Autologous T-Cells Expressing a Second Generation CAR for Treatment of T-Cell Malignancies Expressing CD5 Antigen

Part of paid clinical trials in Houston, Texas.

Sponsor
Baylor College of Medicine
Study ID
NCT03081910
Phase
PHASE1
Status
Recruiting
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Conditions

  • T-cell Acute Lymphoblastic Leukemia
  • T-cell Acute Lymphoblastic Lymphoma
  • T-non-Hodgkin Lymphoma

Eligibility Criteria

Sex
ALL
Age
N/A - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Autologous CD5.CAR/28zeta CAR T cells — GENETIC
    Three dose levels will be evaluated: Dose level one: 1×10\^7 cells/m2 Dose level two: 5×10\^7 cells/m2 Dose level three: 1×10\^8 cells/m2
  • Allogeneic CD5.CAR/28zeta CAR T cells — GENETIC
    Three dose levels will be evaluated: Dose level one: 1×10\^7 cells/m2 Dose level two: 5×10\^7 cells/m2 Dose level three: 1×10\^8 cells/m2

Study Details

Patients eligible for this study have a type of blood cancer called T-cell leukemia or lymphoma (lymph gland cancer). The body has different ways of fighting infection and disease. No one way seems perfect for fighting cancers. This research combines two different ways of fighting disease, antibodies and T cells. Antibodies are proteins that protect the body from bacterial and other diseases. T cells, or T lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. Both antibodies and T cells have shown promise treating patients with cancers, but have not been strong enough to cure most patients. T lymphocytes can kill tumor cells but there normally are not enough of them. Some researchers have taken T cells from a person's blood, grown more in the lab then given them back to the person. In some patients who've had recent bone marrow or stem cell transplant, the number of T cells in their blood may not be enough to grow in the lab. In this case, T cells may be collected from their previous transplant donor, who has a similar tissue type. The antibody used in this study, called anti-CD5, first came from mice that have developed immunity to human leukemia. This antibody sticks to T-cell leukemia or lymphoma cells because of a substance on the outside of these cells called CD5. CD5 antibodies have been used to treat people with T-cell leukemia and lymphoma. For this study, anti-CD5 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. In the lab, investigators have also found that T cells work better if stimulating proteins, such as one called CD28, are also added. Adding the CD28 makes the cells grow better and last longer in the body, giving them a better chance of killing the leukemia or lymphoma cells. In this study investigators will attach the CD5 chimeric receptor with CD28 added to it to the patient's T cells or the previous bone marrow transplant donor's T cells. The investigators will then test how long the cells last. The decision to use the bone marrow transplant donor's T cells instead of the patient's will be based on 1) whether there is an available and willing donor and 2) the likelihood of the patient's T cells being able to grow in the lab. These CD5 chimeric receptor T cells with CD28 are investigational products not approved by the FDA. UPDATE: Please note that the Autologous Arm of this study is now closed.

Key Dates

Start date
Nov 1, 2017
Status verified
Aug 2025
Primary completion
Jun 1, 2028
Completion
Sep 1, 2040

Study Design

Enrollment
54 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Autologous CD5.CAR/28zeta CAR T cells (Group A) - NOW CLOSED
    Three dose levels will be evaluated. The T cells will be administered with Cytoxan and fludarabine.If patients have experienced either a partial response or stable disease and completed the 6 week toxicity evaluation without evidence of DLT or other infectious complications, they will be eligible to receive up to 3 additional infusions of CD5 CAR.T cells. Patients remain eligible for up to 3 additional infusions as long as they continue to have a clinical response and absence of safety concerns. If patients experience a complete response following an additional infusion, investigators will recommend they proceed to allogeneic HSCT. Once dose escalation is completed, the trial will be expanded and treat up to an additional 6 patients (2 cohorts) at the MTD in each group to gather additional safety data and preliminary efficacy data.
  • Experimental: Allogeneic CD5.CAR/28zeta CAR T cells (Group B)
    Three dose levels will be evaluated. The T cells will be administered with Cytoxan and fludarabine.If patients have experienced either a partial response or stable disease and completed the 6 week toxicity evaluation without evidence of DLT or other infectious complications, they will be eligible to receive up to 3 additional infusions of CD5 CAR.T cells. Patients remain eligible for up to 3 additional infusions as long as they continue to have a clinical response and absence of safety concerns. If patients experience a complete response following an additional infusion, investigators will recommend they proceed to allogeneic HSCT. Once dose escalation is completed, the trial will be expanded and treat up to an additional 6 patients (2 cohorts) at the MTD in each group to gather additional safety data and preliminary efficacy data.

Primary Outcome Measure

Dose limiting toxicity (DLT) rate [ Time Frame: 6 weeks post-infusion ]

Central Contacts

Locations (2)

FacilityCityStateZIPSite coordinators
Houston Methodist HospitalHoustonTexas77030
Rayne Rouce, MD
[email protected]
832-824-4716
Texas Children's HospitalHoustonTexas77030
Rayne Rouce, MD
[email protected]
832-824-4716

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