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

Launched by BAYLOR COLLEGE OF MEDICINE · Sep 27, 2018

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment for patients with certain types of blood cancers, specifically T-cell acute lymphoblastic leukemia (T-ALL), T-cell acute lymphoblastic lymphoma (T-LLy), and T-non-Hodgkin lymphoma (T-NHL). The treatment combines two powerful tools from the immune system: T cells, which are specialized blood cells that attack cancer cells, and an antibody called anti-CD7 that targets the cancer cells. Researchers will take T cells from patients, modify them in the lab to enhance their cancer-fighting abilities, and then reintroduce them into the patient’s body. The goal is to see how well these modified T cells can survive and eliminate the cancer.

To be eligible for this trial, participants must be diagnosed with one of the specified types of T-cell cancers, be suitable for a stem cell transplant, and have a compatible donor. They should also be between 18 and 75 years old and meet certain health criteria. Participants can expect to undergo a procedure to collect their blood, which will be processed to create the modified T cells. Throughout the trial, patients will be closely monitored for their health and response to the treatment. This study is still recruiting participants, and it’s important to note that the modified T cells being tested are not yet approved by the FDA, meaning this is an experimental treatment.

Gender

ALL

Eligibility 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 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
• • 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 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
• • 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. 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.
• • 11. 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.