanford University

Phone: (650) 723-0822

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place