CD30 CAR T Cells with or without Cyclophosphamide and Fludarabine in Treating Participants with Relapsed or Refractory CD30 Positive Lymphoma

Status: Active

Description

This phase I trial studies the side effects and best dose of CD30 CAR-expressing autologous T lymphocytes (CAR T cells) when given together with or without cyclophosphamide and fludarabine in treating participants with CD30 positive lymphoma that has come back or does not respond to treatment. CD30 CAR-expressing autologous T lymphocytes combine antibodies and T cells. Antibodies are proteins that protect the body from diseases caused by germs or toxic substances. They work by binding those germs or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cancer cells or cells that are infected with germs. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CD30 CAR-expressing autologous T lymphocytes, cyclophosphamide, and fludarabine together may work better in treating participants with CD30 positive lymphoma.

Eligibility Criteria

Inclusion Criteria

  • PROCUREMENT INCLUSION: Diagnosis of relapsed/refractory HL or NHL
  • PROCUREMENT INCLUSION: CD30 positive tumor as assayed in a Clinical Laboratory Improvement Act (CLIA) certified pathology laboratory (result can be pending at this time)
  • PROCUREMENT INCLUSION: Hemoglobin (Hgb) > 8.0 (may be a transfused value)
  • PROCUREMENT INCLUSION: Informed consent explained to, understood by and signed by patient/guardian; patient/guardian given copy of informed consent
  • PROCUREMENT INCLUSION: Karnofsky or Lansky score of > 60%
  • TREATMENT INCLUSION: Diagnosis and clinical course falling into one of the following categories: * Hodgkin lymphoma refractory to second line chemotherapy; relapsed or progressive after high dose therapy/autologous stem cell transplantation; relapsed or progressive after treatment with brentuximab or a checkpoint inhibitor * Aggressive non-Hodgkin lymphoma refractory to second line chemotherapy; relapsed or progressive after high dose therapy/autologous stem cell transplantation * ALK-negative anaplastic T cell lymphoma or other peripheral T-cell lymphoma refractory to first line chemotherapy; relapsed after first line therapy (possibly including high dose therapy/autologous stem cell transplantation) * ALK-positive anaplastic T cell lymphoma refractory to second line therapy; relapsed after second line therapy
  • TREATMENT INCLUSION: CD30-positive tumor as assayed in a CLIA certified pathology laboratory
  • TREATMENT INCLUSION: Age 16 to 75 for the first three patients on a dose level; thereafter, if no dose limiting toxicity (DLT), patients aged 12 to 75 can be treated on that dose level
  • TREATMENT INCLUSION: Bilirubin 1.5 times or less than the upper limit of normal
  • TREATMENT INCLUSION: Aspartate aminotransferase (AST) 3 times or less than the upper limit of normal
  • TREATMENT INCLUSION: Estimated glomerular filtration rate (GFR) > 70 mL/min
  • TREATMENT INCLUSION: Pulse oximetry of > 90% on room air
  • TREATMENT INCLUSION: Electrocardiography (EKG) shows no significant arrhythmias
  • TREATMENT INCLUSION: Karnofsky or Lansky score of > 60%
  • TREATMENT INCLUSION: Available autologous T cells with ≥ 15% expression of CD30CAR determined by flow-cytometry
  • TREATMENT INCLUSION: Recovered from all acute non-hematologic toxic effects of all prior chemotherapy
  • TREATMENT INCLUSION: Adequate pulmonary function with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 50% of expected corrected for hemoglobin
  • TREATMENT INCLUSION: 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
  • TREATMENT INCLUSION: Informed consent explained to, understood by and signed by patient or guardian; patient or guardian given a copy of the informed consent form

Exclusion Criteria

  • PROCUREMENT EXCLUSION: Active infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus (HTLV) (can be pending at this time)
  • PROCUREMENT EXCLUSION: Active bacterial fungal or viral infection
  • TREATMENT EXCLUSION: Currently receiving any investigational agents or received any tumor vaccines within the previous six weeks
  • TREATMENT EXCLUSION: Received anti-CD30 antibody-based therapy within the previous 4 weeks
  • TREATMENT EXCLUSION: Subjects with rapidly progressive disease, defined as kinetic failure to previous chemotherapy
  • TREATMENT EXCLUSION: Bulky disease (defined as a 10 cm mass or mediastinal disease with a transverse diameter exceeding 33% of the transthoracic diameter)
  • TREATMENT EXCLUSION: History of hypersensitivity reactions to murine protein-containing products
  • TREATMENT EXCLUSION: Pregnant or lactating
  • TREATMENT EXCLUSION: Tumor in a location where enlargement could cause airway obstruction
  • TREATMENT EXCLUSION: Current use of systemic corticosteroids at a dose equivalent to 0.5 mg/kg/day of prednisone or higher
  • TREATMENT EXCLUSION: Active hemorrhagic cystitis
  • TREATMENT EXCLUSION: Active bacterial, viral or fungal infection
  • TREATMENT EXCLUSION: Symptomatic cardiac disease (New York Heart Association [NYHA] class III or IV disease)

Locations & Contacts

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Active
Contact: Carlos Almeida Ramos
Phone: 832-824-4817
Center for Cell and Gene Therapy
Status: Active
Contact: Carlos Almeida Ramos
Phone: 832-824-4817
Texas Children's Hospital
Status: Active
Contact: Carlos Almeida Ramos
Phone: 832-824-4817

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the safety of one dose of autologous activated T lymphocytes (ATL), genetically modified to express an artificial chimeric antigen receptor (CAR) that targets the CD30 molecule (CD30 CAR-expressing autologous T lymphocytes [CD30.CAR]) and also contains the CD28 endodomain, in patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) after lymphodepleting chemotherapy.

SECONDARY OBJECTIVES:

I. To measure the survival of CD30.CAR transduced ATL in vivo.

II. To measure the anti-tumor effects of CD30.CAR transduced ATL in patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL).

OUTLINE: This is a dose-escalation study of CD30 CAR-expressing autologous T lymphocytes.

Participants who have not undergone an autologous transplant receive 3 daily doses of cyclophosphamide intravenously (IV) over 1 hour and fludarabine IV over 30 minutes finishing at least 48 hours before, but no later than 2 weeks prior to T cell infusion. All participants receive CD30 CAR-expressing autologous T lymphocytes IV over 1-10 minutes on day 0.

After completion of study treatment, participants are followed up at 3, 6, 9, and 12 months, then every 6 months for 4 years, and then annually for up to 15 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center

Principal Investigator
Carlos Almeida Ramos

Trial IDs

Primary ID RELY-30
Secondary IDs NCI-2018-00724, H-37966
Clinicaltrials.gov ID NCT02917083