Phase I/II MAHCT w/ TCell Depleted Graft w/ Simultaneous Infusion Conventional and Regulatory T Cell
This study is currently recruiting participants.
Verified August 2012 by Stanford University
Sponsor:
Ginna Laport
Collaborator:
Information provided by (Responsible Party):
Ginna Laport, Stanford University
ClinicalTrials.gov Identifier:
NCT01660607
First received: August 6, 2012
Last updated: August 9, 2012
Last verified: August 2012
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Purpose
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:
MedlinePlus related topics:
Acute Myeloid Leukemia
Cancer
Leukemia
Lymphoma
Myelodysplastic Syndromes
U.S. FDA Resources
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
|
Eligibility| Ages Eligible for Study: | 13 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Criteria
Recipient Inclusion Criteria:
Patients with the following diseases that are histopathologically confirmed are eligible
- Acute leukemia, primary refractory or beyond CR1
- Chronic myelogenous leukemia (accelerated, blast or second chronic phase)
- Myelodysplastic syndromes
- Non-Hodgkin lymphoma with poor risk features not suitable for autologous HCT
- Age <= 60 yo
- Cardiac ejection fraction >= 45%
- Lung diffusion capacity >= 50%
- Calculated creatinine clearance >= 50 cc/min
- 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
- Availability of a 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.
- Karnofsky performance status >=70%
- No prior myeloablative therapy or hematopoietic cell transplantation
Recipient Exclusion Criteria
- Seropositive for any of the following: HIV ab, hepatitis B sAg , hep C ab
- Uncontrolled bacterial, viral or fungal infection defined as currently taking antimicrobial therapy and progression of clinical symptoms.
- Uncontrolled CNS disease involvement
- The recipient is pregnant or a lactating female
- Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow up care.
Donor Inclusion Criteria
- Age <= 75 years
- Karnofsky performance status of >=70%
- Medical history and PE confirm good health status as defined by institutional standards
- 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 Syphilis treponemal screen and negative for HIV 1 and hepatitis C by NAT (nucleic acid testing) within 30 days of apheresis collection
- Must be 6/6 matched sibling donor as determined by HLA typing
- Female donors of child-bearing potential must have a negative serum or urine beta-HCG test within three weeks of mobilization
- 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
- The donor or legal guardian greater than 18 years of age, capable of signing an IRB-approved consent form.
Donor Exclusion Criteria
- Evidence of active infection or viral hepatitis
- HIV positive
- Lactating female
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01660607
Contacts
| Contact: Lana Peysakhovich | 650-721-3253 | lpeysakh@stanford.edu |
Locations
| United States, California | |
| Stanford University School of Medicine Palo Alto, California, United States | Recruiting |
| Palo Alto, California, United States, 94305 | |
| Contact: Ginna G Lapport 650-723-0822 ginna.laport@stanford.edu | |
| 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 | |
Sponsors and Collaborators
Ginna Laport
Investigators
| Principal Investigator: | Ginna G Laport | Stanford University |
More Information
No publications provided
| Responsible Party: | Ginna Laport, Assoc Prof-Med Ctr Line, Stanford University |
| ClinicalTrials.gov Identifier: | NCT01660607 History of Changes |
| Other Study ID Numbers: | BMT236, SU-09142011-8407 |
| Study First Received: | August 6, 2012 |
| Last Updated: | August 9, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Lymphoma Lymphoma, Non-Hodgkin Myelodysplastic Syndromes Preleukemia Chronic Disease Neoplasms by Histologic Type Neoplasms |
Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Precancerous Conditions Disease Attributes Pathologic Processes |
ClinicalTrials.gov processed this record on May 23, 2013