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

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ClinicalTrials.gov Identifier: NCT04268706
Recruitment Status : Recruiting
First Posted : February 13, 2020
Last Update Posted : March 24, 2021
Sponsor:
Information provided by (Responsible Party):
Tessa Therapeutics

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
Hodgkin Lymphoma, Adult Hodgkin Disease Recurrent Hodgkin Disease Refractory Hodgkin Disease, Pediatric Drug: CD30.CAR-T Drug: Fludarabine Drug: Bendamustine 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 94 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 CD30 Positive Classical Hodgkin Lymphoma
Actual Study Start Date : February 1, 2021
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : February 2036


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 Name: Fludara

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




Primary Outcome Measures :
  1. Pilot: Safety of autologous CD30.CAR-T [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: As early as 6 weeks after CD30.CAR-T treatment ]
    ORR

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

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

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

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

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

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

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

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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04268706


Contacts
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Contact: Clinical Trials 65 63840755 clinicaltrials@tessacell.com

Locations
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United States, California
City of Hope Comprehensive Cancer Center Not yet recruiting
Duarte, California, United States, 91010
Contact: Matthew Mei, MD    833-310-2278    mamei@coh.org   
United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Peter Riedell, MD    773-702-8412    Priedell@medicine.bsd.uchicago.edu   
Contact: Katherine Eckert, MD    773-702-2023    keckert@medicine.bsd.uchicago.edu   
United States, Pennsylvania
Children's Hospital of Philadelphia Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Sue Rheingold, MD    215-590-5476    rheingold@chop.edu   
Contact: Laura Shinehouse, MD    267-425-7196    shinehousl@chop.edu   
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Ian Flinn, MD    615-329-7274    iflinn@tnonc.com   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sairah Ahmed, MD    713-794-4374    SAhmed3@mdanderson.org   
Sponsors and Collaborators
Tessa Therapeutics
Investigators
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Principal Investigator: Helen Heslop, MD Baylor College of Medicine
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Responsible Party: Tessa Therapeutics
ClinicalTrials.gov Identifier: NCT04268706    
Other Study ID Numbers: TESSCAR001
First Posted: February 13, 2020    Key Record Dates
Last Update Posted: March 24, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine
Bendamustine Hydrochloride
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents