CAR T-cells Against CD30 (HSP-CAR30) for Relapsed/ Refractory Hodgkin and T-cell Lymphoma.

Study Overview
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Brief Summary
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HSP-CAR30 is a cell suspension of genetically modified T-cells to express a second generation (4-1BBz) chimeric antigen receptor (CAR) directed against CD30. This is a phase I/IIa, interventional, single arm, open label, treatment study to evaluate the safety, tolerability and efficacy of HSP-CAR30 in patients with relapsed/refractory Hodgkin lymphoma and relapsed/refractory T-cell lymphoma expressing CD30.

Official Title
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Immunotherapy With Autologous CAR30 T Cells for Patients With Classic Hodgkin Lymphoma and Non-Hodgkin T-cell Lymphoma With CD30 Expression.

Conditions
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Hodgkin Lymphoma, Adult, T Cell Lymphoma

Intervention / Treatment
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* Biological: HSP-CAR30


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Classic Hodgkin lymphoma: Relapsed patients after autologous hematopoietic stem cell transplantation who have already received Brentuximab-Vedotin and anti-PDL1 antibodies, OR Primarily refractory patients who do not reach CR after rescue, including Brentuximab-Vedotin and anti-PDL1 antibodies. Anaplastic large T-cell lymphoma (ALK+/ALK-) and peripheral T-cell lymphoma (NOS/Angioimmunoblastic): >90% of tumor cells expressing CD30 determined by immunohistochemistry, AND Relapsed patients after autologous hematopoietic stem cell transplantation, OR Primarily refractory patients (after first line, including anthracycline) who do not achieve CR after rescue. All patients must sign an informed consent before starting any procedure. All patients must have measurable disease (detected by PET-CT) at the time of inclusion. Performance status: ECOG 0-1 FEV1> 39%; DLCO and FVC> 39% of NV. No significant ventricular dysfunction: EF >45%. Total bilirubin and transaminases <3 times the maximum normal value, unless attributable to lymphoma. Creatinine <2 times the normal maximum value and clearance> 40 mL/min. Exclusion Criteria: Performance status: ECOG 2-4 Prior allogeneic haematopoietic stem cell transplant. Active hepatitis B, C or HIV infection Active bacterial, fungal, or viral infection. Evidence of CNS involvement by lymphoma.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: Experimental: HSP-CAR30 (anti-CD30 CAR T cells) Dose escalation phase: Phase I: Ten patients will be treated with HSP-CAR30 (anti-CD30 CAR T-cells) with an escalation approach to define maximum tolerated dose (MTD) from 3 x 106/kg to 10 x 106/kg. Phase IIa: Twenty patients will be treated with HSP-CAR30 at MTD to evaluate efficacy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSP-CAR30 (anti-CD30 CAR T cells)<br>Phase I: Ten patients will be treated with HSP-CAR30 (anti-CD30 CAR T-cells) with an escalation approach to define maximum tolerated dose (MTD) from 3 x 106/kg to 10 x 106/kg. Phase IIa: Twenty patients will be treated with HSP-CAR30 at MTD to evaluate efficacy. | Biological: HSP-CAR30<br>* Anti-CD30 CAR T-cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess safety and toxicity of the administration of autologous anti-CD30 CAR T-cells | Number of patients with cytokine release syndrome and/or ICANs grade 1-4 according to ASBMT Consensus | 12 months | 
| To establish the maximum tolerated dose (MTD; defined as the dose that induces maximum limiting toxicity) of autologous anti-CD30 CAR T-cells in patients with refractory or relapsed classic Hodgkin or CD30 + T NHL. | Number of patients receiving maximum dose (1 x 10e7/kg CART+ cells) without DLT | 12 months | 
| To analyze the rate of complete responses at 3 months after the procedure |  | 24 months |