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Conventional and Regulatory T Cells in Treating Patients with Advanced Hematologic Malignancies Undergoing T Cell-Depleted Donor Stem Cell Transplant

Trial Status: Active

This phase I / II trial studies the side effects and best dose of conventional T cells and regulatory T cells and to see how well they work in treating patients with hematologic malignancies that have spread to other places in the body (advanced) and are undergoing T cell-depleted donor stem cell transplant. Giving chemotherapy and total body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening. Giving an infusion of the donor's T cells (donor lymphocyte infusion) later may help the patient's immune system see any remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect).

Inclusion Criteria

  • Patients with the following diseases that are histopathologically confirmed are eligible * 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 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 or first chronic phase that and has not achieved a molecular remission after three or greater therapies) * Myelodysplastic syndromes * Myeloproliferative syndromes * Non Hodgkin lymphoma with poor risk features not suitable for autologous HCT
  • Left ventricular ejection fraction (LVEF) >= 45%
  • Diffusing capacity of the lungs for carbon monoxide (DLCO) >= 50%
  • Calculated creatinine clearance >= 50 mL/min or creatinine < 2.0 mg/dL
  • Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 x upper limit of normal (ULN), unless elevated secondary to disease
  • Total bilirubin =< 2 x ULN (patients with Gilbert syndrome may be included at the discretion of the principal investigator [PI] or where hemolysis has been excluded)
  • Negative serum or urine beta human chorionic gonadotropin (HCG) test in females of childbearing potential
  • Availability of a 6/6 or 5/6 human leukocyte antigen (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. If the donor is a 5/6 HLA match, the mismatch must be a permissive allelic mismatch as assessed by an independent HLA and transplantation expert
  • Karnofsky performance status >= 70%
  • DONOR: Age >= 13 years old (yo) and =< 75 years
  • DONOR: Karnofsky performance status of >= 70% defined by institutional standards or cleared by the National Marrow Donor Program (NMDP) for NMDP donors
  • DONOR: Seronegative for human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) polymerase chain reaction (PCR), HIV 1 and HIV 2 antibody (ab), human T-cell lymphotropic virus type (HTLV)-1 and HTLV-2 ab; PCR positive (+) or surface antigen (sAg) hepatitis B; or PCR+ or sAg for hepatitis C; negative for the Treponema palladum antibody syphillis screen; and negative for HIV-1 and hepatitis C by nucleic acid testing (NAT) within 40 days of donor apheresis procedures; in the case that Treponema (T) palladum 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 rapid plasma reagin [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
  • DONOR: Must be a related or unrelated, 5/6 or 6/6 HLA match to recipient; if 5/6 HLA matched, must be with permissive allelic HLA mismatch as assessed by an independent HLA and transplantation expert
  • DONOR: Female donors of child-bearing potential must have a negative serum or urine beta-human chorionic gonadotrophin (HCG) test
  • DONOR: 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
  • DONOR: The donor or legal guardian greater than 18 years of age, capable of signing an Institutional Review Board (IRB)-approved consent form
  • DONOR: Agreeable to 2nd donation of peripheral blood stem cell transplantation (PBPC) (or bone marrow harvest) in the event of graft failure
  • DONOR: Meet criteria for donation as specified by standard NMDP guidelines for NMDP unrelated donors

Exclusion Criteria

  • Seropositive for any of the following: human immunodeficiency virus (HIV) antibodies; hepatitis B surface antigen (sAg); hepatitis C antibodies
  • Prior myeloablative therapy or hematopoietic cell transplant
  • Candidate for autologous transplant
  • HIV positive
  • Active uncontrolled bacterial, viral or fungal infection, defined as currently taking antimicrobial therapy and progression of clinical symptoms
  • Uncontrolled central nervous system (CNS) disease involvement
  • Pregnant or a lactating female
  • Positive serum or urine beta HCG test in females of childbearing potential
  • Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow up care
  • DONOR: Evidence of active infection
  • DONOR: HIV-positive
  • DONOR: Medical, physical, or psychological reason that would place the donor at increased risk for complications from growth factor or leukapheresis
  • DONOR: Lactating female


Palo Alto
Stanford Cancer Institute Palo Alto
Status: ACTIVE
Contact: Everett Meyer
Phone: 650-725-5816


I. To determine the efficacy, safety, and feasibility of administration of several dose combinations of conventional T cells (Tcon) and regulatory T cells (Treg) in subjects 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 immunosuppression.

II. To determine the maximum tolerated dose of infused Treg and Tcon cells with myeloablative allogeneic HCT using matching donors.

III. Determine if concomitant single agent immunosuppression is needed with fresh Treg cells (phase 2 stage 1).

IV. To determine 1 year graft-versus-host disease (GvHD) free relapse free survival (GRFS) post HCT (phase 2 stage 2).


I. To determine the 1-year overall survival in patients undergoing allogeneic hematopoietic cell transplantation with matched related donors.

II. To measure the incidence and severity chronic GvHD.

III. To measure incidence of serious infections.


I. To measure immune reconstitution parameters.

OUTLINE: This is a phase I, dose-escalation study of Treg and Tcon followed by a phase II study. Patients with acute leukemia, chronic myelogenous leukemia (high risk), myelodysplastic syndrome, or myeloproliferative disorder are assigned to Regimen I or II and patients with non-Hodgkin lymphoma are assigned to Regimen III.

REGIMEN I: Patients undergo fractionated total-body irradiation (fTBI) on days -8 to -5. Patients also receive etoposide intravenously (IV) on day -4 and cyclophosphamide IV on day -2. Patients then undergo allogeneic CD34+ T-cell depleted HCT on day 0 and infusion of Treg on day 0 and Tcon on day 2.

REGIMEN II: Patients receive busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 to -2. Patients then undergo allogeneic CD34+ T-cell depleted HCT and infusion of Treg and Tcon as in Regimen I.

REGIMEN III: Patients receive carmustine IV on day -6, etoposide IV on day -4, and cyclophosphamide IV on day -2. Patients then undergo allogeneic CD34+ T-cell depleted HCT infusion of Treg and Tcon as in Regimen I.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receiving treatment in Regimens I and III receive sirolimus beginning on day 3; patients receiving treatment in Regimen II receive tacrolimus beginning on day 3.

After completion of study treatment, patients are followed up at 30, 60, 90, 100, 180, and 365 days, and then yearly for 5 years.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Stanford Cancer Institute Palo Alto

Principal Investigator
Everett Meyer

  • Primary ID BMT236
  • Secondary IDs NCI-2011-03025
  • ID NCT01660607