Multi-virus CTLs Expressing CD19 Chimeric Receptors, CD19 Positive Malignancies Post SCT, MULTIPRAT
MULTIPRAT
Phase I Study of the Administration of Multi-Virus-Specific Cytotoxic T Lymphocytes Expressing CD19 Chimeric Receptors for Prophylaxis or Therapy of Relapse of CD19 Positive Malignancies Post Hematopoietic Stem Cell Transplantation
2 other identifiers
interventional
68
1 country
2
Brief Summary
Subjects are having a bone marrow or SCT for either a type of cancer of the blood called Leukemia or a cancer of the lymph nodes called non- Hodgkin's Lymphoma. Although a transplant can cure leukemia or lymphoma, some people will relapse. In those who relapse, current treatment cures only a very small percentage. Although giving patients a dose of donor immune cells before relapse can prevent relapse of the leukemia or lymphoma, DLI can also cause a serious complication called graft versus host disease (GVHD). This is a gene transfer research study using special immune cells which are specific for these cancer cells. The body has different ways of fighting infection and disease. This study combines 2 of those ways, antibodies and T cells. T cells (CTLs or cytotoxic T cells) are infection-fighting blood cells that can kill cells, including tumor cells. Antibodies and T cells have been used to treat patients with cancers; they have shown promise, but haven't been strong enough to cure most patients. The antibody used in this study is called anti-CD19. This antibody sticks to leukemia cells because of a substance on the outside of these cells called CD19. For this study, the anti-CD19 antibody has been changed so that instead of floating free in the blood it is now joined to T cells. When an antibody is joined to a T cell in this way it's called a chimeric receptor. In the laboratory, investigators found that T cells that are trained to recognize common viruses can stay in the blood stream for many years. By joining the anti-CD19 antibody to CTLs that recognize viruses, they believe that they will also be able to make a cell that can last a long time in the body, provide protection from viruses, and recognize and kill leukemia. The CTLs which we will join the anti-CD19 antibody to attack 3 viruses (trivirus-specific CTLs), CMV, EBV, and adenovirus. Studies have shown that trivirus-specific CTLs grown from the stem cell donor can be given safely to transplant recipients and can stop these viruses from causing severe infections. These CD19 chimeric receptor trivirus specific T cells are an investigational product not approved by the FDA. The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to assess the side effects, to see how long the T cells last and to evaluate whether this therapy might help prevent infections and relapse in people with CD19+ leukemia or lymphoma having a SCT.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2009
Longer than P75 for phase_1
2 active sites
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
February 9, 2009
CompletedFirst Posted
Study publicly available on registry
February 10, 2009
CompletedStudy Start
First participant enrolled
April 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2031
ExpectedJuly 9, 2025
July 1, 2025
7 years
February 9, 2009
July 4, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of dose limiting toxicities
Dose limiting toxicity (DLT) is defined as development of grade III-IV GVHD or NCI CTC grade 3-5 toxicity that is not preexisting and/or not due to the underlying malignancy or infection or treatment of relapse within 30 days of study drug administration. DLTs will be graded according to NCI CTCAE v3.0.
6 weeks
Secondary Outcomes (3)
Tumor response to gene modified CTL on measurable disease.
up to 15 years
Frequency of T-cells expressing gene-modified CTLs.
up to 15 years
Frequency of CD19+ B-Cells post HSCT expressing gene-modified CTLs
up to 15 years
Study Arms (4)
Group A with disease
EXPERIMENTALCD19+ B-ALL undergoing allogeneic HSCT, with minimal residual disease or relapse post-HSCT Patients will receive one of the following dose levels of CD19CAR/virus specific T cells: Dose Level 1: 1.5 x 10\^7/m2 Dose Level 2: 4.5 x 10\^7/m2 Dose Level 3: 1.2 x 10\^8/m2 Patients will be evaluated in the clinic and a single dose of CTL will be administered from day +30 post-HSCT. Patients may be premedicated with Benadryl and Tylenol before receiving the injection of cells. If patients with relapse have a partial response or have stable disease they will be eligible to receive up to 6 further doses of CTLs, each of which will consist of the same number or less than as their first injection.
Group A without disease
EXPERIMENTALCD19+ B-ALL undergoing allogeneic HSCT, without detectable disease post-HSCT. Patients will receive CD19CAR/virus specific T cells - Dose Level 1: 1.5 x 10\^7/m2 Patients will be evaluated in the clinic and a single dose of CTL will be administered from day +30 post-HSCT. Patients may be premedicated with Benadryl and Tylenol before receiving the injection of cells.
