Phase 1-2 MAHCT w/ TCell Depleted Graft w/ Simultaneous Infusion Conventional and Regulatory T Cell

Not Recruiting

Trial ID: NCT01660607


For patients with hematologic malignancies undergoing allogeneic myeloablative (MA) HCT with a T cell depleted graft, the infusion of naturally occurring regulatory T cells with conventional T cells (T cell add back) in pre-defined doses and ratios will reduce the incidence of acute graft vs host disease while augmenting the graft vs leukemia effect and improving immune reconstitution.

Official Title

Phase 1-2 Trial for Patients With Advanced Hematologic Malignancies Undergoing Myeloablative Allogeneic HCT With a T-cell Depleted Graft With Infusion of Conventional T-cells and Regulatory T-cells

Stanford Investigator(s)

Everett Meyer
Everett Meyer

Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy), of Pediatrics (Stem Cell Transplantation) and, by courtesy, of Surgery (Abdominal Transplantation)

Wen-Kai Weng, MD, PhD
Wen-Kai Weng, MD, PhD

Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy) and, by courtesy, of Dermatology

Robert Lowsky
Robert Lowsky

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Judith Shizuru
Judith Shizuru

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy) and of Pediatrics (Stem Cell Transplantation)

Laura Johnston
Laura Johnston

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Robert Negrin
Robert Negrin

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Sally Arai
Sally Arai

Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)


Recipient Inclusion Criteria

   1. Patients with the following diseases that are histopathologically confirmed are

      - Acute leukemia, primary refractory or beyond CR1, or minimal residual disease
      (MRD) positivity.

      - High risk acute myeloid leukemia in CR1 with any of the following features:

      - Complex karyotype(≥3 clonal chromosomal abnormalities)

      - 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

      - Other high risk features as determined by molecular studies, or clinical
      presentation as assessed by the treating physician

      - Chronic myelogenous leukemia (accelerated, blast or second chronic phase)

      - Myelodysplastic syndromes

      - Myeloproliferative syndromes

      - Non-Hodgkin lymphoma with poor risk features not suitable for autologous HCT

   2. 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.

   3. Cardiac ejection fraction ≥ 45%

   4. Lung diffusion capacity ≥ 50%

   5. Calculated creatinine clearance ≥ 50 cc/min

   6. Serum glutamic-pyruvic transaminase( SGPT) and serum glutamic-oxaloacetic transaminase
   (SGOT) ≤ 3.0 x ULN (Upper limit of normal), unless elevated secondary to disease.

   7. 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

   8. 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."

   9. Karnofsky performance status ≥70%

Recipient Exclusion Criteria

   1. Seropositive for any of the following:

   HIV ab; hepatitis B sAg; hepatitis C ab

   2. Prior myeloablative therapy or hematopoietic cell transplant

   3. Candidate for autologous transplant

   4. HIV positive

   5. Active uncontrolled bacterial, viral or fungal infection, defined as currently taking
   antimicrobial therapy and progression of clinical symptoms.

   6. Uncontrolled central nervous system (CNS) disease involvement

   7. Pregnant or a lactating female

   8. Positive serum or urine beta human chorionic gonadotropin (HCG) test in females of
   childbearing potential within 3 weeks of registration

   9. Psychosocial circumstances that preclude the patient being able to go through
   transplant or participate responsibly in follow up care

Donor Inclusion Criteria

   1. Age ≥13 yo and ≤ 75 years

   2. Karnofsky performance status of ≥ 70% defined by institutional standards

   3. 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

      - 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

   4. Must be 6/6 matched sibling donor as determined by HLA typing

   5. Female donors of child-bearing potential must have a negative serum or urine beta-HCG
   test within three weeks of mobilization

   6. Capable of undergoing leukapheresis, have adequate venous access, and be willing to
   undergo insertion of a central catheter should leukapheresis via peripheral vein be

   7. Agreeable to 2nd donation of Peripheral blood stem cell (PBPC) (or bone marrow
   harvest) in the event of graft failure

   8. 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

   1. Evidence of active infection or viral hepatitis

   2. HIV positive

   3. Medical, physical, or psychological reason that would place the donor at increased
   risk for complications from growth factor or leukapheresis

   4. Lactating female


biological: Conventional T cells (Tcon) and Regulatory T cells (Treg)

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
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