Back to resultsA Safety and Efficacy Study Evaluating CTX110 in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON)
Primary Purpose
B-cell Malignancy, Non-Hodgkin Lymphoma, B-cell Lymphoma
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CTX110
Sponsored by
About this trial
This is an interventional treatment trial for B-cell Malignancy focused on measuring CAR T, Non-Hodgkin Lymphoma, NHL, Lymphoma, Allogeneic, Leukemia
Eligibility Criteria
Key Inclusion Criteria:
- For NHL patients: Age ≥18 years. For B cell ALL patients: age ≥18 years to ≤70 years
- 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.
- Eastern Cooperative Oncology Group performance status 0 or 1.
- Adequate renal, liver, cardiac and pulmonary organ function
- 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.
- Agree to participate in an additional long-term follow-up study after completion of this study.
Key Exclusion Criteria:
- Treatment with any gene therapy or genetically modified cell therapy, including CAR T cells.
- For NHL patients: prior allogeneic HSCT. For B cell ALL patients: prior allogeneic HSCT within 6 months, and/or any evidence of GvHD.
- History of central nervous system (CNS) involvement by malignancy
- History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
- Presence of bacterial, viral, or fungal infection that is uncontrolled or requires IV anti-infectives.
- Active HIV, hepatitis B virus or hepatitis C virus infection.
- 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.
- For NHL patients: Use of systemic anti-tumor therapy or investigational agent within 14 days or 5 half-lives, whichever is longer, of enrollment. For B cell ALL patients: Use of systemic antitumor therapy within 7 days of enrollment.
- Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy.
- Women who are pregnant or breastfeeding.
Sites / Locations
- Cedars SinaiRecruiting
- UCSF Medical Center
- Mayo ClinicRecruiting
- Emory University Winship Cancer InstituteRecruiting
- University of ChicagoRecruiting
- University of KansasRecruiting
- Markey Cancer Center, University of Kentucky
- University of MarylandRecruiting
- Beth Israel Deaconess Medical CenterRecruiting
- University of MinnesotaRecruiting
- Washington UniversityRecruiting
- Roswell Park Cancer InsituteRecruiting
- Weill Cornell Medical College / New York Presbyterian Hospital
- Duke UniversityRecruiting
- Oregon Health and Science UniversityRecruiting
- Fox Chase Cancer Center
- Sarah Cannon Research Institute
- Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical CenterRecruiting
- Texas Transplant InstituteRecruiting
- Virginia Commonwealth University Massey Cancer CenterRecruiting
- Swedish Cancer InstituteRecruiting
- Royal Prince Alfred HospitalRecruiting
- Peter MacCallum Cancer CentreRecruiting
- Sir Charles Gairdner HospitalRecruiting
- Princess Margaret Cancer CentreRecruiting
- CHU de LilleRecruiting
- Institut Paoli-CalmettesRecruiting
- Hôpital Saint AntoineRecruiting
- University of HamburgRecruiting
- University Hospital WürzburgRecruiting
- Clinica Universidad de Navarra
- Hospital Clínic de Barcelona
- Hospital Universitario de Salamanca
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CTX110
Arm Description
Administered by IV infusion following lymphodepleting chemotherapy.
Outcomes
Primary Outcome Measures
Phase 1 Part A (Dose Escalation), for all cohorts: Incidence of adverse events, defined as dose-limiting toxicities
Phase 1 Part B (Cohort Expansion) and Phase 2: Objective response rate
Secondary Outcome Measures
Duration of Response
Duration of Response (DOR) for subjects with objective response events
Duration of Clinical Benefit (DOCB)
Treatment-Failure-Free Survival (TFFS)
Progression Free Survival (PFS)
Overall Survival (OS)
Objective Response Rate (for B cell ALL)
For B cell ALL, objective response rate (ORR) (complete remission + complete remission with incomplete blood count recovery) will be assessed.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04035434
Brief Title
A Safety and Efficacy Study Evaluating CTX110 in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON)
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 22, 2019 (Actual)
Primary Completion Date
July 2026 (Anticipated)
Study Completion Date
August 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CRISPR Therapeutics AG
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Malignancy, Non-Hodgkin Lymphoma, B-cell Lymphoma, Adult B Cell ALL
Keywords
CAR T, Non-Hodgkin Lymphoma, NHL, Lymphoma, Allogeneic, Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
227 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CTX110
Arm Type
Experimental
Arm Description
Administered by IV infusion following lymphodepleting chemotherapy.
