Cell Therapy for High Risk T-Cell Malignancies Using CD7-Specific CAR Expressed On Autologous T Cells

NCT03690011 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: H-43761 - CRIMSON NE
• Study Type: interventional
• Target: 27
• 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. This study combines two different ways of fighting disease with antibodies and T cells. Antibodies are types of 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 been used to treat cancer; 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-CD7. This antibody sticks to T-cell leukemia or lymphoma cells because of a substance on the outside of these cells called CD7. CD7 antibodies have been used to treat people with T-cell leukemia and lymphoma. For this study, anti-CD7 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 laboratory, investigators have also found that T cells work better if they also add proteins that stimulate T cells, such as one called CD28. Adding the CD28 makes the cells grow better and last longer in the body, thus giving the cells a better chance of killing the leukemia or lymphoma cells. In this study, investigators attach the CD7 chimeric receptor with CD28 added to it to T cells. Investigators will then test how long the cells last. These CD7 chimeric receptor T cells with CD28 are investigational products not approved by the Food and Drug Administration.

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

Outcome Measures

Primary Outcomes (1)

• Number of patients with dose limiting toxicity

  To evaluate the safety of escalating doses of autologous peripheral blood T lymphocytes (ATLs) genetically modified to express chimeric antigen receptors (CAR) targeting the CD7 molecule (CD7.CAR) in combination with lymphodepletion in patients with relapsed/refractory T-cell malignancies.

  4 weeks

Secondary Outcomes (1)

• Overall Response Rate

  4 weeks

Study Arms (1)

CD7.CAR/28zeta CAR T Cells

EXPERIMENTAL

Four dose levels will be evaluated. The T cells will be administered following lymphodepleting chemotherapy with cyclophosphamide and fludarabine.

Genetic: CD7.CAR/28zeta CAR T cells

Interventions

CD7.CAR/28zeta CAR T cells GENETIC

Three dose levels will be evaluated: * Dose level one: 1×10\^7 cells/m\^2 * Dose level two: 3×10\^7 cells/m\^2 * Dose level three: 5x10\^7 cells/m\^2 * Dose level four: 1×10\^8 cells/m\^2

CD7.CAR/28zeta CAR T Cells

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 will initially be consented for procurement of blood for generation of the transduced ATL. Eligibility criteria at this stage include:
• \. Diagnosis of recurrent or refractory 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) or other cutaneous T-cell lymphomas
• AND
• suitable for allogeneic hematopoietic stem cell transplant (HSCT)
• with a suitable donor identified by a FACT accredited transplant center
• willing to proceed to transplant if the CD7.CAR treatment induces complete remission and the patient/donor remain suitable candidates
• Using NMDP donor assessment criteria, suitability is defined as "during the search process, a donor is medically fit to proceed to the next step- whether high-resolution or confirmatory HLA testing OR donor work-up." Documentation of suitability (including above criteria) will be confirmed by the investigator prior to treatment.
• For T-NHL subjects, eligibility will be confined to disease stages where allogeneic HSCT is indicated.
• \. CD7-positive tumor (≥20% CD7 positive blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory).
• \. Age \</=75 years old.. NOTE: The first three (3) patients treated on the study must be adults (\>/=18 yrs of age).
• \. Hgb ≥ 7.0 (can be transfused)
• \. Life expectancy greater than 12 weeks
• \. If pheresis required to collect blood:
• Cr \< 1.5 upper limit normal
• AST \< 5 × upper limit normal

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.
• \. Diagnosis of recurrent or refractory 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) or other cutaneous T-cell lymphomas
• AND
• \) suitable for allogeneic hematopoietic stem cell transplant (HSCT) 2) with a suitable donor identified by a FACT accredited transplant center 3) willing to proceed to transplant if the CD7.CAR treatment induces complete remission and the patient/donor remain suitable candidates
• Using NMDP donor assessment criteria, suitability is defined as "during the search process, a donor is medically fit to proceed to the next step- whether high-resolution or confirmatory HLA testing OR donor work-up." Documentation of suitability (including above criteria) will be confirmed by the investigator prior to treatment.
• For T-NHL subjects, eligibility will be confined to disease stages where allogeneic HSCT is indicated.
• \. CD7-positive tumor (≥20% CD7+ blasts by flow cytometry or immunohistochemistry (tissue) assessed in a CLIA certified Flow Cytometry/Pathology laboratory.
• \. Age \</=75 years old. NOTE: The first three (3) patients treated on the study must be adults (\>/=18 yrs of age).
• \. Bilirubin less than 3 times the upper limit of normal.
• \. AST less than 5 times the upper limit of normal.
• \. Estimated GFR ≥ 50 mL/min.
• \. Pulse oximetry of \> 90% on room air
• \. Karnofsky or Lansky score of ≥ 60.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Leukemia and Lymphoma Society: collaborator
• Cancer Prevention Research Institute of Texas: 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 (2)

• Velasquez MP. Allogeneic CD7-CAR T cells to bridge the gap? Transplant Cell Ther. 2023 Mar;29(3):139-140. doi: 10.1016/j.jtct.2023.02.006. No abstract available.

  PMID: 36858787 DERIVED

• Watanabe N, Mo F, Zheng R, Ma R, Bray VC, van Leeuwen DG, Sritabal-Ramirez J, Hu H, Wang S, Mehta B, Srinivasan M, Scherer LD, Zhang H, Thakkar SG, Hill LC, Heslop HE, Cheng C, Brenner MK, Mamonkin M. Feasibility and preclinical efficacy of CD7-unedited CD7 CAR T cells for T cell malignancies. Mol Ther. 2023 Jan 4;31(1):24-34. doi: 10.1016/j.ymthe.2022.09.003. Epub 2022 Sep 9.

  PMID: 36086817 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

  Pediatrics, Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• LaQuisa Hill, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

LaQuisa Hill, MD

CONTACT

713-441-1450; LaQuisa.Hill@bcm.edu

Martha Arredondo

CONTACT

832-824-1201; Martha.Arredondo@bcm.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 20, 2018
• First Posted: October 1, 2018
• Study Start: August 2, 2021
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2040
• Last Updated: October 23, 2025

Record last verified: 2025-10

Locations

US (2)