Cell Therapy for High Risk T-cell Malignancies Using CD7-Specific CAR Expressed on Non-Edited T Cells (CRIMSON-NE)
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.
∙ 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
⁃ 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 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.
∙ 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.