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

• Status: Recruiting
• Trial end date: 2038-05-01
• 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. 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.

• 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; Texas Children's Hospital; The Methodist Hospital Research Institute; 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

1. 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.

2. CD7-positive tumor (≥20% CD7 positive blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory).

3. Agebe adults (>/=18 yrs of age).

4. Hgb ≥ 7.0 (can be transfused)

5. Life expectancy greater than 12 weeks

6. If pheresis required to collect blood:

• Cr < 1.5 upper limit normal

• AST < 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. 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

1. 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.

2. CD7-positive tumor (≥20% CD7+ blasts by flow cytometry or immunohistochemistry (tissue) assessed in a CLIA certified Flow Cytometry/Pathology laboratory.

3. Agebe adults (>/=18 yrs of age).

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

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

6. Estimated GFR > 60 mL/min.

7. Pulse oximetry of > 90% on room air

8. Karnofsky or Lansky score of ≥ 60.

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

10. Available autologous activated peripheral blood T cell products released by QA.

11. Life expectancy of greater than 8 weeks.

12. 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.

13. 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 (per investigator discretion).

5. Active infection with HIV.

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

7. Any of the following 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<30% or LVEF<50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA III or IV (Confirmation of absence of these conditions on echocardiogram within 12 months of treatment).

8. CNS abnormalities: Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF with ≥ 5 WBCs per mm3 (unless negative by the Steinherz/Bleyer algorithm); Presence of any CNS disorder such as an uncontrolled seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.