Chimeric Antigen Receptor Treatment Targeting CD70 (SEVENTY)

Launched by BAYLOR COLLEGE OF MEDICINE · Mar 28, 2024

Keywords

ClinConnect Summary

The SEVENTY clinical trial is testing a new treatment for patients with specific types of blood cancers, including certain forms of leukemia and lymphoma, where the disease has either come back or has not responded to previous treatments. This study focuses on using special immune cells called T cells that have been modified to better fight cancer cells infected with the Epstein-Barr virus (EBV). Researchers believe that by adding a gene called C7R to these T cells, they can help the cells live longer in the body, possibly improving their ability to attack the cancer.

To participate in this trial, patients generally need to be between 18 and 75 years old and have a certain type of blood cancer that expresses a specific marker called CD70. They should also have had limited success with other treatments and must be in good overall health. Participants can expect to receive a carefully monitored dose of the modified T cells and will be followed closely to see how well the treatment works and how long the cells last in their blood. This trial is still in the planning stages and has not yet begun enrolling patients, but it offers hope for those with difficult-to-treat cancers.

Gender

ALL

Eligibility criteria

• 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