A Phase 2 Multi-Center Study Evaluating the Safety and Efficacy of CD30-Directed Genetically Modified Autologous T Cells (CD30.CAR-T) in Adult and Pediatric Patients With Relapsed or Refractory Classical Hodgkin Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- CD30.CAR-T
- Conditions
- Hodgkin Lymphoma, Adult
- Sponsor
- Tessa Therapeutics
- Enrollment
- 97
- Locations
- 5
- Primary Endpoint
- Pilot: Safety of autologous CD30.CAR-T
- Status
- Active, Not Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a two-part, Phase 2, multicenter, open-label, single arm study to evaluate the safety and efficacy of autologous CD30.CAR-T in adult and pediatric subjects with relapsed or refractory CD30+ classical Hodgkin Lymphoma.
Detailed Description
The Pilot part of the study will evaluate the safety, tolerability, and preliminary antitumor efficacy of CD30.CAR-T. The Pivotal part of the study will evaluate antitumor efficacy and further evaluate safety and tolerability. All study eligibility requirements, assessments, procedures, and follow-up are the same for patients in both Pilot and Pivotal parts of the study. Subjects who meet eligibility criteria will have their blood drawn by leukapheresis for manufacture the CD30.CAR-T cells. Subjects are allowed bridging chemotherapy, as per Investigator choice, while waiting for production of CD30.CAR-T. Lymphodepletion (LD) with fludarabine and bendamustine will be administered for 3 consecutive days starting on Day -5 to Day -3, prior to CD30.CAR-T infusion, which will be administered on Day 0 as a single IV infusion. Depending on disease status, eligible subjects may receive up to a total of two CD30.CAR-T infusions at the same dose, each with preceding LD chemotherapy. Subjects will be closely monitored for safety and efficacy throughout the Treatment Period until the end of study (EOS) visit at Month 24. Subjects will be followed for survival, withdrawal of consent or study closure, whichever occurs first. Health Related Quality of Life assessments will also be collected throughout the study. After the EOS visit, subjects will enter the long-term follow-up phase (LTFU) which will include survival follow-up, additional safety, efficacy and biomarker assessments, as clinically indicated.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Eligibility is determined prior to blood collection . Patients must satisfy the following criteria to be enrolled in the study:
- •Signed Informed Consent Form
- •Male or female patients who are 12 - 75 years of age
- •Histologically confirmed classical Hodgkin Lymphoma
- •Relapsed or refractory cHL that has failed at least 3 prior lines of therapy, including:
- •chemotherapy
- •BV and/or
- •PD-1 inhibitor Patients may have previously received an autologous and/or allogeneic stem cell transplant
- •CD30-positive tumor
- •At least 1 measurable lesion according to The Lugano Classification
Exclusion Criteria
- •Evidence of lymphomatous involvement of central nervous system (CNS)
- •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
- •Active uncontrolled bleeding or a known bleeding diathesis
- •Inadequate pulmonary function defined as pulse oximetry \< 90% on room air
- •ECHO or MUGA with LVEF \< 45%
- •On-going treatment with immunosuppressive drugs or chronic systemic corticosteroids
- •Having received:
- •Anti-CD30 antibody-based therapy within 4 weeks prior to CD30.CAR-T infusion
- •Prior investigational CD30.CAR-T
- •CD30 bispecific agent within 8 weeks prior to CD30.CAR-T infusion
Arms & Interventions
CD30 positive r/r classical Hodgkin Lymphoma
Patients with relapsed or refractory classical Hodgkin Lymphoma who have failed 3 prior lines of treatment, which may include a prior autologous and/or allogeneic stem cell transplant. Patients will be treated with autologous CD30.CAR-T cells.
Intervention: CD30.CAR-T
CD30 positive r/r classical Hodgkin Lymphoma
Patients with relapsed or refractory classical Hodgkin Lymphoma who have failed 3 prior lines of treatment, which may include a prior autologous and/or allogeneic stem cell transplant. Patients will be treated with autologous CD30.CAR-T cells.
Intervention: Fludarabine
CD30 positive r/r classical Hodgkin Lymphoma
Patients with relapsed or refractory classical Hodgkin Lymphoma who have failed 3 prior lines of treatment, which may include a prior autologous and/or allogeneic stem cell transplant. Patients will be treated with autologous CD30.CAR-T cells.
Intervention: Bendamustine
Outcomes
Primary Outcomes
Pilot: Safety of autologous CD30.CAR-T
Time Frame: Minimum 24 months post-CD30.CAR-T infusion
Adverse events
Pivotal: Anti-tumor effect of autologous CD30.CAR-T using objective response rate (ORR) as assessed by an Independent Radiology Review Committee (IRRC) per the Revised Criteria for Response Assessment: The Lugano Classification (Cheson, 2014)
Time Frame: As early as 6 weeks after CD30.CAR-T treatment
ORR
Secondary Outcomes
- Pilot: Overall Survival(Minimum 24 months post-CD30.CAR-T infusion)
- Pilot: Duration of Response(Minimum 24 months post-CD30.CAR-T infusion)
- Pilot: Progression Free Survival(Minimum 24 months post-CD30.CAR-T infusion)
- Pilot: Antitumor efficacy of autologous CD30.CAR-T using objective response rate (ORR) as assessed by an Independent Radiology Review Committee (IRRC) per the Revised Criteria for Response Assessment: The Lugano Classification (Cheson et al., 2014)(As early as 6 weeks after CD30.CAR-T treatment)
- Pilot: Health Related quality of life (HRQoL) questionnaire(Minimum 24 months post-CD30.CAR-T infusion)
- Pivotal: Number of patients with adverse events as a measure of safety and tolerability of CD30.CART cells(As early as 6 weeks after CD30.CAR-T treatment)
- Pivotal: Objective response rate (ORR as assessed by IRRC) per the Revised Criteria for Response Assessment: The Lugano Classification (Cheson, 2014)(Minimum 24 months post-CD30.CAR-T infusion)
- Pivotal: Progression Free Survival (PFS)(Minimum 24 months post-CD30.CAR-T infusion)
- Pivotal: Duration of Response (DOR)(Minimum 24 months post-CD30.CAR-T infusion)
- Pivotal: Overall Survival(Minimum 24 months post-CD30.CAR-T infusion)
- Pivotal: Health Related quality of life (HRQoL) questionnaire(Minimum 24 months post-CD30.CAR-T infusion)