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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01660607
Recruitment Status : Recruiting
First Posted : August 8, 2012
Last Update Posted : August 11, 2017
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Everett Meyer, Stanford University

Brief Summary:
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 or disease Intervention/treatment 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  (Clinical Trial)
Estimated Enrollment : 54 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : December 2011
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : March 2018

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. (Phase II) Event free survival post-HCT [ Time Frame: 1 year ]

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Ages Eligible for Study:   13 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
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, 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
    • 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 1 RNA 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 palladum antibody Syphillis 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 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 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 inadequate
  7. The donor or legal guardian greater than 18 years of age, capable of signing an IRB-approved consent form.

Donor Exclusion Criteria

  1. Evidence of active infection or viral hepatitis
  2. HIV positive
  3. Lactating female

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01660607

Contact: Physician Referrals 650-723-0822

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

Responsible Party: Everett Meyer, Assistant Professor of Medicine, Stanford University Identifier: NCT01660607     History of Changes
Other Study ID Numbers: BMT236
SU-09142011-8407 ( Other Identifier: Stanford University )
First Posted: August 8, 2012    Key Record Dates
Last Update Posted: August 11, 2017
Last Verified: August 2017

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