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CompletedNCT04151706Updated Oct 17, 2024Results posted

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

A Phase 2 interventional study of CD8+ Memory T Cell Infusion and Thiotepa in Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndromes, sponsored by Robert Lowsky. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-10-17.

Sponsored by Robert Lowsky · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
7
Allocation
Not applicable
Ages
18 Years to 65 Years
Sex
All
01

Study summary

This study will evaluate combining stem cells from the patient's matched sibling donor (a standard CD34-selected transplant) with a second infusion of white blood cells called "CD8 memory T-cells" from their sibling donor.

Read the detailed description

Primary Objective: To determine the rate of graft versus host disease (GvHD) free, relapse free survival (GRFS) at one year following CD34 selected allogeneic hematopoietic cell transplantation using myeloablative conditioning combined with an infusion of phenotypic CD8+ memory T cells from human leukocyte antigen (HLA) matched donors for patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML).

Secondary Objective: To determine the rate of graft rejection, acute and chronic GvHD, non relapse mortality, relapse, overall survival, and disease free survival.

02

Conditions studied

  • Acute Myeloid Leukemia
  • Acute Lymphoblastic Leukemia
  • Myelodysplastic Syndromes
  • Acute Leukemia
  • Chronic Myeloid Leukemia
03

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 7 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

Robert Lowsky is the lead sponsor of 6 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Eligibility criteria

Recipient Inclusion Criteria:

  • Acute leukemia, in morphologic complete remission, OR myelodysplasia with \< 10% blasts in the marrow, and no circulating blasts that contain auer rods. Patients with chronic myelomonocytic leukemia (CMML) must have a WBC count ≤ 10,000 cells/μL and \< 10% blasts in the marrow.
  • Planned myeloablative conditioning regimen at Stanford University Medical Center.
  • Karnofsky or Lansky Performance Score ≥ 70%.
  • Must have an HLA related donor as follows: onor must be an 8/8 match for HLA A, B and C at intermediate (or higher) resolution, and DRB1 at high resolution using DNA based typing. The donors must be willing to receive G CSF followed by collection of cells by apheresis, and must meet the Program's criteria for donation.
  • Cardiac function: Ejection fraction at rest ≥ 40%.
  • Serum creatinine value of \< 1.5 mg/dL, or an estimated creatinine clearance greater than 50 mL/minute (using the Stanford calculator for eGFR available in EPIC)
  • Diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 50% (adjusted for Hgb)
  • Forced vital capacity (FVC) ≥ 50%.
  • Forced expiratory volume (FEV1) ≥ 50%.
  • Total bilirubin \< 2 times the upper limit of normal (ULN) (unless the elevated bilirubin is attributed to Gilbert's Syndrome)
  • Alanine aminotransferase (ALT) \< 2.5 x ULN
  • Aspartate aminotransferase (AST) \< 2.5 x ULN
  • Total bilirubin \< 2 times the upper limit of normal (unless elevated bilirubin is attributed to Gilbert's Syndrome)
  • Signed informed consent

Recipient Exclusion Criteria:

  • Prior autologous or allogeneic hematopoietic stem cell transplant
  • Prior malignancies, except resected non melanoma or treated cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously is allowed. Cancer treated with curative intent \< 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs
  • Active central nervous system (CNS) involvement by malignant cells
  • Presence of fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated
  • Requirement for supplemental oxygen
  • Uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment
  • History of uncontrolled autoimmune disease or on active treatment (defined as > 5 mg prednisone daily)
  • Seropositive for HIV 1 or 2
  • Seropositive for HTLV I or -II
  • Active Hepatitis B or C viral replication by polymerase chain reaction (PCR)
  • Documented allergy to iron dextran or murine proteins
  • Pregnant (positive serum or urine βHCG) or breastfeeding)
  • Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use an effective form of birth control or abstinence for one year after transplantation
  • Unable to comply with the treatment protocol, including appropriate supportive care, follow up and research tests.
  • Planned to receive post transplant maintenance therapy except for fms-like tyrosine kinase 3 (FLT3) inhibitors or BCR ABL tyrosine kinase inhibitors (TKIs).

