Autologous CD19-specific T Cells Infusion

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00968760
First received: August 28, 2009
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

The goal of this clinical research study is to learn if an investigational type of gene transfer can be given reliably and safely in patients with advanced B-cell lymphoma. B cells are a type of white blood cell that fights infection and disease. Lymphoma is a type of cancer that affects the immune system, including B cells.

The gene transfer involves drawing blood, separating out T cells (white blood cells that fight infection and disease), changing the T cells' DNA (genetic material) in a specific way, and returning the changed T cells back to the body.

Researchers want to learn the highest dose of the changed T cells that can be given safely. Researchers also want to learn how long the changed T cells remain in the participant's body, and if the changed T cells can reliably treat B-cell lymphoma. Finally, researchers want to learn if interleukin-2 (IL-2) can help the changed T cells last longer in the body.


Condition Intervention Phase
Lymphoma
B-cell Lymphoma
Procedure: Leukapheresis
Procedure: Stem Cell Transplant
Procedure: CD19-specific T Cell Infusion
Drug: IL-2
Drug: Carmustine
Drug: Etoposide
Drug: Cytarabine
Drug: Melphalan
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 Autologous 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 T-cells ± IL-2 [ Time Frame: Continuously monitored up to infusions (+14 days) then at 1 day, 3 days, 1 week, and 2 weeks after T cell infusion ] [ Designated as safety issue: Yes ]

    The MTD is the highest dose at which at least 6 participants treated with the proportion of participants having dose limiting toxicities (DLT) < 1/3.

    DLT is defined as a new adverse event of grade >3 involving cardiopulmonary, gastrointestinal, hepatic (excluding albumin), neurological, or renal Common Terminology Criteria for Adverse Events (CTCAE) version 4 parameters that is probably or definitely related to the infused T-cell product.



Estimated Enrollment: 60
Study Start Date: June 2011
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CD19-specific T cell Infusion without IL-2

Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer

Group 1 - low dose of T cells without IL-2.

Group 3 - higher dose of T cells without IL-2.

Procedure: Leukapheresis

Leukapheresis #1 - For Collecting T Cells

Leukapheresis #2 - For Collecting Stem Cells, month following #1

Blood drawn through vein, passed through a machine to collect specific blood cells, then remaining blood returned, about 3 hours to complete.

Procedure: Stem Cell Transplant
Stem cell infusion by vein over 30-45 minutes on Day 0
Other Name: SCT
Procedure: CD19-specific T Cell Infusion
T Cell Infusion (Gene Transfer) by vein over 15-30 minutes sometime between Day +2 through Day +7.
Drug: Carmustine
300 mg/m^2 IV over 1 hour on Day -6
Other Names:
  • BCNU
  • BiCNU
Drug: Etoposide
200 mg/m^2 IV over 3 hours every 12 hours on Days -5 to -2
Other Name: VePesid
Drug: Cytarabine
200 mg/m^2 by vein over 1 hour every 12 hours on Days -5 to -2.
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride
Drug: Melphalan
140 mg/m^2 IV over 30 minutes on Day -1
Other Name: Alkeran
Experimental: CD19-specific T cell Infusion with IL-2

Conditioning Regimen of Chemotherapy (Carmustine, Cytarabine, Etoposide, and Melphalan), Stem Cell Transplant, and Gene Transfer

Group 2 - higher dose of T cells with IL-2.

Group 4 - higher dose of T cells with IL-2.

Procedure: Leukapheresis

Leukapheresis #1 - For Collecting T Cells

Leukapheresis #2 - For Collecting Stem Cells, month following #1

Blood drawn through vein, passed through a machine to collect specific blood cells, then remaining blood returned, about 3 hours to complete.

Procedure: Stem Cell Transplant
Stem cell infusion by vein over 30-45 minutes on Day 0
Other Name: SCT
Procedure: CD19-specific T Cell Infusion
T Cell Infusion (Gene Transfer) by vein over 15-30 minutes sometime between Day +2 through Day +7.
Drug: IL-2
Group 2 or 4, IL-2 dose of 0.3 x 10^6 U/m^2 injected under skin, once a day for up to 14 days; first dose on day of T cell infusion.
Other Names:
  • Interleukin-2
  • Proleukin
Drug: Carmustine
300 mg/m^2 IV over 1 hour on Day -6
Other Names:
  • BCNU
  • BiCNU
Drug: Etoposide
200 mg/m^2 IV over 3 hours every 12 hours on Days -5 to -2
Other Name: VePesid
Drug: Cytarabine
200 mg/m^2 by vein over 1 hour every 12 hours on Days -5 to -2.
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride
Drug: Melphalan
140 mg/m^2 IV over 30 minutes on Day -1
Other Name: Alkeran

  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 beyond first remission or primary refractory to treatment.
  2. Age 1 to 65 years.
  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. Eligibility at time of transplant conditioning regimen (criteria 6-13): Zubrod performance 0-2 or Karnofsky of 50% to 100%.
  7. Left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
  8. No symptomatic pulmonary disease. FEV1, FVC and DLCO >/= 50% of expected, corrected for hemoglobin.
  9. Serum creatinine </= 1.8mg/dL or creatinine clearance >/= 40 cc/min.
  10. Adequate hepatic function, as defined by SGPT <3 X upper limit of normal; serum bilirubin and alkaline phosphatase <2 X upper limit of normal, or considered not clinically significant.
  11. If positive Hepatitis B and/or Hepatitis C serology, discuss with Principal Investigator or designee and consider liver biopsy.
  12. No pleural/pericardial effusion or ascites estimated to be >1L.
  13. Not breast feeding or pregnant. Pregnancy determined by a positive beta HCG test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization.
  14. Eligibility at time of T-cell infusion (criteria 14-15): No systemic corticosteroids within 3 days prior to T-cell infusion.
  15. Not experiencing any new Grade >2 (CTC version 4) adverse neurologic, pulmonary, cardiac, gastrointestinal, renal or hepatic (excluding albumin) event within 24 hours prior to T-cell infusion.
  16. Eligibility criteria for administration of IL-2 after T-cell infusion: Absence of new adverse event of grade >2 (CTC vs. 4) involving cardiopulmonary, hepatic (excluding albumin), gastrointestinal, neurologic, or renal toxicity probably or definitely attributed to infused T cells within one week of cells.

Exclusion Criteria:

  1. Positive beta HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
  2. Patients with known allergy to bovine or murine products.
  3. 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: NCT00968760

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

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

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00968760     History of Changes
Other Study ID Numbers: 2007-0635, 5R01CA141303-03, NCI-2011-01129
Study First Received: August 28, 2009
Last Updated: September 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
CD19+ lymphoid malignancies
non-Hodgkin's Lymphoma
NHL
small lymphocytic lymphoma
SLL
follicular lymphoma
mantle cell lymphoma
gene cell transfer
CD19-specific T cells
Stem Cell Transplant
T Cell Infusion
Chemotherapy
Leukapheresis
BCNU
carmustine
Cytarabine
Etoposide
Interleukin-2
Proleukin
Melphalan
Rituximab
T cell therapy

Additional relevant MeSH terms:
Lymphoma, B-Cell
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Etoposide
Etoposide phosphate
Cytarabine
Melphalan
Interleukin-2
Carmustine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 01, 2014