CHIMERIC ANTIGEN RECEPTOR TREATMENT TARGETING CD70 (SEVENTY)

H-53163 CASEY

This study is for patients that have lymph gland disease called Hodgkin or non-Hodgkin Lymphoma or T/NK-lymphoproliferative disease and the patients condition has come back or has not gone away after treatment, including the best treatment we know for these diseases. Some patients with Lymphoma or T/NK-lymphoproliferative disease show signs of virus that is sometimes called Epstein Barr virus (EBV). This virus causes mononucleosis or glandular fever ("mono") before or at the time of their diagnosis. EBV is found in the cancer cells of up to half the patients with Hodgkin's and non-Hodgkin Lymphoma. This suggests that the EBV plays a role in causing Lymphoma. The cancer cells (in lymphoma) and some immune system cells infected by EBV are able to hide from the body's immune system and escape destruction. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. T cells have been used to treat patients with cancers. T cells, that have been trained to kill EBV infected cells can survive in blood and affect the tumor. We have treated over 80 people on studies using T cells to target these diseases. About half of those patients who had disease at the time they got the cells had responses including some patients with complete responses (meaning the cancer could no longer be detected). We think that if T cells are able to last longer in the body, they may have a better chance of killing EBV and EBV infected tumor cells. Therefore, in this study we will add a new gene to the EBV T cells that can cause the cells to live longer called C7R. We know that T cells need substances called cytokines (substances such as proteins released by specific cells of the immune system) to survive and that the cells may not get enough cytokines after the cells are infused into the body. We have added the gene C7R that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time. The purpose of this study is to find the largest safe dose of C7R-EBV T cells, and additionally to evaluate how long they can be detected in the blood and what affect they have on the cancer.

