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

NCT ID: NCT05352828

Last Updated: 2023-04-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-25
• Study Completion Date: 2037-12-15

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.

Detailed Description

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.

Conditions

Classical Hodgkin Lymphoma; Hodgkin Disease Refractory; Hodgkin Disease Recurrent

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nivolumab and CD30.CAR-T

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

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Dose: 480 mg or 6 mg/kg Q4W

Autologous CD30.CAR-T

Intervention Type: DRUG

Dose: 2 x 10e8 cells/m2

Fludarabine

Intervention Type: DRUG

Dose: 30 mg/m2/day x 3 days

Bendamustine

Intervention Type: DRUG

Dose: 70 mg/m2/day x 3 days

Interventions

Nivolumab

Dose: 480 mg or 6 mg/kg Q4W

Intervention Type: DRUG

Autologous CD30.CAR-T

Dose: 2 x 10e8 cells/m2

Intervention Type: DRUG

Fludarabine

Dose: 30 mg/m2/day x 3 days

Intervention Type: DRUG

Bendamustine

Dose: 70 mg/m2/day x 3 days

Intervention Type: DRUG

Other Intervention Names

Opdivo; CD30-directed CAR-T cells; Fludara; Bendeka; Treanda

Eligibility Criteria

Inclusion Criteria

1. Signed ICF

2. Male or female patients who are 12 years of age and above

3. Relapsed or refractory CD30+ cHL following failure of a standard frontline chemotherapy

4. At least 1 lesion, which must be fluordeoxyglucose positron emission tomography (FDG-PET) avid and measurable by PET-CT scan

5. Adequate laboratory parameters including hematologic, renal, hepatic, and coagulation function

6. 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)

7. Anticipated life expectancy > 12 weeks

8. No active infections including COVID 19 at Screening

Exclusion Criteria

1. Evidence of lymphomatous involvement of the central nervous system (CNS)

2. 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

3. Symptomatic cardiovascular disease: Class III or IV according to the New York Heart Association (NYHA) Functional Classification

4. Active uncontrolled bleeding or a known bleeding diathesis

5. Inadequate pulmonary function defined as oxygen saturation by pulse oximetry < 90% on room air

6. Echocardiogram (ECHO) or Multi-gated Acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) < 45%

7. Prior receipt of salvage therapy, for relapsed or refractory cHL, including allogeneic or ASCT

8. Prior receipt of investigational CD30.CAR-T cells

9. Receiving any investigational agents or any tumor vaccines

10. Receiving any live/attenuated vaccines

11. Ongoing treatment with immunosuppressive drugs or chronic systemic corticosteroids

12. Unresolved > Grade 1 non-hematologic toxicity associated with any prior treatments

13. Previous history of known or suspected autoimmune disease within the past 5 years

14. Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity

15. Evidence of human immunodeficiency virus (HIV) infection

16. Evidence of active viral infection with hepatitis B virus (HBV)

17. Evidence of active viral infection with hepatitis C virus (HCV)

18. Active second malignancy or history of another malignancy within the last 3 years

19. History of hypersensitivity reactions to murine protein-containing products or other product excipients

20. Any allergic or adverse reaction to nivolumab, fludarabine, or bendamustine that precludes treatment with these agents

21. History of a significant irAE from prior immune checkpoint inhibitor therapy

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Tessa Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Helen Heslop, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Sairah Ahmed, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

City of Hope National Medical Center

Duarte, California, United States

University of Miami

Miami, Florida, United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Baylor College of Medicine

Houston, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

TESSCAR003

Identifier Type: -

Identifier Source: org_study_id