Novel Unedited Allo Cell Therapy For High Risk T-Cell Malignancies Using CD7-Specific Car T Cells

A regiszterben nem jelölt feltételek

• Procurement Inclusion Criteria:
• Diagnosis of recurrent T-cell acute lymphoblastic leukemia (T-ALL), T-cell acute lymphoblastic lymphoma (T-LL), 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
  • Relapsed post-allogeneic related donor (matched, mismatched, or haploidentical) HSCT from whom allogeneic CD7.CAR T cells can be manufactured.
  • 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 fit to proceed to the next step- whether high-resolution or confirmatory HLA testing OR donor work-up." Documentation of suitability 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.
• Hgb ≥ 7.0 g/dL (can be transfused)
• Life expectancy greater than 12 weeks
• Patients must have an available partially-HLA matched allogeneic EBV-specific T cell line on a BCM IRB approved protocol which can be used as treatment in the event of uncontrolled EBV reactivation.
• Informed consent explained to, understood by and signed by patient/LAR. Patient/LAR given copy of informed consent.
  • Procurement Exclusion Criteria:
• Active infection requiring antibiotics
• Active infection with HIV
• History of other cancer (except non-melanoma skin cancer or in situ breast cancer or cervical cancer) unless the tumor was successfully treated with curative intent at least 2 years before trial entry.
  • Prior HSCT Donor Procurement Criteria:
• Donor must be prior hematopoietic stem cell transplant donor for patient relapsed post-allogeneic HSCT who meets patient screening eligibility criteria and has signed screening informed consent.
  • Prior transplant donors will be screened with the standard blood bank donor questionnaire, medical history, and testing for infectious disease markers (IDMs; which may be pending at the time of blood collection). Medical history may be obtained by the patient's primary/referring transplant team if collection is being done remotely. The physician assessment, donor questionnaire, and IDMs will be reviewed by the principal investigator or appropriate designee to confirm/provide final eligibility determination and documented in the donor's medical record.
• Informed consent explained to, understood by and signed by donor/LAR. Donor/LAR given copy of informed consent.
  • Treatment Inclusion Criteria:
• Diagnosis of recurrent T-cell acute lymphoblastic leukemia (T-ALL), T-cell acute lymphoblastic lymphoma (T-LL), 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
  • Relapsed post-allogeneic related donor (matched, mismatched, or haploidentical) HSCT AND prior allogeneic donor available to donate blood for allogeneic CD7.CAR T-cell manufacture
  • 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 fit to proceed to the next step- whether high-resolution or confirmatory HLA testing OR donor work-up." Documentation of suitability 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 or tumor cells by flow cytometry or immunohistochemistry (tissue) assessed in a CLIA certified Flow Cytometry/Pathology laboratory.
• Age ≤75 years old.
• 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%.
• Recovered from acute toxic effects of prior treatments (i.e. chemotherapy) at least one week before entering this study.
• ≥ 60 days post-allogeneic HSCT at time of treatment.
• Patients must have an available partially-HLA matched allogeneic EBV-specific T cell line on a BCM IRB approved protocol which can be used as treatment in the event of uncontrolled EBV reactivation.
• 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.
• Informed consent explained to, understood by, and signed by patient/guardian. Patient/guardian given copy of informed consent.
  • Treatment Exclusion Criteria:
• Currently receiving any investigational agents or having received any tumor vaccines within the previous 4 weeks.
• History of hypersensitivity reactions to murine protein-containing products.
• Pregnant or lactating.
• Tumor in a location where enlargement could cause airway obstruction (per investigator discretion).
• Clinically significant infection or uncontrolled viral reactivation of EBV, CMV, Adv, BK-virus, or HHV-6.
• Evidence of acute GVHD \> Grade II or active chronic GVHD \> mild global severity score.
• Currently taking corticosteroids for therapy at a dose of \>0.5mg/kg prednisone equivalent.
• Patients who have received immunosuppressive treatment (IST) for GVHD within 28 days of infusion.
• Patients who have received donor lymphocyte infusion (DLI) within 28 days of infusion
• Any of the following cardiac criteria: Uncontrolled atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion; LVSF\<30% or LVEF\<50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA III or IV. \*Study requires cardiac echocardiography confirmation of absence of these conditions within 12 months of treatment.
• 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 within the past 12 months, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.