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

Classical Hodgkin Lymphoma Clinical Trial

— ACTION  

Official title:

Phase 1b Study Evaluating the Safety and Efficacy of Autologous CD30.CAR-T in Combination With PD-1 Checkpoint Inhibitor (Nivolumab) in Relapsed or Refractory Classical Hodgkin Lymphoma Patients After Failure of Frontline Therapy (ACTION)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05352828
• Other study ID #: TESSCAR003
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: July 25, 2022
• Est. completion date: December 15, 2037

Study information

• Verified date: March 2023
• Source: Tessa Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: December 15, 2037
• Est. primary completion date: December 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Classical Hodgkin Lymphoma
• Hodgkin Disease
• Hodgkin Disease Recurrent
• Hodgkin Disease Refractory
• Lymphoma

Intervention

Drug:
• Nivolumab
Dose: 480 mg or 6 mg/kg Q4W
• Autologous CD30.CAR-T
Dose: 2 x 10e8 cells/m2
• Fludarabine
Dose: 30 mg/m2/day x 3 days
• Bendamustine
Dose: 70 mg/m2/day x 3 days

Locations

Country	Name	City	State
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	City of Hope National Medical Center	Duarte	California
United States	Baylor College of Medicine	Houston	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Miami	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Tessa Therapeutics	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall survival	OS	Through study completion, an average of 3 years from Leukapheresis
Other	Pharmacokinetics - Maximum concentration (Cmax)	Maximum concentration of CD30.CAR-T	Through study completion, an average of 3 years from Leukapheresis
Other	Pharmacokinetics - Time of maximum concentration (Tmax)	Time to peak concentration of CD30.CAR-T in the blood	Through study completion, an average of 3 years from Leukapheresis
Other	Pharmacokinetics - Area under the curve	Area under the curve of CD30.CAR-T in the blood	Through study completion, an average of 3 years from Leukapheresis
Primary	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	Anti-tumor activity using CR rate of autologous CD30.CAR-T in combination with nivolumab	CR rate	Up to end of 10 weeks post-CD30.CAR-T treatment
Secondary	Overall response rate	ORR	Through study completion, an average of 3 years from Leukapheresis
Secondary	Duration of response	DOR	Through study completion, an average of 3 years from Leukapheresis
Secondary	Progression-free survival	PFS	Through study completion, an average of 3 years from Leukapheresis