Group B with disease
EXPERIMENTALCD19+ B cell CLL or NHL undergoing allogeneic HSCT, with minimal residual disease or relapse post-HSCT Patients will receive one of the following dose levels of CD19CAR/virus specific T cells: Dose Level 1: 1.5 x 10\^7/m2 Dose Level 2: 4.5 x 10\^7/m2 Dose Level 3: 1.2 x 10\^8/m2 Patients will be evaluated in the clinic and a single dose of CTL will be administered from day +30 post-HSCT. Patients may be premedicated with Benadryl and Tylenol before receiving the injection of cells. If patients with relapse have a partial response or have stable disease they will be eligible to receive up to 6 further doses of CTLs, each of which will consist of the same number or less than as their first injection.
Group B without disease
EXPERIMENTALCD19+ B cell CLL or NHL undergoing allogeneic HSCT, without detectable disease post-HSCT Patients will receive CD19CAR/virus specific T cells - Dose Level 1: 1.5 x 10\^7/m2 Patients will be evaluated in the clinic and a single dose of CTL will be administered from day +30 post-HSCT. Patients may be premedicated with Benadryl and Tylenol before receiving the injection of cells.
Interventions
CD19CAR/virus specific T cells will be thawed and given by intravenous injection from day +30 post transplant.
Patients may be premedicated with Benadryl and Tylenol before receiving the injection of cells.
Eligibility Criteria
You may qualify if:
- Any patient regardless of sex or age with CD19+ B-ALL undergoing allogeneic HSCT (Group A)
- OR Any patient regardless of sex or age with CD19+ B-CLL or NHL undergoing allogeneic HSCT (Group B).
- AND
- With minimal residual disease (MRD) or relapse post-HSCT (for the phase I dose escalation)
- With no evidence of ALL or CLL/NHL post-HSCT (to be included in the expansion cohort
- Patients with life expectancy greater than or equal to 6 weeks
- Patients with a Karnofsky/Lansky score greater than or equal to 50
- Donor HIV negative
- Patient or parent/guardian capable of providing informed consent
- Patients with bilirubin 2x normal or less, AST 3x normal or less, creatinine less than or equal to 2x normal for age and Hgb greater than 8.0
- Pulse oximetry of greater than 90% on room air
- Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the CTL infusion. The male partner should use a condom.
- Available allogeneic CD19CAR transduced tri-virus-specific cytotoxic T lymphocytes with greater than or equal to15% expression of CD19CAR determined by flow-cytometry and greater than 10% killing of one or more viral antigen pulsed targets in a cytotoxicity assay at an effector:target ratio of 20:1.\*
- Patients should have been off other investigational antiviral or antitumor therapy for one month prior to entry in this study.
- Note: Cell dose is based on total cell numbers and not individual antivirus or antileukemic cell numbers.
You may not qualify if:
- Severe intercurrent infection
- Evidence of graft versus host disease \>grade II
- Pregnant or lactating
- History of hypersensitivity reactions to murine protein-containing products.
- Currently taking corticosteroids for therapy of GVHD.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Houston Methodist Hospital
Houston, Texas, 77030, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Related Publications (2)
Sun J, Huye LE, Lapteva N, Mamonkin M, Hiregange M, Ballard B, Dakhova O, Raghavan D, Durett AG, Perna SK, Omer B, Rollins LA, Leen AM, Vera JF, Dotti G, Gee AP, Brenner MK, Myers DG, Rooney CM. Early transduction produces highly functional chimeric antigen receptor-modified virus-specific T-cells with central memory markers: a Production Assistant for Cell Therapy (PACT) translational application. J Immunother Cancer. 2015 Feb 18;3:5. doi: 10.1186/s40425-015-0049-1. eCollection 2015.
PMID: 25734008DERIVEDCruz CR, Micklethwaite KP, Savoldo B, Ramos CA, Lam S, Ku S, Diouf O, Liu E, Barrett AJ, Ito S, Shpall EJ, Krance RA, Kamble RT, Carrum G, Hosing CM, Gee AP, Mei Z, Grilley BJ, Heslop HE, Rooney CM, Brenner MK, Bollard CM, Dotti G. Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study. Blood. 2013 Oct 24;122(17):2965-73. doi: 10.1182/blood-2013-06-506741. Epub 2013 Sep 12.
PMID: 24030379DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Carlos A Ramos, MD
Baylor College of Medicine
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
February 9, 2009
First Posted
February 10, 2009
Study Start
April 1, 2009
Primary Completion
April 1, 2016
Study Completion (Estimated)
April 1, 2031
Last Updated
July 9, 2025
Record last verified: 2025-07