CAR-T cell therapy for canine CD20+ B cell lymphoma

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Principal Investigator
Mike Henson, DVM, PhD, Diplomate ACVIM
Professor, Oncology, Veterinary Clinical Sciences
Co-investigator

Caitlin Feiock, DVM
Assistant Professor, Veterinary Clinical Sciences
[email protected]
612-624-2485

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

At least 250,000 dogs die of B-cell lymphoma in the USA every year. The current standard of care for canine B cell lymphoma is a multi-agent (CHOP) chemotherapy protocol. In dogs, CHOP chemotherapy requires weekly trips to the vet over approximately 5 months, costs $7k-12k, and puts 80-90% of dogs into remission for 9-12 months before relapse. 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. In this study, we will be conducting 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 efficacious therapy for dogs with this disease. Prior to the CAR-T therapy, dogs will receive either Elspar or Cyclophosphamide, with the dual goal of sensitizing the cancer cells to this immune therapy.

Eligibility criteria

Eligible dogs will match these criteria:

  • Body weight of 10-50kg (22-110lbs)

  • Clinical presentation

    • Peripheral multicentric lymphoma (minimum of 4 target peripheral lymph nodes evaluable)

    • Have naïve or relapsed disease, substage A only

  • Fine needle aspirate (in-house or reference lab) consistent with lymphoblastic/high grade lymphoma

  • VCOG Performance Score of 0 or 1

  • Concurrent medications of note:

    • Immunomodulatory drugs (Apoquel, mycophenolate, cyclosporine, azathioprine) are not allowed

      • Cytopoint is allowable and can be maintained for the study period

    • Prednisone used for the treatment of lymphoma is allowed, execpt:

      • if it's used for substage B disease

      • if patients are unable to tape off 48 hours prior to CAR-T dosing

      • if required for other pre-existing conditions during treatment

Procedures

  1. Screening day:  Physical exam (PE), blood and urine tests, fine needle aspirates (FNA), lymph node measurements, chest x-rays, abdominal ultrasound
    1. Enrollment:  IF the Sum of Longest Diameters (SoLD) from the lymph node measurements is <100mm, THEN we will proceed with scheduling the CAR-T injection and your dog will be randomized into receiving Elspar OR Cyclophosphamide pre-treatment
  2. Pre-treatment visit:
    1. Elspar (2-3 days prior to CAR-T):  Elspar 10,000 IU/m2 given, PE, blood tests, lymph node measurements, prescribed supportive meds as needed
    2. Cyclophosphamide (5 days prior to CAR-T):  Cyclophosphamide 500mg/m2 given intravenously (IV) with an overnight hospital stay for observation and concurrent medications given (consisting of IV Furosemide 3mg/kg and Mesna 200mg/m2)
  3. CAR-T administration (Day 0):  CAR-T injection into 4 lymph nodes, PE, blood tests, lymph node measurements
  4. Follow-up Visit (Day +7, Day +28):  PE, blood tests, lymph node measurements, FNA, chest x-rays and abdominal ultrasound on day +28
  5. Study Exit (3 months):  PE, blood and urine tests, lymph node measurements, FNA, chest x-rays, abdominal ultrasound
  • Unscheduled visits:  if your dog needs to be seen between the study visits above, they will consist of a PE, blood and urine tests, lymph node measurements, FNA
  • At any time the dog can be hospitalized in ICU for supportive fluids and other procedures as needed
  • Note, urinalysis may be added to recheck visits if clinical signs indicate it is needed

Costs

This study is fully funded and will cover the costs of visits as outlined above, including the screening visit, as well as $2,000 stipend upon completion of the study. If at any time, animal welfare in relation to disease or tumor progression necessitates study departure, a $2,000 care credit for your dog will be granted. Appropriate medications will be provided for your dog up to $2,000 if he/she develops any severe side effects due to the CAR-T treatment that require medical management, when care is provided at the University of Minnesota's Veterinary Medical Center.