Phase 1-2 MAHCT w/ TCell Depleted Graft w/ Simultaneous Infusion Conventional and Regulatory T Cell
Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
Details and patient eligibility
About
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.
Full 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
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Recipient Inclusion Criteria
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Patients with the following diseases that are histopathologically confirmed are eligible
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Acute leukemia, primary refractory or beyond CR1, or minimal residual disease (MRD) positivity.
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High risk acute myeloid leukemia in CR1 with any of the following features:
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Complex karyotype(≥3 clonal chromosomal abnormalities)
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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
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Other high risk features as determined by molecular studies, or clinical presentation as assessed by the treating physician
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Chronic myelogenous leukemia (accelerated, blast or second chronic phase)
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Myelodysplastic syndromes
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Myeloproliferative syndromes
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Non-Hodgkin lymphoma with poor risk features not suitable for autologous HCT
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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.
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Cardiac ejection fraction ≥ 45%
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Lung diffusion capacity ≥ 50%
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Calculated creatinine clearance ≥ 50 cc/min
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Serum glutamic-pyruvic transaminase( SGPT) and serum glutamic-oxaloacetic transaminase (SGOT) ≤ 3.0 x ULN (Upper limit of normal), unless elevated secondary to disease.
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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
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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."
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Karnofsky performance status ≥70%
Recipient Exclusion Criteria
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Seropositive for any of the following:
HIV ab; hepatitis B sAg; hepatitis C ab
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Prior myeloablative therapy or hematopoietic cell transplant
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Candidate for autologous transplant
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HIV positive
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Active uncontrolled bacterial, viral or fungal infection, defined as currently taking antimicrobial therapy and progression of clinical symptoms.
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Uncontrolled central nervous system (CNS) disease involvement
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Pregnant or a lactating female
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Positive serum or urine beta human chorionic gonadotropin (HCG) test in females of childbearing potential within 3 weeks of registration
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Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow up care
Donor Inclusion Criteria
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Age ≥13 yo and ≤ 75 years
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Karnofsky performance status of ≥ 70% defined by institutional standards
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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
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Must be 6/6 matched sibling donor as determined by HLA typing
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Female donors of child-bearing potential must have a negative serum or urine beta-HCG test within three weeks of mobilization
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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
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Agreeable to 2nd donation of Peripheral blood stem cell (PBPC) (or bone marrow harvest) in the event of graft failure
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The donor or legal guardian greater than 18 years of age, capable of signing an institutional review board (IRB-approved consent form.
Donor Exclusion Criteria
- Evidence of active infection or viral hepatitis
- HIV positive
- Medical, physical, or psychological reason that would place the donor at increased risk for complications from growth factor or leukapheresis
- Lactating female
Trial design
Primary purpose
Allocation
Interventional model
Masking
68 participants in 9 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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