Intervention Type
Biological
Intervention Name(s)
CTX110
Intervention Description
CTX110 (CD19-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components
Primary Outcome Measure Information:
Title
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
Title
Phase 1 Part B (Cohort Expansion) and Phase 2: Objective response rate
Time Frame
From CTX110 infusion up to 60 months post-infusion
Secondary Outcome Measure Information:
Title
Duration of Response
Description
Duration of Response (DOR) for subjects with objective response events
Time Frame
From date of first objective response until date of disease progression or death due to any cause, assessed up to 60 months
Title
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
Title
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
Title
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
Title
Overall Survival (OS)
Time Frame
From date of first CTX110 infusion until date of death due to any cause, assessed up to 60 months
Title
Objective Response Rate (for B cell ALL)
Description
For B cell ALL, objective response rate (ORR) (complete remission + complete remission with incomplete blood count recovery) will be assessed.
Time Frame
From CTX110 infusion up to 60 months post-infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
For NHL patients: Age ≥18 years. For B cell ALL patients: age ≥18 years to ≤70 years
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.
Eastern Cooperative Oncology Group performance status 0 or 1.
Adequate renal, liver, cardiac and pulmonary organ function
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:
For NHL patients: prior allogeneic HSCT. For B cell ALL patients: prior allogeneic HSCT within 6 months, and/or any evidence of GvHD.
History of central nervous system (CNS) involvement by malignancy
History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
Presence of bacterial, viral, or fungal infection that is uncontrolled.
Positive for HIV, or active hepatitis B virus or hepatitis C virus infection.
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.
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.
Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy.
Women who are pregnant or breastfeeding.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Trials
Phone
+1 (877) 214-4634
Email
MedicalAffairs@crisprtx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Annie Weaver, PhD
Organizational Affiliation
CRISPR Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Cedars Sinai
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Individual Site Status
Recruiting
Facility Name
UCSF Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Completed
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Individual Site Status
Recruiting
Facility Name
Emory University Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Kansas
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph P McGuirk, DO
Phone
913-708-4032
Email
jmcguirk@kumc.edu
Facility Name
Markey Cancer Center, University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Individual Site Status
Completed
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jon Arnason, MD
Email
jarnason@bidmc.harvard.edu
First Name & Middle Initial & Last Name & Degree
Emma Logan, RN
Email
eklogan@bidmc.harvard.edu
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ashley Lyle, CRC-RN
Email
sonne054@umn.edu
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Individual Site Status
Recruiting
Facility Name
Roswell Park Cancer Insitute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
Individual Site Status
Recruiting
Facility Name
Weill Cornell Medical College / New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richard Maziarz, MD
Email
maziarzr@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Kevin Christmas, PhD
Phone
503-494-6474
Email
christmk@ohsu.edu
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Farrukh Awan, MD
Email
Farrukh.Awan@UTSouthwestern.edu
Facility Name
Texas Transplant Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paul Shaughnessy, MD
Email
Paul.Shaughnessy@MHShealth.com
First Name & Middle Initial & Last Name & Degree
Sherri Shade, RN, CCRC
Phone
210-575-4238
Email
Sherri.Shade@MHShealth.com
Facility Name
Virginia Commonwealth University Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Individual Site Status
Recruiting
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Individual Site Status
Recruiting
Facility Name
Royal Prince Alfred Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joy Ho, MBBS
Phone
+61 2 95158036
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Dickinson, MBBS, MD
Phone
+61 3 8559 7858
Email
michael.dickinson@petermac.org
Facility Name
Sir Charles Gairdner Hospital
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Individual Site Status
Recruiting
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Kuruvilla, MD
Phone
416-946-2821
Email
John.Kuruvilla@uhn.ca
First Name & Middle Initial & Last Name & Degree
Disha Prajapati
Phone
416-634-8737
Email
disha.prajapati@uhn.ca
Facility Name
CHU de Lille
City
Lille
ZIP/Postal Code
59000
Country
France
Individual Site Status
Recruiting
Facility Name
Institut Paoli-Calmettes
City
Marseille
ZIP/Postal Code
13009
Country
France
Individual Site Status
Recruiting
Facility Name
Hôpital Saint Antoine
City
Paris
ZIP/Postal Code
75012
Country
France
Individual Site Status
Recruiting
Facility Name
University of Hamburg
City
Hamburg
ZIP/Postal Code
20148
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Natascha von Huenerbein
Phone
+49 (0) 40 7410-23181
Email
n.von-huenerbein@uke.de
First Name & Middle Initial & Last Name & Degree
Marion Heinzelmann
Phone
+49 (0) 40 7410 - 54188
Email
mheinzel@uke.de
Facility Name
University Hospital Würzburg
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Individual Site Status
Recruiting
Facility Name
Clinica Universidad de Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Hospital Clínic de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Individual Site Status
Active, not recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Safety and Efficacy Study Evaluating CTX110 in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON)
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