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A Safety and Efficacy Study Evaluating CTX112 in Subjects With Relapsed or Refractory B-Cell Malignancies

Primary Purpose

B-cell Lymphoma, Non-Hodgkin Lymphoma, B-cell Malignancy

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CTX112
Sponsored by
CRISPR Therapeutics AG
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-cell Lymphoma focused on measuring CAR T, Non-Hodgkin Lymphoma (NHL), Lymphoma, Allogeneic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria: Age ≥18 years. Refractory or relapsed B cell malignancy. 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 CTX112 infusion. Key Exclusion Criteria: Prior allogeneic hematopoietic stem cell transplant (HSCT). Active or 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. Use of systemic anti-tumor therapy or investigational agent within 14 days or 5 half-lives, whichever is longer, of enrollment. Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy. Women who are pregnant or breastfeeding.

Sites / Locations

  • Research SiteRecruiting
  • Research SiteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CTX112

Arm Description

Administered by IV infusion following lymphodepleting chemotherapy.

Outcomes

Primary Outcome Measures

Phase 1 (Dose Escalation): Incidence of adverse events, defined as dose-limiting toxicities
Phase 2 (Cohort Expansion): Objective response rate

Secondary Outcome Measures

Duration of Response
Duration of Response (DOR) will only be reported for subjects who have had CR/PR events
Duration of Clinical Benefit (DOCB)
Progression Free Survival
Overall Survival

Full Information

First Posted
November 30, 2022
Last Updated
August 14, 2023
Sponsor
CRISPR Therapeutics AG
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1. Study Identification

Unique Protocol Identification Number
NCT05643742
Brief Title
A Safety and Efficacy Study Evaluating CTX112 in Subjects With Relapsed or Refractory B-Cell Malignancies
Official Title
A Phase 1/2, Open-Label, Multicenter, Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Anti-CD19 Allogeneic CRISPR-Cas9-Engineered T Cells (CTX112) in Subjects With Relapsed or Refractory B Cell Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 10, 2023 (Actual)
Primary Completion Date
January 2030 (Anticipated)
Study Completion Date
February 2030 (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 CTX112™ in subjects with relapsed or refractory B-cell malignancies.
Detailed Description
This is an open-label, multi-center Phase 1/2 study of CTX112 in subjects with relapsed/refractory B cell malignancies. CTX112 is an is allogeneic CD19-directed chimeric antigen receptor (CAR) T cell immunotherapy comprised of allogeneic T cells 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 Lymphoma, Non-Hodgkin Lymphoma, B-cell Malignancy, Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Large B-cell Lymphoma
Keywords
CAR T, Non-Hodgkin Lymphoma (NHL), Lymphoma, Allogeneic

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
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CTX112
Arm Type
Experimental
Arm Description
Administered by IV infusion following lymphodepleting chemotherapy.
Intervention Type
Biological
Intervention Name(s)
CTX112
Intervention Description
CTX112 (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 (Dose Escalation): Incidence of adverse events, defined as dose-limiting toxicities
Time Frame
From CTX112 infusion up to 28 days post-infusion
Title
Phase 2 (Cohort Expansion): Objective response rate
Time Frame
From CTX112 infusion up to 60 months post-infusion
Secondary Outcome Measure Information:
Title
Duration of Response
Description
Duration of Response (DOR) will only be reported for subjects who have had CR/PR events
Time Frame
From date of first objective response of complete response (CR)/partial response (PR) 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 of CR/PR until the relapse or death that followed the last response, assessed up to 60 months
Title
Progression Free Survival
Time Frame
From date of CTX112 infusion until date of disease progression or death due to any cause, assessed up to 60 months
Title
Overall Survival
Time Frame
From date of CTX112 infusion until date of death due to any cause, assessed up to 60 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Age ≥18 years. Refractory or relapsed B cell malignancy. 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 CTX112 infusion. Key Exclusion Criteria: Prior allogeneic hematopoietic stem cell transplant (HSCT). Active or 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. Use of systemic anti-tumor therapy or investigational agent within 14 days or 5 half-lives, whichever is longer, of enrollment. 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
Research Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Safety and Efficacy Study Evaluating CTX112 in Subjects With Relapsed or Refractory B-Cell Malignancies

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