Activated T Lymphocytes Expressing CARs, Relapsed CD19+ Malignancies Post-Allo HSCT(CARPASCIO)
CARPASCIO
Phase I Study of Activated T Lymphocytes Expressing Chimeric Antigen Receptors for Therapy of Relapsed CD19-Positive Malignancies Post-Allogeneic Hematopoietic Stem Cell Transplantation Infused Only After Engraftment (CARPASCIO)
2 other identifiers
interventional
7
1 country
2
Brief Summary
Patients have a type of lymph gland cancer called Non-Hodgkin Lymphoma (NHL), acute lymphocytic leukemia (ALL) or chronic lymphocytic leukemia (CLL) (these diseases will be referred to as "lymphoma" or "leukemia"). The lymphoma or leukemia has come back or has not gone away after treatment (including the best treatment known for these cancers). Because there is no standard treatment for this cancer at this time, subjects are asked to volunteer to be in a gene transfer research study using special immune cells. The body has different ways of fighting infection and disease. No one way seems perfect for fighting cancers. This research study combines two different ways of fighting disease, antibodies and T cells, hoping that they will work together. Both antibodies and T cells have been used to treat patients with cancers; they have shown promise, but have not been strong enough to cure most patients. T cells can kill tumor cells but there normally are not enough of them to kill all the tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person. The antibody used in this study is called anti-CD19. This antibody sticks to cancer cells because of a substance on the outside of these cells called CD19. CD19 antibodies have been used to treat people with lymphoma and leukemia. For this study, the CD19 antibody has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. The T lymphocytes will also contain CD28, which stimulates T cells and makes them last longer. Treatment with CD19/CD28 chimeric receptor-T cells has had activity against lymphoma and leukemia when the cells are made from the patients affected by these diseases. In this study, investigators are going to see if this treatment works even better when they make these cells from a healthy stem cell donor. If investigators are not able to collect blood from the stem cell donor, they will collect blood from the subject to make the CD19/CD28 chimeric receptor-T cells. These CD19/CD28 chimeric receptor T cells are investigational products not approved by the FDA. The purpose of this study is to find the biggest dose of chimeric T Cells that is safe, to see how long T cells with this chimeric receptor last, to learn what the side effects are, and to see whether this therapy might help people with lymphoma or leukemia after a stem cell transplantation from a donor.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Apr 2014
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
January 29, 2014
CompletedFirst Posted
Study publicly available on registry
January 30, 2014
CompletedStudy Start
First participant enrolled
April 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2030
ExpectedNovember 14, 2025
November 1, 2025
5.5 years
January 29, 2014
November 12, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of patients with dose limiting toxicity
Toxicity is evaluated using CTCAE, version 4.0. Dose limiting toxicity (DLT) will be defined as any of the following that is NOT (1) pre-existing, or (2) due to infection (to which patients with CLL and NHL are predisposed), or (3) due to underlying malignancy, and that may, after consultation with the FDA when indicated, be considered possibly, probably, or definitely related to the study cellular products: * Development of Grade III-IV GVHD or Grade II GVHD unresponsive to front line treatment; * Non-hematologic DLT is any grade 3 or grade 4 non-hematologic toxicity, including allergic reactions to T cell infusions. * Hematologic DLT is defined as any grade 4 hematologic toxicity, including secondary graft failure (as defined per protocol). * Patients with evidence of bone marrow disease (metastases or diffuse infiltration) are not evaluable for hematologic dose limiting toxicity.
6 weeks
Secondary Outcomes (2)
Number of patients with tumor response
8 weeks
Frequency of T cell products
Up to 15 years
Study Arms (4)
Subgroup A1
EXPERIMENTALPatients with residual or relapsed B-cell ALL and with an HLA-matched related donor will receive CD19.CAR-CD28Z T Cells - dose escalation 1
Subgroup B1
EXPERIMENTALPatients with other B-cell malignancies and with an HLA-matched related donor will receive CD19.CAR-CD28Z T Cells - dose escalation 1
Subgroup A2
EXPERIMENTALPatients with residual or relapsed B-cell ALL and with an unrelated or HLA-mismatched donor will receive CD19.CAR-CD28Z T Cells - dose escalation 2
Subgroup B2
EXPERIMENTALPatients with other B cell malignancies and with an unrelated or HLA-mismatched donor will receive CD19.CAR-CD28Z T Cells - dose escalation 2
Interventions
Patients will receive one of the following dose levels: Dose Level 1: 5 ×10\^5 cells/kg Dose Level 2: 1×10\^6 cells/kg Dose Level 3: 5×10\^6 cells/kg
Patients will receive one of the following doses: Dose Level one: 1x10\^5 cells/kg Dose Level 2: 5x10\^5 cells/kg Dose Level 3: 1x10\^6 cells/kg
Eligibility Criteria
You may qualify if:
- PROCUREMENT
- Group A: CD19+ B-ALL undergoing allogeneic HSCT or Group B: CD19+ B cell CLL or NHL undergoing allogeneic HSCT
- Life expectancy of ≥12 weeks.
- Patient has an appropriate donor identified for hematopoietic stem cell transplantation
- TREATMENT
- 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)
- Residual disease at the time of transplant (bulky or minimal) or post transplant relapse as evidenced by PCR positivity, specific cytogenetic abnormalities, an abnormal population on flow cytometry or increased blasts on bone marrow biopsy or in the peripheral blood. MRD will be defined as detection in blood or marrow of any of the following:
- Any leukemia specific marker (such as t(9:22) or t(4:11)) documented in the patient's leukemia cells pre transplant on a post transplant evaluation.
- An immune globulin rearrangement known to be a disease marker for this patient post transplant.
- A leukemia specific phenotype post transplant at a level of ≥ 0.01%
- Mixed donor chimerism (any level)
- Life expectancy ≥ 6 weeks
- Karnofsky/Lansky score ≥ 50%.
- Bilirubin ≤ 2 times the upper limit of normal.
- AST ≤ 3 times the upper limit of normal.
- +7 more criteria
You may not qualify if:
- Severe intercurrent infection.
- Evidence of GVHD \> grade II.
- Pregnant or lactating.
- History of hypersensitivity reactions to murine protein-containing products.
- Currently taking corticosteroids (\>0.5 mg/kg/day prednisone or equivalent) 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
MeSH Terms
Conditions
Condition 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
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor
Study Record Dates
First Submitted
January 29, 2014
First Posted
January 30, 2014
Study Start
April 1, 2014
Primary Completion
October 1, 2019
Study Completion (Estimated)
December 1, 2030
Last Updated
November 14, 2025
Record last verified: 2025-11