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

• ClinicalTrials.gov Identifier: NCT04268706
• Recruitment Status: Active, not recruiting
• First Posted: February 13, 2020
• Last Update Posted: April 5, 2023
• Sponsor: Tessa Therapeutics
• Information provided by (Responsible Party): Tessa Therapeutics

Tracking Information

• First Submitted Date: February 11, 2020
• First Posted Date: February 13, 2020
• Last Update Posted Date: April 5, 2023
• Actual Study Start Date: February 1, 2021
• Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 3, 2021)

• 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

Original Primary Outcome Measures (submitted: February 12, 2020)

To assess the 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

Current Secondary Outcome Measures (submitted: February 3, 2021)

• 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 ]
  ORR
• Pilot: Duration of Response [ Time Frame: Minimum 24 months post-CD30.CAR-T infusion ]
  DOR
• Pilot: Progression Free Survival [ Time Frame: Minimum 24 months post-CD30.CAR-T infusion ]
  PFS
• Pilot: Overall Survival [ Time Frame: Minimum 24 months post-CD30.CAR-T infusion ]
  OS
• Pilot: Health Related quality of life (HRQoL) questionnaire [ Time Frame: Minimum 24 months post-CD30.CAR-T infusion ]
  QoL
• 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 ]
  Adverse events
• 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 ]
  ORR
• Pivotal: Progression Free Survival (PFS) [ Time Frame: Minimum 24 months post-CD30.CAR-T infusion ]
  PFS
• Pivotal: Duration of Response (DOR) [ Time Frame: Minimum 24 months post-CD30.CAR-T infusion ]
  DOR
• Pivotal: Overall Survival [ Time Frame: Minimum 24 months post-CD30.CAR-T infusion ]
  OS
• Pivotal: Health Related quality of life (HRQoL) questionnaire [ Time Frame: Minimum 24 months post-CD30.CAR-T infusion ]
  HRQoL

Original Secondary Outcome Measures (submitted: February 12, 2020)

• Number of patients with adverse events as a measure of safety and tolerability of CD30.CART cells [ Time Frame: Minimum 24 months post-CD30.CAR-T infusion ]
  Number of patients with treatment related adverse events as assessed by CTCAE v5.0
• Progression Free Survival (PFS) [ Time Frame: Minimum 24 months post-CD30.CAR-T infusion ]
  PFS
• Duration of Response (DOR) [ Time Frame: Minimum 24 months post-CD30.CAR-T infusion ]
  DOR
• Objective Response Rate as assessed by the Investigator [ Time Frame: Minimum 24 months post-CD30.CAR-T infusion ]
  ORR by Investigator
• Overall survival [ Time Frame: Minimum 24 months post-CD30.CAR-T infusion ]
  Survival
• Health Related quality of life (HRQoL) questionnaire [ Time Frame: Minimum 24 months post-CD30.CAR-T infusion ]
  QoL

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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 Classical Hodgkin Lymphoma
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: CD30.CAR-T
  Autologous CD30.CAR-T cells infused on Day 0 after the completion of lymphodepleting chemotherapy.
• Drug: Fludarabine
  Lymphodepletion chemotherapy (30 mg/m2/day) for 3 consecutive days
  Other Name: Fludara
• Drug: Bendamustine
  Lymphodepletion chemotherapy (70 mg/m2/day) for 3 consecutive days
  Other Name: Bendeka

Study Arms

Experimental: 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.

Interventions:

• Drug: CD30.CAR-T
• Drug: Fludarabine
• Drug: Bendamustine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: April 3, 2022): 97
• Original Estimated Enrollment (submitted: February 12, 2020): 90
• Estimated Study Completion Date: March 2037
• Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04268706
• Other Study ID Numbers: TESSCAR001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Tessa Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Tessa Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Helen Heslop, MD; Baylor College of Medicine

• PRS Account: Tessa Therapeutics
• Verification Date: April 2023