Clinical trial NCT05352828: Autologous CD30.CAR-T in Combination With Nivolumab in cHL Patients After Failure of Frontline Therapy
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Classical Hodgkin Lymphoma
Hodgkin Disease Refractory
Hodgkin Disease Recurrent
Keywords: cHL
Lead sponsor: Tessa Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2022-04-29
Enrollment: 15
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Safety of autologous CD30.CAR-T in combination with nivolumab
timeFrame: From first dose of nivolumab (Cycle 1) to end of nivolumab Cycle 4 (each cycle is 28 days)
Secondary outcomes:
measure: Anti-tumor activity using CR rate of autologous CD30.CAR-T in combination with nivolumab
timeFrame: Up to end of 10 weeks post-CD30.CAR-T treatment
measure: Overall response rate
timeFrame: Through study completion, an average of 3 years from Leukapheresis
measure: Duration of response
timeFrame: Through study completion, an average of 3 years from Leukapheresis
measure: Progression-free survival
timeFrame: Through study completion, an average of 3 years from Leukapheresis
Other outcomes:
measure: Overall survival
timeFrame: Through study completion, an average of 3 years from Leukapheresis
measure: Pharmacokinetics - Maximum concentration (Cmax)
timeFrame: Through study completion, an average of 3 years from Leukapheresis
measure: Pharmacokinetics - Time of maximum concentration (Tmax)
timeFrame: Through study completion, an average of 3 years from Leukapheresis
measure: Pharmacokinetics - Area under the curve
timeFrame: Through study completion, an average of 3 years from Leukapheresis
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Helen Heslop, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center
name: Sairah Ahmed, MD
role: PRINCIPAL_INVESTIGATOR
References: