Genetically Engineered Donor Cells (Allogeneic C7R.CD30.CAR-EBVSTs) for the Treatment of Relapsed or Refractory CD30+ Lymphomas, CABAL2 Trial

Status: active

This phase I trial studies the safety, side effects, and best dose of genetically engineered donor (allogeneic) cells called C7R.CD30.chimeric antigen receptor (CAR)-Epstein Barr virus (EBV) specific T cells (EBVSTs) in treating CD30 positive (+) lymphomas that have come back after a period of improvement (relapsed) or that have not responded to previous treatment (refractory). The body has different ways of fighting infections and diseases. This trial combines two ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from diseases caused by bacteria, viruses and other foreign substances by binding to them to stop them from causing bad effects. T cells are special infection-fighting white blood cells that can kill other cells including cancer cells or cells that are infected with bacteria and viruses. Both antibodies and T cells have shown promise for treating patients with cancer, but neither has been strong enough to cure most patients. CD30 is found on the surface of some T cells and cancer cells, including lymphoma. Anti-CD30, an antibody used to treat lymphoma, has not cured many patients. In this study, the anti-CD30 antibody has been changed so that it is now joined to the T cells through a process called gene transfer. The resulting cells are called CD30.CAR T cells. A concern with administering CD30.CAR T cells is graft-versus-host disease (GVHD), a condition that occurs when donated cells (the graft) see the healthy tissues in the patient’s body (the host) as foreign and attack them. To lower the risk of GVHD, in this trial, EBVSTs are used that were trained in the lab to recognize EBV, the virus that causes mononucleosis or glandular fever. The process by which EBVSTs are made usually destroys T cells that can cause GVHD and lessens the risk of GVHD in patients. Furthermore, a molecule called C7R, which makes CAR T cells have deeper and longer anticancer effects in laboratory studies, has also been added to the study agent. Allogeneic C7R.CD30.CAR-EBVSTs may be a safe treatment for patients with relapsed or refractory CD30+ lymphomas.

Inclusion Criteria

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 * CD30+ aggressive B-cell lymphoma ** Refractory to second line therapy ** 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.
CD30-positive tumor as assayed in a Clinical Laboratory Improvement Amendments (CLIA) certified pathology laboratory.
Age 12 to 75 years.
Bilirubin ≤ 2 times the upper limit of normal (except for Gilbert syndrome, where the criteria will be bilirubin ≤ 3 times the upper limit of normal).
Aspartate aminotransferase (AST) ˂ 3 times the upper limit of normal.
Estimated glomerular filtration rate (eGFR) > 70 mL/min. (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] 2021 formula).
Pulse oximetry of > 90% on room air.
Karnofsky or Lansky score of > 60.
Recovered from all acute non-hematologic toxic effects of all prior chemotherapy.
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.
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

Received an investigational cell therapy or vaccine within the past 6 weeks.
Received an investigational small molecule within the past 2 weeks.
Received anti-CD30 antibody-based therapy within the previous 4 weeks.
History of hypersensitivity reactions to murine protein-containing products.
Pregnant or lactating.
Tumor in a location where enlargement could cause airway obstruction (determined at the investigators’ discretion).
Current use of systemic corticosteroids at a dose equivalent to higher than 10 mg/day of prednisone.
Active significant, uncontrolled bacterial, viral or fungal infection.
Symptomatic cardiac disease (New York Heart Association [NYHA] Class III or IV disease).

Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06176690.

United States

Texas

Houston

Center for Cell and Gene Therapy

Status: Active

Contact: Premal Lulla

Phone: 832-824-4847

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Status: Active

Contact: Premal Lulla

Phone: 832-824-4847

Texas Children's Hospital

Status: Active

Contact: Premal Lulla

Phone: 832-824-4847

PRIMARY OBJECTIVE:

I. To evaluate the safety of allogeneic iC9-C7R-expressing anti-CD30 CAR Epstein-Barr Virus-specific T lymphocytes (allogeneic Epstein-Barr virus-specific T lymphocytes modified to express a constitutively active IL7 receptor [C7R] and a chimeric antigen receptor [CAR] for CD30 [C7R.CD30.CAR-EBVSTs]) in patients with CD30+ refractory/relapsed in lymphomas.

SECONDARY OBJECTIVES:

I. To measure the antitumor effect of allogeneic C7R.CD30.CAR-EBVST cells including:

Ia. Objective response (OR) rate (ORR);

Ib. Duration of response (DR);

Ic. Stable disease (SD) rate;

Id. Duration of SD;

Ie. Progression free survival (PFS).

EXPLORATORY OBJECTIVES:

I. To measure expansion and persistence of allogeneic C7R.CD30.CAR-EBVST cells.

II. To evaluate association between immunological parameters, safety, and clinical response.

OUTLINE: This is a dose-escalation study of C7R.CD30.CAR-EBVSTs followed by a dose-expansion study.

Patients receive standard of care (SOC) lymphodepletion chemotherapy consisting of cyclophosphamide infusion over 60 minutes and fludarabine infusion over 30-60 minutes daily for 3 days (day -5 to day -2, but may start up to day -14 prior to day 0). Patients then receive C7R.CD30.CAR-EBVSTs intravenously (IV) over 1-10 minutes on day 0. Patients experiencing at least a partial response (PR) to the first C7R.CD30.CAR-EBVST infusion may receive up to 3 additional cycles of lymphodepletion + C7R.CD30.CAR-EBVSTs, repeating every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET) scans and blood sample collection throughout the study. Patients may also undergo an optional tumor biopsy on study.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months, every 6 months for 4 years, and then annually until 15 years from first C7R.CD30.CAR-EBVST infusion.

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Genetically Engineered Donor Cells (Allogeneic C7R.CD30.CAR-EBVSTs) for the Treatment of Relapsed or Refractory CD30+ Lymphomas, CABAL2 Trial

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