Novel Unedited Allo Cell Therapy For High Risk T-Cell Malignancies Using CD7-Specific Car Expressed On T Cells (NEO-CRIMSON)
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.
⁃ • 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.
⁃ • 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.