Infusion of Allogeneic CD19-Specific T Cells From Peripheral Blood

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01497184
First received: December 20, 2011
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

The goal of this clinical research study is to learn if researchers can successfully and safely give HSCT patients an infusion of white blood cells (called T-cells) that have been genetically changed. The process of changing the DNA (the genetic material in cells) of these T-cells is called "gene transfer." Researchers want to learn if these genetically-changed T-cells are effective in attacking cancer cells in patients with advanced B-cell lymphoma or leukemia, after they have received standard allogeneic HSCT. Researchers want to find out the highest dose of these special T-cells that can be given safely to leukemia and lymphoma patients. Researchers also want to learn how long the changed T-cells stay in your body, and if adding them to standard transplant can improve how you respond to treatment.


Condition Intervention Phase
Leukemia
Lymphoma
Procedure: HSCT
Genetic: DLI
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: CD19-Specific T Cell Infusion in Patients With B-Lineage Lymphoid Malignancies After Allogeneic Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated dose (MTD) of Donor Lymphocyte Infusion (DLI) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    MTD is highest dose level where 2 of 6 treated participants have dose limiting toxicity (DLT). DLT defined as new adverse event attributable to donor lymphocyte infusion (DLI) grade 3 or > involving cardiopulmonary, gastrointestinal, hepatic (excluding albumin), neurological, or renal common toxicity criteria (CTC) version 4 parameters, lasts > 3 days and possibly related to DLI within 30 days of infusion.


Estimated Enrollment: 96
Study Start Date: December 2011
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DLI (Adults)
Arm 1: Allogeneic donor lymphocyte infusion (DLI) starting dose not to exceed 10^6/m^2 intravenously (IV) between 6 weeks - 12 weeks following date of allogeneic hematopoietic stem-cell transplantation (HSCT) as a planned DLI.
Procedure: HSCT
Hematopoietic stem-cell transplant using cells from a matched family donor (matched related allogeneic HSCT) using a non-T cell depleted graft under standard of care procedures
Other Names:
  • bone marrow transplant
  • HSCT
  • Hematopoietic stem-cell transplant
Genetic: DLI
Allogeneic donor lymphocyte infusion (DLI) starting dose not to exceed 10^6/m^2 intravenously between 6 weeks and 12 weeks following allogeneic HSCT.
Other Names:
  • Allogeneic donor lymphocyte infusion
  • DLI
  • CD19-specific T cell Infusion
Experimental: DLI any time
Arm 2: DLI will be administered at any point after disease recurrence following HSCT.
Procedure: HSCT
Hematopoietic stem-cell transplant using cells from a matched family donor (matched related allogeneic HSCT) using a non-T cell depleted graft under standard of care procedures
Other Names:
  • bone marrow transplant
  • HSCT
  • Hematopoietic stem-cell transplant
Genetic: DLI
Allogeneic donor lymphocyte infusion (DLI) starting dose not to exceed 10^6/m^2 intravenously between 6 weeks and 12 weeks following allogeneic HSCT.
Other Names:
  • Allogeneic donor lymphocyte infusion
  • DLI
  • CD19-specific T cell Infusion
Experimental: DLI Pediatrics
Arm 3: DLI administered intravenously between 6 weeks and 12 weeks following date of HSCT as a planned DLI in pediatric patients, aged 1-17 years-old.
Procedure: HSCT
Hematopoietic stem-cell transplant using cells from a matched family donor (matched related allogeneic HSCT) using a non-T cell depleted graft under standard of care procedures
Other Names:
  • bone marrow transplant
  • HSCT
  • Hematopoietic stem-cell transplant
Genetic: DLI
Allogeneic donor lymphocyte infusion (DLI) starting dose not to exceed 10^6/m^2 intravenously between 6 weeks and 12 weeks following allogeneic HSCT.
Other Names:
  • Allogeneic donor lymphocyte infusion
  • DLI
  • CD19-specific T cell Infusion
Experimental: DLI - Haplo-Identical Family Donor
Arm 4: DLI administered as planned DLI or after recurrence in adult and pediatric patients undergoing transplant with a haplo-identical family donor.
Procedure: HSCT
Hematopoietic stem-cell transplant using cells from a matched family donor (matched related allogeneic HSCT) using a non-T cell depleted graft under standard of care procedures
Other Names:
  • bone marrow transplant
  • HSCT
  • Hematopoietic stem-cell transplant
Genetic: DLI
Allogeneic donor lymphocyte infusion (DLI) starting dose not to exceed 10^6/m^2 intravenously between 6 weeks and 12 weeks following allogeneic HSCT.
Other Names:
  • Allogeneic donor lymphocyte infusion
  • DLI
  • CD19-specific T cell Infusion

