Clinical trial NCT04268706: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hodgkin Lymphoma, Adult
Hodgkin Disease Recurrent
Hodgkin Disease Refractory
Hodgkin Disease, Pediatric
Keywords: r/r Hodgkin Lymphoma, CD30, adult, pediatrics
Lead sponsor: Tessa Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-02-13
Enrollment: 97
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Pilot: Safety of autologous CD30.CAR-T
timeFrame: Minimum 24 months post-CD30.CAR-T infusion
measure: 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)
timeFrame: As early as 6 weeks after CD30.CAR-T treatment
Secondary outcomes:
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)
timeFrame: As early as 6 weeks after CD30.CAR-T treatment
measure: Pilot: Duration of Response
timeFrame: Minimum 24 months post-CD30.CAR-T infusion
measure: Pilot: Progression Free Survival
timeFrame: Minimum 24 months post-CD30.CAR-T infusion
measure: Pilot: Overall Survival
timeFrame: Minimum 24 months post-CD30.CAR-T infusion
measure: Pilot: Health Related quality of life (HRQoL) questionnaire
timeFrame: Minimum 24 months post-CD30.CAR-T infusion
measure: Pivotal: Number of patients with adverse events as a measure of safety and tolerability of CD30.CART cells
timeFrame: As early as 6 weeks after CD30.CAR-T treatment
measure: Pivotal: Objective response rate (ORR as assessed by IRRC) per the Revised Criteria for Response Assessment: The Lugano Classification (Cheson, 2014)
timeFrame: Minimum 24 months post-CD30.CAR-T infusion
measure: Pivotal: Progression Free Survival (PFS)
timeFrame: Minimum 24 months post-CD30.CAR-T infusion
measure: Pivotal: Duration of Response (DOR)
timeFrame: Minimum 24 months post-CD30.CAR-T infusion
measure: Pivotal: Overall Survival
timeFrame: Minimum 24 months post-CD30.CAR-T infusion
measure: Pivotal: Health Related quality of life (HRQoL) questionnaire
timeFrame: Minimum 24 months post-CD30.CAR-T infusion
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Helen Heslop, MD
role: PRINCIPAL_INVESTIGATOR
References: