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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CD30 positive NHL subtypes | Experimental | (ALCL, PTCL-NOS, ENKTCL, DLBCL-NOS, PMBCL) Dose Level 1 Dose Level 2 Dose Level 3 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CD30.CAR-T | Drug | 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) |
| 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 |
| 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 |
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Inclusion Criteria:
Eligibility is determined priori to leukapheresis. Patients must satisfy the following criteria to be enrolled in this study:
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
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| Name | Affiliation | Role |
|---|---|---|
| Sairah Ahmed | MD Anderson | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope | Duarte | California | 91010 | United States | ||
| Sarah Cannon Research Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34515338 | Derived | Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2. |
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|
| 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 |
| Nashville |
| Tennessee |
| 37203 |
| United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| The University of Texas MD Anderson Cancer Centre | Houston | Texas | 77030 | United States |
| ID | Term |
|---|---|
| D017728 | Lymphoma, Large-Cell, Anaplastic |
| D016411 | Lymphoma, T-Cell, Peripheral |
| D054391 | Lymphoma, Extranodal NK-T-Cell |
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| ID | Term |
|---|---|
| D016399 | Lymphoma, T-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D016393 | Lymphoma, B-Cell |
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