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with a history of CD19+ lymphoid malignancies that are primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease. Patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time:1) Acute Lymphoblastic Leukemia (ALL) with translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure,and/or evidence of minimal residual disease, 2) acute biphenotypic leukemia, or 3) double hit nonHodgkin's lymphoma. Non-Hodgkin's Lymphoma (NHL) in second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant). Double hit lymphomas in first remission or more advanced disease. Small Lymphocytic Lymphoma (SLL), or Chronic Lymphocytic Leukemia (CLL) with progressive disease following standard therapy.
  2. Age 1 to 65 years old.
  3. Lansky performance score >/= 60% for patients </= 16 years of age, or Zubrod performance 0-1 or Karnofsky greater than or equal to 80% for patients > 16 years of age.
  4. Patient or patient's legal representative, parent(s) or guardian able to provide written informed consent.
  5. Patient or patient's legal representative, parent(s) or guardian able to provide written informed consent for the long-term follow-up gene therapy study.
  6. Patient is planning to receive or has received an HLA-identical matched family, related haploidentical donor (</= 7/8 allele match), or at least 8/8 matched unrelated allogeneic HSCT.

Exclusion Criteria:

  1. Patients with known allergy to bovine or murine products.
  2. Active grade 2-4 acute GVHD at time of DLI.
  3. Systemic corticosteroid use within 72 hours of DLI unless required for physiologic replacement.
  4. Less than 80% donor chimerism from peripheral blood within 30 days of DLI administration, if T cells are made from allogeneic donor.
  5. Experiencing any new Grade >2 (CTC version 4) adverse neurologic, pulmonary, cardiac, gastrointestinal, renal or hepatic (excluding albumin) event within 24 hours prior to DLI.
  6. Currently using an investigational agent at time of DLI.
  7. Active infection defined as positive culture, if available, for bacteria, fungus, or virus within a 3-day period prior to DLI and/or fever greater than 38°C within 24 hours prior to DLI.
  8. Positive beta HCG in female of child-bearing potential defined as not post menopausal for 12 months or absence of previous surgical sterilization.
  9. Active CNS disease in patient with history of CNS malignancy.
  10. Positive serology for HIV.
  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 ClinicalTrials.gov identifier: NCT01497184

Contacts
Contact: Partow Kebriaei, MD 713-745-0663

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Partow Kebriaei, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01497184     History of Changes
Other Study ID Numbers: 2009-0525, NCI-2012-00015
Study First Received: December 20, 2011
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Lymphoma
Allogeneic donor lymphocyte infusion
DLI
Hematopoietic Stem Cell Transplantation
HSCT
Bone marrow transplant
CD19-specific T cells
T cell infusion
B-Lineage lymphoid malignancies
CD19+ lymphoid malignancies
Acute lymphoblastic leukemia
ALL
Biphenotypic leukemia CD19+ in advanced remission
Non-Hodgkin's Lymphoma
NHL
Diffuse large B-cell lymphoma
Small lymphocytic lymphoma
Follicular lymphoma
Mantle cell lymphoma with active disease at time of transplant

Additional relevant MeSH terms:
Lymphoma
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on October 19, 2014