A Safety and Efficacy Study Evaluating CTX120 in Subjects With Relapsed or Refractory Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT04244656
• Recruitment Status: Active, not recruiting
• First Posted: January 28, 2020
• Last Update Posted: July 18, 2022
• Sponsor: CRISPR Therapeutics AG
• Information provided by (Responsible Party): CRISPR Therapeutics ( CRISPR Therapeutics AG )

Study Description

Brief Summary:

This is a single-arm, open-label, multicenter, Phase 1 study evaluating the safety and efficacy of CTX120 in subjects with relapsed or refractory multiple myeloma.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Biological: CTX120	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Anti-BCMA Allogeneic CRISPR-Cas9-Engineered T Cells (CTX120) in Subjects With Relapsed or Refractory Multiple Myeloma
• Actual Study Start Date: January 22, 2020
• Estimated Primary Completion Date: November 2026
• Estimated Study Completion Date: January 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: CTX120; Administered by IV infusion following lymphodepleting chemotherapy.	Biological: CTX120; CTX120 B-cell maturation antigen (BCMA)-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components.

Outcome Measures

Primary Outcome Measures :

1. Part A (dose escalation): Incidence of adverse events [ Time Frame: From CTX120 infusion up to 28 days post-infusion ]
   Adverse events defined as dose-limiting toxicities
2. Part B (cohort expansion): Objective response rate [ Time Frame: From CTX120 infusion up to 60 months post-infusion ]
   Objective response rate per International Myeloma Working Group (IMWG) response criteria.

Secondary Outcome Measures :

1. Progression Free Survival [ Time Frame: From date of CTX120 infusion and date of disease progression or death due to any cause, assessed up to 60 months ]
2. Overall Survival [ Time Frame: From date of CTX120 infusion until date of death due to any cause, assessed up to 60 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

1. Age ≥18 years.
2. Relapsed or refractory multiple myeloma, as defined by IMWG response criteria and treatment with at least 2 prior lines of therapy.
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 CTX120 infusion.

Key Exclusion Criteria:

1. Prior allogeneic stem cell transplant (SCT).
2. Less than 60 days from autologous SCT at time of screening and with unresolved serious complications.
3. Prior treatment with any gene therapy or genetically modified cell therapy, including CAR T cells or natural killer cells, or BCMA-directed therapy.
4. Evidence of direct central nervous system (CNS) involvement by multiple myeloma.
5. History or presence of clinically relevant CNS pathology such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with CNS involvement.
6. Unstable angina, clinically significant arrhythmia, or myocardial infarction within 6 months of enrollment.
7. Active HIV, hepatitis B virus or hepatitis C virus infection.
8. 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.
9. Use of systemic anti-tumor therapy or investigational agent within 14 days prior to enrollment.
10. Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy.
11. Women who are pregnant or breastfeeding.

Contacts and Locations

Locations

United States, Illinois

University of Chicago

Chicago, Illinois, United States, 60637

United States, Oregon

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Tennessee

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

Australia, New South Wales

Royal Prince Alfred Hospital

Sydney, New South Wales, Australia, 2050

Australia, Victoria

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia, 3000

Canada, Ontario

University Health Network, Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G 1X6

Spain

Institut Catala d'Oncologia Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain, 08916

Universidad de Navarra

Pamplona, Navarra, Spain, 31008

Hospital Universitario de Salamanca

Salamanca, Spain, 37007

Sponsors and Collaborators

CRISPR Therapeutics AG

Investigators

• Study Chair: Sarah Cohen, MD; CRISPR Therapeutics

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bruno B, Wasch R, Engelhardt M, Gay F, Giaccone L, D'Agostino M, Rodriguez-Lobato LG, Danhof S, Gagelmann N, Kroger N, Popat R, Van de Donk NWCJ, Terpos E, Dimopoulos MA, Sonneveld P, Einsele H, Boccadoro M. European Myeloma Network perspective on CAR T-Cell therapies for multiple myeloma. Haematologica. 2021 Aug 1;106(8):2054-2065. doi: 10.3324/haematol.2020.276402.

• Responsible Party: CRISPR Therapeutics AG
• ClinicalTrials.gov Identifier: NCT04244656
• Other Study ID Numbers: CRSP-ONC-002
• First Posted: January 28, 2020
• Last Update Posted: July 18, 2022
• Last Verified: July 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by CRISPR Therapeutics ( CRISPR Therapeutics AG ):

CAR T; Allogeneic; Multiple myeloma; CRISPR-Cas9

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases