Autologous CD30.CAR-T in Combination With Nivolumab in cHL Patients After Failure of Frontline Therapy

NCT05352828 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TESSCAR003
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 5

Brief Summary

This is a Phase 1b, multicenter, open-label, single arm study to evaluate the safety and efficacy of the combination therapy, CD30.CAR-T and the programmed cell death protein-1 (PD-1) checkpoint inhibitor, nivolumab, in patients aged 12 years of age and above with relapsed or refractory classical Hodgkin lymphoma (cHL) following failure of standard frontline therapy.

Conditions

Classical Hodgkin Lymphoma; Hodgkin Disease Refractory; Hodgkin Disease Recurrent

Keywords

cHL

Outcome Measures

Primary Outcomes (1)

• Safety of autologous CD30.CAR-T in combination with nivolumab

  DLT

  From first dose of nivolumab (Cycle 1) to end of nivolumab Cycle 4 (each cycle is 28 days)

Secondary Outcomes (4)

• Anti-tumor activity using CR rate of autologous CD30.CAR-T in combination with nivolumab

  Up to end of 10 weeks post-CD30.CAR-T treatment

• Overall response rate

  Through study completion, an average of 3 years from Leukapheresis

• Duration of response

  Through study completion, an average of 3 years from Leukapheresis

• Progression-free survival

  Through study completion, an average of 3 years from Leukapheresis

Other Outcomes (4)

• Overall survival

  Through study completion, an average of 3 years from Leukapheresis

• Pharmacokinetics - Maximum concentration (Cmax)

  Through study completion, an average of 3 years from Leukapheresis

• Pharmacokinetics - Time of maximum concentration (Tmax)

  Through study completion, an average of 3 years from Leukapheresis

Study Arms (1)

Nivolumab and CD30.CAR-T

EXPERIMENTAL

Study treatment will include 4 cycles of nivolumab and a single CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy of Fludarabine and Bendamustine).

Drug: Nivolumab; Drug: Autologous CD30.CAR-T; Drug: Fludarabine; Drug: Bendamustine

Interventions

Nivolumab DRUG

Dose: 480 mg or 6 mg/kg Q4W

Also known as: Opdivo

Nivolumab and CD30.CAR-T

Autologous CD30.CAR-T DRUG

Dose: 2 x 10e8 cells/m2

Also known as: CD30-directed CAR-T cells

Nivolumab and CD30.CAR-T

Fludarabine DRUG

Dose: 30 mg/m2/day x 3 days

Also known as: Fludara

Nivolumab and CD30.CAR-T

Bendamustine DRUG

Dose: 70 mg/m2/day x 3 days

Also known as: Bendeka, Treanda

Nivolumab and CD30.CAR-T

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed ICF
• Male or female patients who are 12 years of age and above
• Relapsed or refractory CD30+ cHL following failure of a standard frontline chemotherapy
• At least 1 lesion, which must be fluordeoxyglucose positron emission tomography (FDG-PET) avid and measurable by PET-CT scan
• Adequate laboratory parameters including hematologic, renal, hepatic, and coagulation function
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, or equivalent either Karnofsky performance status (for patients ≥ 16 years of age) or Lansky performance status (for patients \< 16 years of age)
• Anticipated life expectancy \> 12 weeks
• No active infections including COVID 19 at Screening

You may not qualify if:

• Evidence of lymphomatous involvement of the central nervous system (CNS)
• Presence of clinically relevant or active seizure disorder, stroke, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement
• Symptomatic cardiovascular disease: Class III or IV according to the New York Heart Association (NYHA) Functional Classification
• Active uncontrolled bleeding or a known bleeding diathesis
• Inadequate pulmonary function defined as oxygen saturation by pulse oximetry \< 90% on room air
• Echocardiogram (ECHO) or Multi-gated Acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) \< 45%
• Prior receipt of salvage therapy, for relapsed or refractory cHL, including allogeneic or ASCT
• Prior receipt of investigational CD30.CAR-T cells
• Receiving any investigational agents or any tumor vaccines
• Receiving any live/attenuated vaccines
• Ongoing treatment with immunosuppressive drugs or chronic systemic corticosteroids
• Unresolved \> Grade 1 non-hematologic toxicity associated with any prior treatments
• Previous history of known or suspected autoimmune disease within the past 5 years
• Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• Evidence of human immunodeficiency virus (HIV) infection

Sponsors & Collaborators

• Tessa Therapeutics: lead
• Bristol-Myers Squibb: collaborator

Study Sites (5)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Interventions

Nivolumab; fludarabine; fludarabine phosphate; Bendamustine Hydrochloride

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Helen Heslop, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Sairah Ahmed, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Upon successful leukapheresis to produce CD30.CAR-T cells, patients will enter the treatment phase of the study. Treatments will include 4 cycles of nivolumab and CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy). Patients will then enter the post-treatment follow-up phase of the study, whereby patients will undergo either autologous stem cell transplant or continue to receive up to 6 additional treatment cycles of nivolumab. Patients will be followed for response assessments and safety monitoring until end of study (EOS); approximately 3 years after leukapheresis. Long-term follow-up will continue with additional safety monitoring and survival for up to 15 years after Leukapheresis.

Study Record Dates

• First Submitted: April 8, 2022
• First Posted: April 29, 2022
• Study Start: July 25, 2022
• Primary Completion: December 15, 2025
• Study Completion (Estimated): December 15, 2037
• Last Updated: April 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)