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

NCT03081910 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: H-40466, MAGENTAP50CA126752
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

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

Keywords

Autologous CAR T cells; T-cell acute lymphoblastic lymphoma; T-non-Hodgkin Lymphoma; T-cell Acute Lymphoblastic Leukemia; Allogeneic CAR T cells

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT) rate

  Defined as the proportion of subjects in each group with DLT evaluated as per the CTCAE 4.0 with the exception of Cytokine Release Syndrome (CRS) and neurological toxicities that are related to T cell infusions.

  6 weeks post-infusion

Secondary Outcomes (1)

• Overall Response Rate

  4 weeks pre-infusion and 6 weeks post-infusion

Study Arms (2)

Autologous CD5.CAR/28zeta CAR T cells (Group A) - NOW CLOSED

EXPERIMENTAL

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.

Genetic: Autologous CD5.CAR/28zeta CAR T cells

Allogeneic CD5.CAR/28zeta CAR T cells (Group B)

EXPERIMENTAL

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.

Genetic: Allogeneic CD5.CAR/28zeta CAR T cells

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

Autologous CD5.CAR/28zeta CAR T cells (Group A) - NOW CLOSED

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

Allogeneic CD5.CAR/28zeta CAR T cells (Group B)

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Referred patients (Group A - NOW CLOSED) or their previous HSCT donors (Group B) will initially be consented for procurement of blood for generation of the transduced ATL. Patient eligibility criteria at this stage include:
• Diagnosis of recurrent T-cell acute lymphoblastic leukemia (T-ALL), T-cell acute lymphoblastic lymphoma (T-LLy), or T-non-Hodgkin lymphoma (T-NHL, including Angioimmunoblastic T-cell lymphoma (AITL), Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), Peripheral T-cell lymphoma (PTCL) NOS, Anaplastic large cell lymphoma (ALCL), Adult T-cell leukemia/lymphoma, T cell prolymphocytic leukemia with symptomatic disease, Extranodal NK/T cell lymphoma, Mycosis fungoides/ Sezary Syndrome Stage IIB or higher))
• AND
• Group A (auto arm - NOW CLOSED): Transplant naïve or relapsed post-allogeneic HSCT OR
• Group B (allo arm): Relapsed post-allogeneic HSCT with previous HSCT donor from whom allogeneic MAGENTA CAR T cells can be manufactured
• AND
• Suitable for allogeneic hematopoietic stem cell transplant (HSCT) with confirmation of an identified eligible allo-HSCT donor by FACT accredited institution
• Confirmation that the center plans to proceed with transplant if CD5.CAR treatment induces a complete remission.
• For T-NHL subjects, eligibility will be confined to disease stages where allogeneic HSCT is indicated.
• CD5-positive tumor (result can be pending at this time). \> 50% CD5 + blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory.
• Age ≤75 years old. NOTE: The first six (6) patients treated on the study should be adults (\>18 yrs of age).
• Life expectancy of greater than 12 weeks.
• Patients must have an available partially-HLA matched allogeneic EBV-specific T cell line on a BCM IRB approved protocol which can be used as treatment in the event of uncontrolled EBV reactivation
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
• Hgb greather than or equal to 7.0 g/dL (can be transfused)

You may not qualify if:

• Active infection requiring antibiotics.
• Active infection with HIV
• History of other cancer (except non-melanoma skin cancer or in situ breast cancer or cervix cancer) unless the tumor was successfully treated with curative intent at least 2 years before trial entry.
• Donor must be prior hematopoietic stem cell transplant donor for patients relapsed post-allogeneic HSCT. Prior transplant donors will be screened with the standard blood bank donor questionnaire, medical history, and testing for infectious disease markers (IDMs; which may be pending at the time of blood collection). Medical history may be obtained by the patient's primary/referring transplant team if collection is being done remotely. The physician assessment, donor questionnaire, and IDMs will be reviewed by the principle investigator or appropriate designee to confirm/provide final eligibility determination and documented in the donor's medical record.
• Informed consent explained to, understood by and signed by donor/LAR. Donor/LAR given copy of informed consent.
• Patients must meet the following eligibility criteria to be included for treatment:
• Diagnosis of recurrent T-cell acute lymphoblastic leukemia (T-ALL), T-cell acute lymphoblastic lymphoma (T-LLy), or T-non-Hodgkin lymphoma (T-NHL, including Angioimmunoblastic T-cell lymphoma (AITL), Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), Peripheral T-cell lymphoma (PTCL) NOS, Anaplastic large cell lymphoma (ALCL), Adult T-cell leukemia/lymphoma, T cell prolymphocytic leukemia with symptomatic disease, Extranodal NK/T cell lymphoma, Mycosis fungoides/ Sezary Syndrome Stage IIB or higher))
• AND
• Group A (auto arm - NOW CLOSED): Transplant naïve or relapsed post-allogeneic HSCT OR
• Group B (allo arm): Relapsed post-allogeneic HSCT with previous HSCT donor from whom allogeneic MAGENTA CAR T cells can be manufactured
• AND
• Suitable for allogeneic hematopoietic stem cell transplant (HSCT) with confirmation of an identified eligible allo-HSCT donor by FACT accredited institution
• Confirmation that the center plans to proceed with transplant if CD5.CAR treatment induces a complete remission.
• For T-NHL subjects, eligibility will be confined to disease stages where allogeneic HSCT is indicated.
• CD5-positive tumor. \>50% CD5 + blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

• Dai Z, Mu W, Zhao Y, Jia X, Liu J, Wei Q, Tan T, Zhou J. The rational development of CD5-targeting biepitopic CARs with fully human heavy-chain-only antigen recognition domains. Mol Ther. 2021 Sep 1;29(9):2707-2722. doi: 10.1016/j.ymthe.2021.07.001. Epub 2021 Jul 16.

  PMID: 34274536 DERIVED

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Rayne Rouce, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rayne Rouce, MD

CONTACT

832-824-4716; rhrouce@texaschildrens.org

Martha Arredondo

CONTACT

832-824-1201; mearredo@texaschildrens.org

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: Assistant Professor

Study Record Dates

• First Submitted: March 8, 2017
• First Posted: March 16, 2017
• Study Start: November 1, 2017
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): September 1, 2040
• Last Updated: September 4, 2025

Record last verified: 2025-08

Locations

US (2)