- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04151706
CD34 Selected Allogeneic HCT w/ Myeloablative Conditioning Plus CD8+ Memory TCell Infusion in MDS, AL and CML
CD34 Selected Allogeneic Hematopoietic Cell Transplantation With Myeloablative Conditioning and CD8+ Memory T Cell Infusion For Patients With Myelodysplastic Syndrome, Acute Leukemia, and Chronic Myelogenous Leukemia
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Stanford, California, United States, 94304
- Stanford Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Allogeneic phenotypic CD8+ memory T cells from HLA matched donors infused at the time of hematopoietic cell transplantation
Other Names:
5 mg/kg/day: IV for 2 consecutive days (days -6 to -5)
Other Names:
25 mg/m2/day: IV for 5 consecutive days (days -6 to -2)
Other Names:
Administered in 11 fractions of 125 cGy over 4 days (Total dose of 1375 cGy)
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
Other Names:
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
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Graft versus Host Disease (GvHD) free and relapse free survival (GRFS)
Time Frame: 1 year
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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.
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1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Graft Rejection
Time Frame: 1 year
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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
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1 year
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Acute Graft versus Host Disease (GvHD)
Time Frame: 1 year
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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.
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1 year
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Chronic Graft versus Host Disease (GvHD)
Time Frame: 1 year
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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.
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1 year
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Non relapse Mortality
Time Frame: 1 year
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: 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.
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1 year
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Relapse
Time Frame: 1 year
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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.
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1 year
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Overall Survival (OS)
Time Frame: 1 year
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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.
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1 year
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Robert Lowsky, MD, Stanford Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Precancerous Conditions
- Leukemia, Lymphoid
- Chronic Disease
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Preleukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
- Fludarabine
- Thiotepa
- Busulfan
Other Study ID Numbers
- IRB-49023 (Other Identifier: Stanford IRB)
- BMT339 (Other Identifier: OnCore)
- P01CA049605 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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