Phase 1 Study of Autologous CD30.CAR-T in Relapsed or Refractory CD30 Positive Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 1 Study of CD30-Directed Genetically Modified Autologous T-Cells (CD30.CAR-T) in Patients With Relapsed or Refractory CD30 Positive Non-Hodgkin Lymphoma

Conditions
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Anaplastic Large Cell Lymphoma, Peripheral T Cell Lymphoma, Extranodal NK/T-cell Lymphoma, Diffuse Large B Cell Lymphoma, Primary Mediastinal Large B-Cell Lymphoma (PMBCL)

Intervention / Treatment
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* Drug: CD30.CAR-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligibility is determined priori to leukapheresis. Patients must satisfy the following criteria to be enrolled in this study: Signed Informed Consent Form Male or female patients who are 18-75 years of age Histologically confirmed ALCL, PTCL- NOS, ENKTCL nasal type, DLBCL-NOS and PMBCL 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 At least 1 measurable lesion according to the Lugano Classification ECOG PS of 0 to 1 or equivalent Karnofsky PS Anticipated life expectancy >12 weeks Exclusion Criteria: CNS involvement by malignancy 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 Active uncontrolled bleeding or a known bleeding diathesis Inadequate pulmonary function defined as pulse oximetry < 90% on room air Ongoing treatment with immunosuppressive drugs including calcineurin inhibitions, TNFalpha, mTOR, etc or chronic systemic corticosteroids (>10 mg/day prednisone or equivalent for >48 hours) 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 Active GVHD requiring immune suppression regardless of grade HIV positive Active HBV and/or HCV

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD30 positive NHL subtypes<br>(ALCL, PTCL-NOS, ENKTCL, DLBCL-NOS, PMBCL) Dose Level 1 Dose Level 2 Dose Level 3 | Drug: CD30.CAR-T<br>* 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)<br>* Other names: CD30-directed genetically modified autologous T cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate safety and dose limiting toxicities (DLT) of autologous CD30.CAR-T and establish the recommended Phase dose | Incidence of DLTs and occurrence of study related adverse events | Day 0 to 28 for DLT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate pharmacokinetics of autologous CD30.CAR-T | AUC (copies/ug DNA over time) | Start of infusion of CD30.CAR-T (Day 0) until year 5 | 
| Objective Response Rate (ORR) | ORR | Start of CD30.CAR-T (Day 0) until progressive disease or start of new cancer therapy, whichever comes first, up to one year | 
| Duration of Response (DOR) | DOR | Start of CD30.CAR-T (day 0) until progressive disease or death, whichever comes first, up to one year | 
| Progression Free Survival (PFS) | PFS | Start of CD30.CAR-T (Day 0) until progressive disease or death, whichever comes first, up to one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD30, r/r NHL, DLBCL, ALCL, ENKTCL, PMBCL, PTCL, adult