Anaplastic Large Cell Lymphoma, Diffuse Large B Cell Lymphoma, Extranodal NK/T-cell Lymphoma, Peripheral T Cell Lymphoma, Primary Mediastinal Large B-Cell Lymphoma (PMBCL)
Conditions
Keywords
CD30, r/r NHL, DLBCL, ALCL, ENKTCL, PMBCL, PTCL, adult
Brief summary
This is a phase 1 study to evaluate safety and dose-limiting toxicity of autologous CD30.CAR-T in subjects with relapsed or refractory CD30+ Non-Hodgkin Lymphoma
Detailed description
Adult patients with relapsed or refractory CD30-positive Non-Hodgkin Lymphoma who have failed standard available therapies and who meet eligibility criteria will have blood drawn to manufacture the CD30.CAR-T cells. CD30.CAR-T cells will be infused once following the completion of lymphodepleting chemotherapy with Bendamustine and Fludarabine. Subjects will be closely monitored for DLT and safety.
Interventions
DRUGCD30.CAR-T
Bendamustine and Fludarabine (3 days) Dose level 1: 2 x 108 cell/m2 CD30.CAR-T (Day 0) Dose level 2: 4 x 108 cell/m2 CD30.CAR-T (Day 0) Dose level 3: 6 x 108 cell/m2 CD30.CAR-T (Day 0)
Sponsors
Tessa Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Eligibility is determined priori to leukapheresis. Patients must satisfy the following criteria to be enrolled in this study: 1. Signed Informed Consent Form 2. Male or female patients who are 18-75 years of age 3. Histologically confirmed ALCL, PTCL- NOS, ENKTCL nasal type, DLBCL-NOS and PMBCL 4. Relapsed or refractory CD30-positive NHL who have failed all available standards of therapy. Patients may or may not have received an autologous or allogeneic HSCT CD30-positive tumor 5. At least 1 measurable lesion according to the Lugano Classification 6. ECOG PS of 0 to 1 or equivalent Karnofsky PS Anticipated life expectancy \>12 weeks
Exclusion criteria
1. CNS involvement by malignancy 2. Inadequate laboratory abnormalities at screening: Hgb ≤ 8.0 g/dL Total bilirubin \> 1.5 x ULN (\>2 x ULN for patients with Gilbert's syndrome) AST and ALT ≥ 5 x ULN CrCL ≤ 45 mL/min (as measured by Cockcroft-Gault equation) ANC ≤ 1000/uL Platelets ≤75,000/uL PR or INR \>1.5 x ULN aPTT\> 1.5 x ULN 3. Active uncontrolled bleeding or a known bleeding diathesis 4. Inadequate pulmonary function defined as pulse oximetry \< 90% on room air 5. Ongoing treatment with immunosuppressive drugs including calcineurin inhibitions, TNFalpha, mTOR, etc or chronic systemic corticosteroids (\>10 mg/day prednisone or equivalent for \>48 hours) 6. Received prior therapy of: Anti-CD30 Ab based therapy within the previous 8 weeks Previous CD30.CAR-T investigational product Bi-specific CD30 Ab within the previous 8 weeks Allogenic HSCT in the last 180 days Autologous HSCT within 90 days 7. Active GVHD requiring immune suppression regardless of grade 8. HIV positive 9. Active HBV and/or HCV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate safety and dose limiting toxicities (DLT) of autologous CD30.CAR-T and establish the recommended Phase dose | Day 0 to 28 for DLT | Incidence of DLTs and occurrence of study related adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate pharmacokinetics of autologous CD30.CAR-T | Start of infusion of CD30.CAR-T (Day 0) until year 5 | AUC (copies/ug DNA over time) |
| Objective Response Rate (ORR) | Start of CD30.CAR-T (Day 0) until progressive disease or start of new cancer therapy, whichever comes first, up to one year | ORR |
| Duration of Response (DOR) | Start of CD30.CAR-T (day 0) until progressive disease or death, whichever comes first, up to one year | DOR |
| Progression Free Survival (PFS) | Start of CD30.CAR-T (Day 0) until progressive disease or death, whichever comes first, up to one year | PFS |
Countries
United States
Outcome results
None listed