Classical Hodgkin Lymphoma, Hodgkin Disease Recurrent, Hodgkin Disease Refractory
Conditions
Keywords
cHL
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.
Interventions
DRUGNivolumab
Dose: 480 mg or 6 mg/kg Q4W
DRUGAutologous CD30.CAR-T
Dose: 2 x 10e8 cells/m2
DRUGFludarabine
Dose: 30 mg/m2/day x 3 days
DRUGBendamustine
Dose: 70 mg/m2/day x 3 days
Sponsors
Bristol-Myers Squibb
Tessa Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of autologous CD30.CAR-T in combination with nivolumab | From first dose of nivolumab (Cycle 1) to end of nivolumab Cycle 4 (each cycle is 28 days) | DLT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | CR rate |
| Overall response rate | Through study completion, an average of 3 years from Leukapheresis | ORR |
| Duration of response | Through study completion, an average of 3 years from Leukapheresis | DOR |
| Progression-free survival | Through study completion, an average of 3 years from Leukapheresis | PFS |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics - Maximum concentration (Cmax) | Through study completion, an average of 3 years from Leukapheresis | Maximum concentration of CD30.CAR-T |
| Pharmacokinetics - Time of maximum concentration (Tmax) | Through study completion, an average of 3 years from Leukapheresis | Time to peak concentration of CD30.CAR-T in the blood |
| Pharmacokinetics - Area under the curve | Through study completion, an average of 3 years from Leukapheresis | Area under the curve of CD30.CAR-T in the blood |
| Overall survival | Through study completion, an average of 3 years from Leukapheresis | OS |
Countries
United States
Outcome results
None listed