Donor Inclusion Criteria:

  • HLA matched donor (matching at 8/8 antigens or alleles including HLA A, B, C, and -DRB1).
  • ≥ 18 years to \< 66.0 years
  • State of general good health
  • Completed a donor evaluation with history, medical examination and standard blood tests within 60 days of starting the hematopoietic cell collection procedure. In order to fairly represent the interests of the donor, the donor evaluation and consent will be performed by a study team member other than the recipient's attending physician.
  • Hepatitis A, B and C, HIV 1 and 2, HTLV, VZV, EBV, HSV, West Nile virus, Syphilis Treponema, T cruzi (Chagas), CMV, and the MPX NAT IDT (HIV/HCV/HBV) will be tested as per national standard of care guidelines for transplant donors. Donors who are HIV positive will be excluded. Donors who are positive by serology for Hepatitis B or C are eligible as long as PCR for RNA/DNA is negative
  • White blood cell count > 3.5 x 109/L
  • Platelets > 150 x 109/L
  • Hematocrit > 35%
  • Capable of undergoing leukapheresis
  • Able to understand and sign informed consent

Donor Exclusion Criteria:

  • Psychological traits or psychological or medical conditions which make them unlikely to tolerate the procedure
  • Pregnant or lactating female
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
7 participants (actual)

Study arms

  • Experimental
    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.

    Drug: CD8+ Memory T Cell Infusion · Drug: Thiotepa · Drug: Fludarabine · Radiation: Hyperfractionated TBI · Drug: Busulfan · Drug: Cyclophosphamide

Interventions

  • DrugCD8+ Memory T Cell Infusion

    Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation

    Also known as: Enriched for CD8+CD45RA memory T cells.

  • DrugThiotepa

    5 mg/kg/day: IV for 2 consecutive days (days -6 to -5)

    Also known as: Tepadina, thiophosphamide, TESPA

  • DrugFludarabine

    25 mg/m2/day: IV for 5 consecutive days (days -6 to -2)

    Also known as: Beneflur

  • RadiationHyperfractionated TBI

    Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy)

  • DrugBusulfan

    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

    Also known as: Busulfanum

  • DrugCyclophosphamide

    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

    Also known as: Cytoxan, Neosar

06

What researchers measure

Primary outcomes

  1. Number of Participants Achieving Graft-versus-Host Disease-Free and Relapse-Free Survival (GRFS) Through 1 Year Post-Transplant

    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.

    Time frame: 1 year

Secondary outcomes

  1. Number of Participants Experiencing Graft Rejection Through 1 Year Post-Transplant

    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

    Time frame: 1 year

  2. Number of Participants Experiencing Acute Graft-versus-Host Disease (GvHD) Through 1 Year Post-Transplant

    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.

    Time frame: 1 year

  3. Number of Participants With Chronic, Steroid-Requiring Graft-versus-Host Disease (GvHD) Through 1 Year Post-Transplant

    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.

    Time frame: 1 year

  4. Number of Participants With Non-Relapse Mortality Through 1 Year Post-Transplant Without Recurrence of Myelodysplastic Syndrome or Leukemia

    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.

    Time frame: 1 year

  5. Number of Participants Who Experience Relapse Through 1 Year Post-Transplant

    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.

    Time frame: 1 year

  6. Overall Survival (OS)

    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.

    Time frame: 1 year

07

Results

Posted Oct 17, 2024

Participant flow

Participant flow — Overall Study
MilestonefTBI/Thiotepa/Fludarabine
Started7
Completed7
Not completed0

Outcome measures

PrimaryNumber of Participants Achieving Graft-versus-Host Disease-Free and Relapse-Free Survival (GRFS) Through 1 Year Post-Transplant

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.

Time frame:
1 year
Reported as:
Count of participants · Participants
Number of Participants Achieving Graft-versus-Host Disease-Free and Relapse-Free Survival (GRFS) Through 1 Year Post-Transplant
ParticipantsfTBI/Thiotepa/Fludarabine
Number of Participants Achieving Graft-versus-Host Disease-Free and Relapse-Free Survival (GRFS) Through 1 Year Post-Transplant4
SecondaryNumber of Participants Experiencing Graft Rejection Through 1 Year Post-Transplant

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

Time frame:
1 year
Reported as:
Count of participants · Participants
Number of Participants Experiencing Graft Rejection Through 1 Year Post-Transplant
ParticipantsfTBI/Thiotepa/Fludarabine
Number of Participants Experiencing Graft Rejection Through 1 Year Post-Transplant0
SecondaryNumber of Participants Experiencing Acute Graft-versus-Host Disease (GvHD) Through 1 Year Post-Transplant

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.

