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

Sponsor
Tessa Therapeutics (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04268706
Collaborator
(none)
97
Enrollment
5
Locations
1
Arm
192.9
Anticipated Duration (Months)
19.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
97 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Feb 1, 2021
Anticipated Primary Completion Date :
May 1, 2025
Anticipated Study Completion Date :
Mar 1, 2037

Arms and Interventions

Arm Intervention/Treatment
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.

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 Names:
  • Fludara

    • Drug: Bendamustine
    Lymphodepletion chemotherapy (70 mg/m2/day) for 3 consecutive days
    Other Names:
  • Bendeka

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Pilot: Safety of autologous CD30.CAR-T [Minimum 24 months post-CD30.CAR-T infusion]

      Adverse events

    2. 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) [As early as 6 weeks after CD30.CAR-T treatment]

      ORR

    Secondary Outcome Measures

    1. 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]

      ORR

    2. Pilot: Duration of Response [Minimum 24 months post-CD30.CAR-T infusion]

      DOR

    3. Pilot: Progression Free Survival [Minimum 24 months post-CD30.CAR-T infusion]

      PFS

    4. Pilot: Overall Survival [Minimum 24 months post-CD30.CAR-T infusion]

      OS

    5. Pilot: Health Related quality of life (HRQoL) questionnaire [Minimum 24 months post-CD30.CAR-T infusion]

      QoL

    6. 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]

      Adverse events

    7. 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]

      ORR

    8. Pivotal: Progression Free Survival (PFS) [Minimum 24 months post-CD30.CAR-T infusion]

      PFS

    9. Pivotal: Duration of Response (DOR) [Minimum 24 months post-CD30.CAR-T infusion]

      DOR

    10. Pivotal: Overall Survival [Minimum 24 months post-CD30.CAR-T infusion]

      OS

    11. Pivotal: Health Related quality of life (HRQoL) questionnaire [Minimum 24 months post-CD30.CAR-T infusion]

      HRQoL

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. CD30-positive tumor

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

    3. 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

    1. 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)]

    2. 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

    1. 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

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

    3. Evidence of human immunodeficiency virus (HIV) infection

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

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

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

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

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

    9. 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

    10. Any other serious, life-threatening, or unstable preexisting medical conditions

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    2 University of Chicago Medical Center Chicago Illinois United States 60637
    3 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    4 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    5 MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • Tessa Therapeutics

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Tessa Therapeutics
    ClinicalTrials.gov Identifier:
    NCT04268706
    Other Study ID Numbers:
    • TESSCAR001
    First Posted:
    Feb 13, 2020
    Last Update Posted:
    Apr 5, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Tessa Therapeutics
    r/r Hodgkin Lymphoma, CD30, adult, pediatrics
    Additional relevant MeSH terms:
    Lymphoma
    Hodgkin Disease
    Fludarabine
    Bendamustine Hydrochloride

    Study Results

    No Results Posted as of Apr 5, 2022