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

• Status: Recruiting
• Trial end date: 2039-09-01
• Target enrollment: 0
• Participant gender: All

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 study combines two different ways of fighting disease, antibodies and T cells, hoping that they will work together. Antibodies are types of proteins that protect the body from bacterial and other diseases. T cells, also called 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 patients with cancers; they have shown promise, but have not been strong enough to cure most patients.

T lymphocytes 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. In some patients who have recently had a bone marrow or stem cell transplant, the number of T cells in their blood may not be enough to grow in the laboratory. In this situation, T cells may be collected from their previous transplant donor, who has a similar tissue type.

The antibody used in this study is called anti-CD5. It 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 laboratory, the investigators have also found that T cells work better if proteins that stimulate T cells are also added, 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 are going to 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 Food and Drug Administration.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Collaborators: Center for Cell and Gene Therapy, Baylor College of Medicine; Houston Methodist Hospital, TX; Texas Children's Hospital; The Methodist Hospital System
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate

Criteria

Procurement Inclusion Criteria

Referred patients will initially be consented for procurement of blood for generation of the transduced ATL. Eligibility criteria at this stage include:

1. 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: Suitable for allogeneic hematopoietic stem cell transplant (HSCT) with confirmation of an identified eligible allo-HSCT donor by FACT accredited institution

OR

Group B: Relapsed post-allogeneic HSCT with previous HSCT donor from whom allogeneic MAGENTA CAR T cells can be manufactured

AND with confirmation that the center plans to proceed with transplant if CD5.CAR treatment induces a complete remission.

2. 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.

3. Age less than or equal to 75 years old. NOTE: The first six (6) patients treated on the study will be adults (>18 yrs of age).

4. Hgb greater than or equal to 7.0 (can be transfused)

5. Life expectancy greater than 12 weeks

6. If pheresis required to collect blood:

• Creatinine <1.5 × upper limit normal

• AST <1.5 × upper limit normal

• PT and APTT <1.5 × upper limit normal

7. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.

Procurement Exclusion Criteria:

1. Active infection requiring antibiotics.

2. Active infection with HIV.

3. Clinically significant viral infection or uncontrolled viral reactivation of EBV, CMV, Adv, BK-virus, or HHV-6.

4. Cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF less than or equal to 30% or LVEF less than or equal to 50% or clinically significant pericardial effusion; Cardiac dysfunction NYHA III or IV (Confirmation of absence of these conditions within 12 months of treatment).

5. 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.

Treatment Inclusion Criteria:

1. 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: Suitable for allogeneic hematopoietic stem cell transplant (HSCT) with confirmation of an identified eligible allo-HSCT donor by FACT accredited institution

OR

Group B: Relapsed post-allogeneic HSCT with previous HSCT donor from whom allogeneic MAGENTA CAR T cells can be manufactured.

AND with confirmation that the center plans to proceed with transplant if CD5.CAR treatment induces a complete remission.

2. Age less than or equal to 75 years old. NOTE: The first six (6) patients treated on the study will be adults (>18 yrs of age).

3. Bilirubin less than 3 times the upper limit of normal.

4. AST less than 5 times the upper limit of normal.

5. Estimated GFR > 60 mL/min.

6. Pulse oximetry of > 90% on room air

7. Karnofsky or Lansky score of greater than or equal to 60%.

8. Recovered from acute toxic effects of prior chemotherapy at least one week before entering this study.

9. ≥ 60 days post-allogeneic HSCT at time of treatment.

10. Life expectancy of greater than 12 weeks.

11. Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.

12. Informed consent explained to, understood by, and signed by patient/guardian. Patient/guardian given copy of informed consent.

Treatment Exclusion Criteria:

1. Currently receiving any investigational agents or having received any tumor vaccines within the previous 6 weeks.

2. History of hypersensitivity reactions to murine protein-containing products.

3. Pregnant or lactating.

4. Tumor in a location where enlargement could cause airway obstruction.

5. Active infection with HIV.

6. Clinically significant viral infection or uncontrolled viral reactivation of EBV, CMV, Adv, BK-virus, or HHV-6.

7. Evidence of acute GVHD > Grade II or active chronic GVHD > mild global severity score

8. Currently taking corticosteroids for therapy of GVHD at a dose of >0.5mg/kg prednisone equivalent

9. Patients who have received Immunosuppressive Treatment (IST) for GVHD within 28 days of infusion

10. Patients who have received donor lymphocyte infusion (DLI) within 28 days of infusion

11. Cardiac criteria: Prolonged QT syndrome; Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Cardiac echocardiography with LVSF less than or equal to 30% or LVEF less than or equal to 50%; Cardiac dysfunction NYHA III or IV; Cardiac echocardiography with clinically significant pericardial effusion.

12. CNS abnormalities: Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF with greater than or equal to 5 WBCs per mm3; History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.