Time frame:
1 year
Reported as:
Count of participants · Participants
Number of Participants Experiencing Acute Graft-versus-Host Disease (GvHD) Through 1 Year Post-Transplant
ParticipantsfTBI/Thiotepa/Fludarabine
Number of Participants Experiencing Acute Graft-versus-Host Disease (GvHD) Through 1 Year Post-Transplant3
SecondaryNumber of Participants With Chronic, Steroid-Requiring Graft-versus-Host Disease (GvHD) Through 1 Year Post-Transplant

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.

Time frame:
1 year
Reported as:
Number · participants
Number of Participants With Chronic, Steroid-Requiring Graft-versus-Host Disease (GvHD) Through 1 Year Post-Transplant
participantsfTBI/Thiotepa/Fludarabine
Number of Participants With Chronic, Steroid-Requiring Graft-versus-Host Disease (GvHD) Through 1 Year Post-Transplant0
SecondaryNumber of Participants With Non-Relapse Mortality Through 1 Year Post-Transplant Without Recurrence of Myelodysplastic Syndrome or Leukemia

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.

Time frame:
1 year
Reported as:
Count of participants · Participants
Number of Participants With Non-Relapse Mortality Through 1 Year Post-Transplant Without Recurrence of Myelodysplastic Syndrome or Leukemia
ParticipantsfTBI/Thiotepa/Fludarabine
Number of Participants With Non-Relapse Mortality Through 1 Year Post-Transplant Without Recurrence of Myelodysplastic Syndrome or Leukemia1
SecondaryNumber of Participants Who Experience Relapse Through 1 Year Post-Transplant

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.

Time frame:
1 year
Reported as:
Count of participants · Participants
Number of Participants Who Experience Relapse Through 1 Year Post-Transplant
ParticipantsfTBI/Thiotepa/Fludarabine
Number of Participants Who Experience Relapse Through 1 Year Post-Transplant0
SecondaryOverall Survival (OS)

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.

Time frame:
1 year
Reported as:
Count of participants · Participants
Overall Survival (OS)
ParticipantsfTBI/Thiotepa/Fludarabine
Overall Survival (OS)6

Adverse events

Collected over 1 year. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
fTBI/Thiotepa/Fludarabine1/7 (14.3%)1/7 (14.3%)5/7 (71.4%)
Most frequent serious events
Most frequent serious events
EventfTBI/Thiotepa/Fludarabine
Steroid refractory liver GVHDHepatobiliary disorders1/7
Anal fistulaGastrointestinal disorders1/7
Most frequent other events
Most frequent other events
EventfTBI/Thiotepa/Fludarabine
Acute GvHDHepatobiliary disorders3/7
anal fistulaGastrointestinal disorders1/7
elevated billirubinBlood and lymphatic system disorders1/7
bacteremiaInfections and infestations1/7
EBV viremiaInfections and infestations1/7
Fungal PneumoniaRespiratory, thoracic and mediastinal disorders1/7

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)fTBI/Thiotepa/Fludarabine
<=18 years0
Between 18 and 65 years7
>=65 years0
Sex: Female, Male
Sex: Female, Male(Participants)fTBI/Thiotepa/Fludarabine
Female1
Male6
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)fTBI/Thiotepa/Fludarabine
Hispanic or Latino4
Not Hispanic or Latino3
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)fTBI/Thiotepa/Fludarabine
American Indian or Alaska Native0
Asian2
Native Hawaiian or Other Pacific Islander0
Black or African American0
White2
More than one race0
Unknown or Not Reported3
Region of Enrollment
Region of Enrollment(participants)fTBI/Thiotepa/Fludarabine
United States7
08

Study locations

1 site
  • Stanford Medical Center
    Stanford, California 94304, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Feb 12, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 17, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04151706
Lead sponsor
Robert Lowsky
Collaborators
National Institutes of Health (NIH), National Cancer Institute (NCI)
Responsible party
Robert Lowsky (Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy), Stanford University) — Sponsor-investigator
First posted
Nov 5, 2019
Start date
Feb 27, 2020
Primary completion
Sep 8, 2023
Completion
Sep 8, 2023
Results posted
Oct 17, 2024
Last update
Oct 17, 2024

Study contacts

Robert Lowsky, MD
principal investigator · Stanford Medical Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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