Clinical Trials /

Phase 2 Study Evaluating Autologous CD30.CAR-T Cells in Patients With Relapsed/Refractory Hodgkin Lymphoma (CHARIOT)

NCT04268706

Description:

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.

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Study Evaluating Autologous CD30.CAR-T Cells in Patients With Relapsed/Refractory Hodgkin Lymphoma (CHARIOT)
  • Official Title: 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 CD30 Positive Classical Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: TESSCAR001
  • NCT ID: NCT04268706

Conditions

  • Hodgkin Lymphoma, Adult
  • Hodgkin Disease Recurrent
  • Hodgkin Disease Refractory
  • Hodgkin Disease, Pediatric

Interventions

DrugSynonymsArms
CD30.CAR-TCD30 positive r/r classical Hodgkin Lymphoma
FludarabineFludaraCD30 positive r/r classical Hodgkin Lymphoma
BendamustineBendekaCD30 positive r/r classical Hodgkin Lymphoma

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
CD30 positive r/r classical Hodgkin LymphomaExperimentalPatients 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.
  • CD30.CAR-T
  • Fludarabine
  • Bendamustine

Eligibility Criteria

        Inclusion Criteria:

        Eligibility is determined prior to blood collection . Patients must satisfy the following
        criteria to be enrolled in the study:

          1. Signed Informed Consent Form

          2. Male or female patients who are 12 - 75 years of age

          3. Histologically confirmed classical Hodgkin Lymphoma

          4. 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

          5. CD30-positive tumor

          6. At least 1 measurable lesion according to The Lugano Classification

          7. Laboratory parameters: Hematological, renal and hepatic functions, and coagulation
             parameters

               -  Hgb ≥ 8.0 g/dL

               -  Total bilirubin ≤ 1.5 × ULN

               -  AST and ALT ≤ 5 × the ULN

               -  CrCl > 45 mL/min

               -  ANC >1,000/µL

               -  Platelets >75,000/µL

               -  PT or INR ≤ 1.5 × ULN; PTT or aPTT ≤ 1.5 × ULN

          8. ECOG PS of 0 to 1 or equivalent [either Karnofsky PS (for patients ≥ 16 year of age)
             or Lansky PS (for patients < 16 years of age)]

          9. Anticipated life expectancy > 12 weeks

        Exclusion Criteria:

          1. Evidence of lymphomatous involvement of central nervous system (CNS)

          2. 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

          3. Active uncontrolled bleeding or a known bleeding diathesis

          4. Inadequate pulmonary function defined as pulse oximetry < 90% on room air

          5. ECHO or MUGA with LVEF < 45%

          6. On-going treatment with immunosuppressive drugs or chronic systemic corticosteroids

          7. 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

               -  Autologous HSCT within 90 days or allogeneic HSCT within 180 days prior to
                  CD30.CAR-T infusion

          8. Currently receiving any investigational agents within 4 weeks prior to study
             enrollment; or received any tumor vaccines within 6 weeks prior to CD30.CAR-T infusion

          9. Active acute or chronic graft versus host disease (GVHD) requiring immune suppression
             regardless of grade

         10. Evidence of human immunodeficiency virus (HIV) infection

         11. Seropositive for and with evidence of active viral infection with hepatitis B virus
             (HBV) or hepatitis C virus (HCV)

         12. Unresolved > Grade 1 non-hematologic toxicity associated with any prior treatments

         13. History of hypersensitivity reactions to murine protein-containing products or other
             product excipients

         14. Symptomatic cardiovascular disease: Class III or IV according to the New York Heart
             Association (NYHA) Functional Classification

         15. Active second malignancy or history of another malignancy within the last 3 years

         16. Women who are pregnant or intending to become pregnant; women who are breastfeeding;
             persons with procreative potential not using and not willing to use 2 highly effective
             methods of contraception

         17. Any other serious, life-threatening, or unstable preexisting medical conditions
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pilot: Safety of autologous CD30.CAR-T
Time Frame:Minimum 24 months post-CD30.CAR-T infusion
Safety Issue:
Description:Adverse events

Secondary Outcome Measures

Measure: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)
Time Frame:As early as 6 weeks after CD30.CAR-T treatment
Safety Issue:
Description:ORR
Measure:Pilot: Duration of Response
Time Frame:Minimum 24 months post-CD30.CAR-T infusion
Safety Issue:
Description:DOR
Measure:Pilot: Progression Free Survival
Time Frame:Minimum 24 months post-CD30.CAR-T infusion
Safety Issue:
Description:PFS
Measure:Pilot: Overall Survival
Time Frame:Minimum 24 months post-CD30.CAR-T infusion
Safety Issue:
Description:OS
Measure:Pilot: Health Related quality of life (HRQoL) questionnaire
Time Frame:Minimum 24 months post-CD30.CAR-T infusion
Safety Issue:
Description:QoL
Measure:Pivotal: Number of patients with adverse events as a measure of safety and tolerability of CD30.CART cells
Time Frame:As early as 6 weeks after CD30.CAR-T treatment
Safety Issue:
Description:Adverse events
Measure:Pivotal: Objective response rate (ORR as assessed by IRRC) per the Revised Criteria for Response Assessment: The Lugano Classification (Cheson, 2014)
Time Frame:Minimum 24 months post-CD30.CAR-T infusion
Safety Issue:
Description:ORR
Measure:Pivotal: Progression Free Survival (PFS)
Time Frame:Minimum 24 months post-CD30.CAR-T infusion
Safety Issue:
Description:PFS
Measure:Pivotal: Duration of Response (DOR)
Time Frame:Minimum 24 months post-CD30.CAR-T infusion
Safety Issue:
Description:DOR
Measure:Pivotal: Overall Survival
Time Frame:Minimum 24 months post-CD30.CAR-T infusion
Safety Issue:
Description:OS
Measure:Pivotal: Health Related quality of life (HRQoL) questionnaire
Time Frame:Minimum 24 months post-CD30.CAR-T infusion
Safety Issue:
Description:HRQoL

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tessa Therapeutics

Trial Keywords

  • r/r Hodgkin Lymphoma, CD30, adult, pediatrics

Last Updated

February 8, 2021