2024-04-01

2026-05-01

2042-04-01

Not yet recruiting

Early phase I

12

Procurement Inclusion Criteria: 1. Diagnosis of primary refractory or relapsed Acute Myeloid Leukemia (AML) with the exception of acute promyelocytic leukemia (APL). Patients with targetable mutations should have failed or be ineligible for targeted therapies (e.g. FLT3 inhibitors, IDH inhibitors or anti-CD33 drug conjugate) OR Patients with other relapsed or refractory CD70+ hematological malignancies that would be considered an indication for allogeneic Hematopoietic Stem Cell Transplant (HSCT) if remission can be achieved. (Patients with CD19+ malignancies only: must have failed or be ineligible to receive commercial CD19.CAR T cell treatments.) Primary refractory or resistant disease, defined as not achieving complete remission (CR) (i.e., a remaining blast count of 5% or more) after 1 to 2 cycles of intense induction therapy. Relapse is defined as (1) hematologic relapse after complete remission based on bone marrow blasts \>=5%, or reappearance of blasts in the blood, or development of extramedullary disease; (2) molecular relapse after minimal residual disease (MRD) negative, complete remission based on reoccurrence of MRD as assessed by RT-qPCR or by multi-parametric flow cytometry (MFC) 2. CD70 positive tumor with at least 30% CD70+ blasts by flow cytometry or immunohistochemistry (staining can be pending at time of procurement) 3. Age ≤75 years. NOTE: The first three (3) patients treated on the study will be adults (≥18 years of age) 4. Hemoglobin ≥ 7.0 g/dL (can be transfused) 5. If apheresis required to collect blood * PT and aPTT \<1.5x ULN * Serum Creatinine \< 2 x ULN * AST \< 5 x ULN 6. Informed consent Procurement Exclusion Criteria: 1. Diagnosis of acute promyelocytic leukemia (APL) 2. Active infection (bacterial, fungal, or viral) requiring ongoing treatment without improvement. 3. Known active infection with HIV or HTLV (collected blood will be sent for HIV/HTLV testing, separate testing prior to procurement not required) 4. Active second cancer (except non-melanoma skin cancer or in situ breast cancer or cervical cancer) or other cancer treated ≤ 2 years prior to enrollment 5. Ongoing treatment with immune suppression for prophylaxis/treatment of GVHD including high dose steroids (e.g. prednisone equivalent \> 0.5 mg/kg/day) Treatment Inclusion Criteria: 1. Diagnosis of primary refractory or relapsed Acute Myeloid Leukemia (AML) with the exception of acute promyelocytic leukemia (APL) Patients with targetable mutations should have failed or be ineligible for targeted therapies (e.g. FLT3 inhibitors, IDH inhibitors, or anti-CD33 drug conjugate). OR Patients with other relapsed or refractory CD70+ hematological malignancies that would be considered an indication for allogeneic Hematopoietic Stem Cell Transplant (HSCT) if remission can be achieved. Patients with CD19+ malignancies only: must have failed or be ineligible to receive commercial CD19.CAR T cell treatments. Primary refractory or resistant disease as defined by not achieving complete remission (CR) (i.e., a remaining blast count of 5% or more) after 1 to 2 cycles of intense induction therapy. Relapse is defined as (1) hematologic relapse after complete remission based on bone marrow blasts \>=5%, or reappearance of blasts in the blood, or development of extramedullary disease; (2) molecular relapse after minimal residual disease (MRD) negative, complete remission based on reoccurrence of MRD as assessed by RT-qPCR or by multi-parametric flow cytometry (MFC) 2. Confirmation from the patient's primary physician team of a suitable allogeneic hematopoietic stem cell transplant (HSCT) donor. OR Documentation that patient declines a potential subsequent HSCT) 3. CD70 positive tumor with at least 30% CD70+ blasts by flow cytometry or immunohistochemistry (tissue) 4. No systemic chemotherapy at least 2 weeks prior to treatment on study and must be recovered from all acute toxic effects of prior chemotherapy at time of treatment. 5. Age ≤ 75 years. NOTE: The first three (3) patients treated on the study should be adults (≥18 years of age). Thereafter, a thorough review of the safety data will be performed and submitted to the FDA for approval prior to enrolling pediatric patients. 6. Hemoglobin ≥ 7.0 g/dL (can be transfused) 7. Total bilirubin \< 3 times the upper limit of normal 8. AST/ALT \< 5 times the upper limit of normal 9. Estimated GFR ≥ 60ml/min 10. Pulse oximetry of \> 90% on room air 11. Karnofsky/Lansky score of ≥ 60% 12. 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. Male partner should use a condom 13. Informed consent obtained Treatment Exclusion Criteria: 1. Diagnosis of acute promyelocytic leukemia (APL) 2. Currently receiving any investigational agents or received any tumor vaccines within the previous 6 weeks. 3. Pregnant or lactating. 4. Active infection with HIV or HTLV 5. Clinically significant bacterial, fungal, or viral infection requiring ongoing therapy without improvement. 6. Cardiac criteria: Cardiac echocardiography with LVEF\<50%; Cardiac dysfunction NYHA III or IV; Clinically significant pericardial effusion. Confirmation of absence of these conditions within 6 months of treatment. 7. CNS abnormalities: Presence of CNS disease defined as detectable cerebrospinal blast cells in a sample of CSF with ≥ 5 WBCs per mm3 or known CNS tumors/chloromas 8. Use of serotherapy with Campath or Anti-Thymocyte Globulin (ATG) within the last 28 days 9. Use of Donor Lymphocyte Infusion (DLI) or other cellular therapy product within 28 days 10. Acute GVHD ≥ Grade 2 or moderate to severe (formerly extensive) chronic GVHD 11. High dose steroids \>1 mg/kg within preceding 5 days or currently receiving \>0.5mg/kg/day prednisone equivalent 12. Hyperleukocytosis (WBC ≥ 50K) or rapidly progressive disease that in the estimation of the investigator would compromise the ability of the patient to complete the study within 3 months of allogeneic HSCT

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 12, 'type': 'ESTIMATED'}}

2024-04-03