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

Hodgkin Lymphoma, Adult Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04268706
• Other study ID #: TESSCAR001
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 1, 2021
• Est. completion date: March 2037

Study information

• Verified date: April 2023
• Source: Tessa Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 97
• Est. completion date: March 2037
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
United States	University of Chicago Medical Center	Chicago	Illinois
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Tessa Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

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