CAR-T cell therapy for dogs with CD20 positive B cell lymphoma

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Principal Investigator
Antonella Borgatti, DVM, MS, Dipl. ACVIM (Oncology), Dipl. ECVIM-CA
Professor, Oncology, Veterinary Clinical Sciences
Contact

Amber Winter, CVT
Research Professional 2
[email protected]
612-624-1352

Category:
Cancer/Oncology
Species:
Dog
Current status: On hold

Study title

Evaluation of xenogeneic CAR-T cell therapy for canine CD20+ B Cell lymphoma

Purpose of study

Canine B-cell lymphoma resembles human non-Hodgkin’s lymphoma, a cancer now successfully treated with Chimeric Antigen Receptor T cells (CAR-T cells). CAR-T cells are “T immune” cells that are genetically reprogrammed to seek out cancer, recognize it like a lock and key, and destroy it. This is an initial pilot trial to test the safety of a CAR-T cell therapy product in dogs with canine B-cell lymphoma towards the identification of more cost-effective and effective therapy for dogs with this disease. Prior to the CAR-T therapy, dogs will receive the immunosuppressive combination of two chemotherapy drugs with the dual goal of 1) killing at least a proportion of cancer cells, and 2) make room in the body for the CAR-T cells to expand.

Eligibility criteria

Eligible dogs will match these criteria:

  • all breeds allowed, except boxers
  • weigh 15-50 kg (33-110 lbs)
  • naive or relapsed lymphoma
  • Disease stages 1-4, substage A only
  • Cytologically confirmed lymphoma based on fine needle aspirates (FNA)
  • CD20+ determined from send-out FNA sample (collected at screening visit)
  • not currently receiving immunomodulatory drugs (Apoquel, mycophenolate, cyclosporine, or azathioprine)
  • prednisone use is ok if a 72 hour wash out period prior to CAR-T administration is safe
  • liver and kidney values within normal ranges as determined by blood and urine tests
  • normal neutrophil count, normal platelet count, normal hematocrit, no evidence of hypercalcemia, no evidence of lymphoblasts in circulation
  • disease does not involve the gastrointestinal tract, heart or lungs; patchy spleen/liver with disease infiltration may be acceptable provided substage a disease

Procedures

  1. Screening visit with physical exam, blood and urine collection, chest X-rays, abdominal ultrasound (possible sedation), lymph node measurements, fine needle aspirates (FNA) of lymph nodes. Within 1-3 days, we will determine if your dog has CD20-positive Diffuse Large B-cell Lymphoma (DLBCL). Dogs with positive tests can enroll, dogs with negative tests will not be able to enroll.
  2. First week
    • Day -3:  immunosuppression treatment with chemotherapy drugs, blood sampling, lymph node measurements and FNA. Dogs will go home with supportive medications to prevent side-effects of chemotherapy drugs. 
    • Day -2:  immunosuppression treatment with chemotherapy drugs
    • Day 0:  exam and blood sampling, then CAR-T cells by IV infusion. Dogs will be hospitalized in the VMC until Day 1 so we can monitor them closely and provide any care needed, including hospitalization in the ICU if indicated.
    • Day 1:  exam, blood sampling, lymph node measurements and FNA, dogs go home with supportive medications
  3. Recheck visits at Day 7, 14 for exams, blood sampling, lymph node measurements and FNA.
  4. Day 21:  study exit after recheck and lymph node progression assessment, exam, blood sampling, chest X-rays and abdominal ultrasound

Costs

The study is fully funded and will cover the costs of the visits outlined above, including the screening visit. Additional credits of up to $2000 ($1000 following Day 7 and Day 14 visits) will be made to the owners' VMC accounts only.