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Phase I/II MAHCT w/ TCell Depleted Graft w/ Simultaneous Infusion Conventional and Regulatory T Cell

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Stanford University
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Everett Meyer, Stanford University Identifier:
First received: August 6, 2012
Last updated: April 18, 2016
Last verified: March 2016
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 addback) 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.

Condition Intervention Phase
Myeloid Leukemia, Chronic
Acute Myelogenous Leukemia
Myelodysplastic Syndromes (MDS)
Lymphoma, Non-Hodgkin
Biological: Conventional T cells (Tcon) and Regulatory T cells (Treg)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial for Patients With Advanced Hematologic Malignancies Undergoing Myeloablative Allogeneic HCT With a T Cell Depleted Graft With Simultaneous Infusion of Conventional T Cells and Regulatory T Cells

Resource links provided by NLM:

Further study details as provided by Stanford University:

Primary Outcome Measures:
  • (Phase II) Event free survival post-HCT [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 54
Study Start Date: December 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose escalation
For the Phase I arm of the study the addition of planned numbers and ratios of Treg compared to Tcon will occur at defined time points after hematopoietic cell infusion. Each cohort will have 3 patients per group. The initial doses and ratios utilized will be 1 x 10^6/kg of T reg cells to 3x10^6/kg of Tcon cells at a 1:3 ratio. In order to progress to the next dose level, there must be no evidence of grade 3 or 4 acute GVHD.
Biological: Conventional T cells (Tcon) and Regulatory T cells (Treg)
A baseline cell dose of conventional T cells of 1x10^6/kg will be used with escalation to the maximum tolerated dose up to 1x10^7/kg
Other Name: Purified regulatory T cells


Ages Eligible for Study:   13 Years to 60 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

Recipient Inclusion Criteria

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

    • Acute leukemia, primary refractory or beyond CR1
    • 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
    • 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. SGPT and SGOT < 2.5 x ULN, unless elevated secondary to disease. 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
  7. Availability of an 6/6 HLA matched sibling defined by Class I (HLA -A and B) serologic typing (or higher resolution) and Class II (HLA-DRB1) molecular typing.
  8. Karnofsky performance status >70%
  9. No prior myeloablative therapy or hematopoietic cell transplantation

Recipient Exclusion Criteria

  1. Seropositive for any of the following: HIV ab, hepatitis B sAg , hep C ab
  2. Uncontrolled bacterial, viral or fungal infection defined as currently taking antimicrobial therapy and progression of clinical symptoms.
  3. Uncontrolled CNS disease involvement
  4. The recipient is pregnant or a lactating female.
  5. 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 Ag, HIV 1 and HIV 2 ab, HTLV 1 and HTLV 2 ab hepatitis B sAg or PCR+ or hepatitis C ab or PCR+ , negative for the Syphillis treponemal screen and negative for HIV 1 and hepatitis C by NAT (nucleic acid testing) within 30 days of apheresis collection
  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 inadequate
  7. The donor or legal guardian greater than 18 years of age, capable of signing an IRB-approved consent form.
  8. Donor selection will be in compliance with 21 CFR 1271.

Donor Exclusion Criteria

  1. Evidence of active infection or viral hepatitis
  2. HIV positive
  3. Lactating female
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01660607

United States, California
Stanford University School of Medicine Palo Alto, California, United States Recruiting
Palo Alto, California, United States, 94305
Contact: Physician Referrals    650-723-0822      
Sub-Investigator: Rajni Agarwal-Hashmi         
Sub-Investigator: Sally Arai         
Sub-Investigator: Jonathan Benjamin         
Sub-Investigator: Laura Johnston         
Sub-Investigator: Robert Lowsky         
Sub-Investigator: Robert S Negrin         
Sub-Investigator: Kevin Sheehan         
Sub-Investigator: Judith Anne Shizuru         
Sub-Investigator: David Miklos         
Sub-Investigator: Wen-Kai Weng         
Principal Investigator: Everett Meyer         
Sponsors and Collaborators
Everett Meyer
National Institutes of Health (NIH)
Principal Investigator: Everett Meyer Stanford University
  More Information

Responsible Party: Everett Meyer, Assistant Professor of Medicine, Stanford University Identifier: NCT01660607     History of Changes
Other Study ID Numbers: BMT236  SU-09142011-8407 
Study First Received: August 6, 2012
Last Updated: April 18, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma, Non-Hodgkin
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders processed this record on October 27, 2016