CD19-specific T Cell Infusion in Patients With B-Lineage Lymphoid Malignancies
4 other identifiers
interventional
34
1 country
1
Brief Summary
Sometimes researchers change the DNA (genetic material in cells) of donated T cells (white blood cells that support the immune system) using a process called "gene transfer." Gene transfer involves drawing blood from the patient, and then separating out the T-cells using a machine. Researchers then perform a gene transfer to change the T-cells' DNA, and then inject the changed T-cells into the body of the patient. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 lymphoma
Started Jun 2011
Longer than P75 for phase_1 lymphoma
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 28, 2009
CompletedFirst Posted
Study publicly available on registry
August 31, 2009
CompletedStudy Start
First participant enrolled
June 20, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 23, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
April 23, 2020
CompletedDecember 19, 2023
December 1, 2023
8.8 years
August 28, 2009
December 13, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximum Tolerated Dose (MTD) of T-cells ± IL-2
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.
Continuously monitored up to infusions (+14 days) then at 1 day, 3 days, 1 week, and 2 weeks after T cell infusion
Study Arms (2)
CD19-specific T cell Infusion without IL-2
EXPERIMENTALConditioning 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.
CD19-specific T cell Infusion with IL-2
EXPERIMENTALConditioning 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.
Interventions
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.
Stem cell infusion by vein over 30-45 minutes on Day 0
T Cell Infusion (Gene Transfer) by vein over 15-30 minutes sometime between Day +2 through Day +7.
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.
300 mg/m\^2 IV over 1 hour on Day -6
200 mg/m\^2 IV over 3 hours every 12 hours on Days -5 to -2
200 mg/m\^2 by vein over 1 hour every 12 hours on Days -5 to -2.
140 mg/m\^2 IV over 30 minutes on Day -1
Eligibility Criteria
You may qualify if:
- Patients with a history of CD19+ lymphoid malignancies that are beyond first remission or primary refractory to treatment.
- Age 18 to 75 years.
- Zubrod performance 0-1 or Karnofsky greater than or equal to 80%.
- Patient able to provide written informed consent.
- Patient able to provide written informed consent for the long-term follow-up gene therapy study.
- Eligibility at time of transplant conditioning regimen (criteria 6-13): Zubrod performance 0-1 or Karnofsky greater than or equal to 80%.
- Left ventricular ejection fraction \>/= 40%. No uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
- No symptomatic pulmonary disease. FEV1, FVC and DLCO \>/= 50% of expected, corrected for hemoglobin.
- Serum creatinine \</= 1.8mg/dL or creatinine clearance \>/= 40 cc/min.
- 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.
- If positive Hepatitis B and/or Hepatitis C serology, discuss with Principal Investigator or designee and consider liver biopsy.
- No pleural/pericardial effusion or ascites estimated to be \>1L.
- 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.
- Eligibility at time of T-cell infusion (criteria 14-15): No systemic corticosteroids within 3 days prior to T-cell infusion.
- 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.
- +1 more criteria
You may not qualify if:
- Positive beta HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
- Patients with known allergy to bovine or murine products.
- Positive serology for HIV.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
- Alaunos Therapeuticscollaborator
- Intrexon Corporationcollaborator
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Kebriaei P, Singh H, Huls MH, Figliola MJ, Bassett R, Olivares S, Jena B, Dawson MJ, Kumaresan PR, Su S, Maiti S, Dai J, Moriarity B, Forget MA, Senyukov V, Orozco A, Liu T, McCarty J, Jackson RN, Moyes JS, Rondon G, Qazilbash M, Ciurea S, Alousi A, Nieto Y, Rezvani K, Marin D, Popat U, Hosing C, Shpall EJ, Kantarjian H, Keating M, Wierda W, Do KA, Largaespada DA, Lee DA, Hackett PB, Champlin RE, Cooper LJ. Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells. J Clin Invest. 2016 Sep 1;126(9):3363-76. doi: 10.1172/JCI86721. Epub 2016 Aug 2.
PMID: 27482888DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Partow Kebriaei, MD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 28, 2009
First Posted
August 31, 2009
Study Start
June 20, 2011
Primary Completion
April 23, 2020
Study Completion
April 23, 2020
Last Updated
December 19, 2023
Record last verified: 2023-12