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

This is an interventional treatment trial for T-cell Acute Lymphoblastic Lymphoma focused on measuring Autologous CAR T cells, T-cell acute lymphoblastic lymphoma, T-non-Hodgkin lymphoma Read More

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) or other cutaneous T-cell lymphomas

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. Age </=75 years old.. NOTE: The first three (3) patients treated on the study must be 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) or other cutaneous T-cell lymphomas

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. Age </=75 years old. NOTE: The first three (3) patients treated on the study must be 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 ≥ 50 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. Life expectancy of greater than 8 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 (per investigator discretion).
5. Clinically significant viral infection or uncontrolled viral reactivation of EBV, CMV, Adv, BK-virus, or HHV-6.
6. 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).
7. 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.