A Safety and Efficacy Study Evaluating CTX110 in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON)

March 20, 2024 updated by: CRISPR Therapeutics AG

A Phase 1/2 Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Allogeneic CRISPR-Cas9-Engineered T Cells (CTX110) in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON)

This is an open-label, multicenter, Phase 1/2 study evaluating the safety and efficacy of CTX110 in subjects with relapsed or refractory B-cell malignancies.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The study may enroll up to 227 subjects in total. CTX110 is a CD19-directed chimeric antigen receptor (CAR) T cell immunotherapy comprised of allogeneic T cells prepared for the treatment of B cell malignancies. The cells are from healthy adult volunteer donors that are genetically modified ex vivo using CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/ CRISPR-associated protein 9) gene editing components (single guide RNA and Cas9 nuclease).

Study Type

Interventional

Enrollment (Estimated)

227

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2050
        • Royal Prince Alfred Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Centre
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre
  • France
      • Lille, France, 59000
        • CHU de Lille
      • Marseille, France, 13009
        • Institut Paoli-Calmettes
      • Paris, France, 75012
        • Hôpital Saint Antoine
  • Germany
      • Hamburg, Germany, 20148
        • University of Hamburg
      • Würzburg, Germany, 97080
        • University Hospital Würzburg
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic de Barcelona
      • Salamanca, Spain, 37007
        • Hospital Universitario de Salamanca
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Clinica Universidad de Navarra
  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Cedars Sinai
      • San Francisco, California, United States, 94143
        • UCSF Medical Center
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Winship Cancer Institute
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Kansas
      • Westwood, Kansas, United States, 66205
        • University of Kansas
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Markey Cancer Center, University of Kentucky
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • Missouri
      • Saint Louis, Missouri, United States, 63130
        • Washington University
    • New York
      • Buffalo, New York, United States, 14203
        • Roswell Park Cancer Insitute
      • New York, New York, United States, 10021
        • Weill Cornell Medical College / New York Presbyterian Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Dallas, Texas, United States, 75390
        • Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center
      • San Antonio, Texas, United States, 78229
        • Texas Transplant Institute
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University Massey Cancer Center
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  1. For NHL patients: Age ≥18 years. For B cell ALL patients: age ≥18 years to ≤70 years
  2. Refractory or relapsed non-Hodgkin lymphoma, as evidenced by 2 or more lines of prior therapy, or histologically confirmed B cell ALL, refractory or relapsed.
  3. Eastern Cooperative Oncology Group performance status 0 or 1.
  4. Adequate renal, liver, cardiac and pulmonary organ function
  5. Female subjects of childbearing potential and male subjects must agree to use acceptable method(s) of contraception from enrollment through at least 12 months after CTX110 infusion.

Key Exclusion Criteria:

  1. For NHL patients: prior allogeneic HSCT. For B cell ALL patients: prior allogeneic HSCT within 6 months, and/or any evidence of GvHD.
  2. History of central nervous system (CNS) involvement by malignancy
  3. History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
  4. Presence of bacterial, viral, or fungal infection that is uncontrolled.
  5. Positive for HIV, or active hepatitis B virus or hepatitis C virus infection.
  6. Previous or concurrent malignancy, except basal cell or squamous cell skin carcinoma, adequately resected and in situ carcinoma of cervix, or a previous malignancy that was completely resected and has been in remission for ≥5 years.
  7. For NHL patients: Use of systemic anti-tumor therapy or investigational agent within 14 days or 5 half-lives, whichever is longer, of CTX110 infusion. For B cell ALL patients: Use of systemic antitumor therapy within 7 days of CTX110 infusion.
  8. Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy.
  9. Women who are pregnant or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CTX110
Administered by IV infusion following lymphodepleting chemotherapy.
Biological: CTX110
CTX110 (CD19-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phase 1 Part A (Dose Escalation), for all cohorts: Incidence of adverse events, defined as dose-limiting toxicities
Time Frame: From CTX110 infusion up to 28 days post-infusion
From CTX110 infusion up to 28 days post-infusion
Phase 1 Part B (Cohort Expansion) and Phase 2: Objective response rate
Time Frame: From CTX110 infusion up to 60 months post-infusion
From CTX110 infusion up to 60 months post-infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response
Time Frame: From date of first objective response until date of disease progression or death due to any cause, assessed up to 60 months
Duration of Response (DOR) for subjects with objective response events
From date of first objective response until date of disease progression or death due to any cause, assessed up to 60 months
Duration of Clinical Benefit (DOCB)
Time Frame: From date of first objective response until date of last disease progression or death, assessed up to 60 months
From date of first objective response until date of last disease progression or death, assessed up to 60 months
Treatment-Failure-Free Survival (TFFS)
Time Frame: From date of first CTX110 infusion until date of last disease progression or death due to any cause, assessed up to 60 months
From date of first CTX110 infusion until date of last disease progression or death due to any cause, assessed up to 60 months
Progression Free Survival (PFS)
Time Frame: From date of first CTX110 infusion until date of first disease progression or death due to any cause, assessed up to 60 months
From date of first CTX110 infusion until date of first disease progression or death due to any cause, assessed up to 60 months
Overall Survival (OS)
Time Frame: From date of first CTX110 infusion until date of death due to any cause, assessed up to 60 months
From date of first CTX110 infusion until date of death due to any cause, assessed up to 60 months
Objective Response Rate (for B cell ALL)
Time Frame: From CTX110 infusion up to 60 months post-infusion
For B cell ALL, objective response rate (ORR) (complete remission + complete remission with incomplete blood count recovery) will be assessed.
From CTX110 infusion up to 60 months post-infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

CRISPR Therapeutics AG

Investigators

  • Study Director: Annie Weaver, PhD, CRISPR Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 22, 2019

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

August 1, 2026

Study Registration Dates

First Submitted

July 22, 2019

First Submitted That Met QC Criteria

July 25, 2019

First Posted (Actual)

July 29, 2019

Study Record Updates

Last Update Posted (Actual)

March 21, 2024

Last Update Submitted That Met QC Criteria

March 20, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRSP-ONC-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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