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A Study of CLN-978 in Patients With Relapsed or Refractory (R/R) B Cell Non-Hodgkin Lymphoma (B-NHL)

Sponsor
Cullinan Oncology, LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05879744
Collaborator
(none)
90
Enrollment
5
Locations
2
Arms
46
Anticipated Duration (Months)
18
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

CLN-978-001 is a Phase 1, open-label, dose escalation and dose expansion study of CLN-978 in patients with Relapse/Refractory (R/R) B-cell Non-Hodgkin Lymphoma (B-NHL).

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
90 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Open-label, Dose Escalation and Dose Expansion Study of CLN-978 in Patients With Relapsed/Refractory (R/R) B-cell Non-Hodgkin Lymphoma (B-NHL)
Actual Study Start Date :
May 31, 2023
Anticipated Primary Completion Date :
Nov 1, 2026
Anticipated Study Completion Date :
Apr 1, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part A Dose Escalation

Patients with R/R B-NHL treated with CLN-978 in dose escalation cohorts

Drug: CLN-978
CD19xCD3 T cell engager
Experimental: Part B Dose Expansion

Patients with R/R DLBCL, R/R FL and other R/R B-NHL treated with CLN-978 at a dose selected from the Part A Dose Escalation arm.

Drug: CLN-978
CD19xCD3 T cell engager

Outcome Measures

Primary Outcome Measures

  1. Safety and tolerability of CLN-978 based on AEs, AESIs, and SAEs [24 months]

    Incidence and severity of adverse events (AEs)/adverse events of special interest (AESIs)/serious adverse events (SAEs); incidence of dose interruptions and delays

  2. Define dose regimen for CLN-978 [24 months]

    Dose-limiting Toxicities (DLTs)

Secondary Outcome Measures

  1. Assess preliminary efficacy of CLN-978 by overall response in patients with selective histologies of R/R B-NHL [24 months]

    Overall response rate (ORR)

  2. Assess preliminary efficacy of CLN-978 by complete response in patients with selective histologies of R/R B-NHL [24 months]

    Complete response (CR)

  3. Assess preliminary efficacy of CLN-978 by duration of response in patients with selective histologies of R/R B-NHL [24 months]

    Duration of response (DOR)

  4. Select PK parameters of CLN-978: AUC [24 months]

    Area under-the-concentration-time curve of CLN-978

  5. Select PK parameters of CLN-978: Cmax [24 months]

    Maximum concentration of CLN-978

  6. Select PK parameters of CLN-978: Half-life [24 months]

    Half-life of CLN-978

  7. Immunogenicity of CLN-978 and potential impact on drug exposure [24 months]

    Incidence of anti-drug antibodies to CLN-978

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) PS ≤ 2

  • Documented diagnosis of one of the below CD19+ B-cell neoplasms according to WHO classification (Swerdlow et al., 2016) or WHO classification 2008:

  1. Diffuse large B-cell lymphoma - de novo or transformed

  2. High-grade B-cell lymphoma

  3. Primary mediastinal large B-cell lymphoma

  4. Follicular lymphoma

  5. Mantle cell lymphoma

  6. Marginal zone lymphoma (nodal, extranodal, or mucosa-associated)

  • Relapsed, progressive, and/or refractory disease after at least 2 lines of therapy.

  • For Part B expansion cohorts:

  1. Cohort B1: R/R DLBCL that has relapsed after at least 2 prior therapies including a CD20 monoclonal antibody and anthracycline.

  2. Cohort B2: R/R FL (grade 1-3a) that has relapsed after at least 2 prior therapies including CD20 monoclonal antibody and an alkylating agent.

  3. Cohort B3: Other R/R B-NHL.

  • Measurable disease defined as ≥1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on computed tomography (CT) scan or magnetic resonance imaging (MRI) AND baseline fluorodeoxyglucose-positron emission tomography (FDG-PET) scan demonstrating positive lesion(s) compatible with CT- or MRI-defined anatomical tumor sites.

  • Laboratory parameters including the following:

  1. Lymphocyte count < 5 x 10^9/L

  2. Platelet count ≥ 75 x 10^9/L

  3. Absolute neutrophil count ≥ 1.0 x 10^9/L; growth factor support allowed in cases of documented bone marrow involvement

  4. Hemoglobin ≥ 9 g/dL, with or without transfusion

  5. Creatinine clearance ≥ 45 mL/min

  6. Total bilirubin ≤ 1.5 × upper limit of normal (ULN), except patients with confirmed Gilbert's Syndrome

  7. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN (unless attributed to hepatic involvement by lymphoma)

Exclusion Criteria:

  • Primary CNS lymphoma or known CNS involvement by lymphoma at study screening

  • Known past or current malignancy other than the inclusion diagnosis

  • Known clinically significant cardiac disease

  • Significant central nervous system disease

  • Prior organ allograft

  • Confirmed history or current autoimmune disorder or other disease requiring ongoing immune suppression

  • Active Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), or known Human Immunodeficiency Virus (HIV) infection

  • Live virus vaccines within 28 days of the first dose of CLN-978, during treatment, and until the end of last dose of CLN-978

  • Known active, clinically significant bacterial, viral, fungal, mycobacterial, parasitic, or other infection, including coronavirus disease of 2019 (COVID-19) infection, at the time of enrollment or within 7 days of the first dose of CLN-978.

  • Prior treatment with any of the following:

  1. Allogeneic HSCT

  2. Autologous HSCT within 30 days prior to the first dose of CLN-978

  3. Chimeric antigen receptor T cell therapy (CAR-T) within 30 days prior to the first dose of CLN-978

  4. Any investigational CD19 x CD3 T cell engager (TCE)

  5. Unconjugated CD19 monoclonal antibody ≤ 4 weeks prior to the first dose CLN-978

  6. Radio-conjugated or CD19 antibody-drug conjugate ≤ 12 weeks prior to the first dose CLN-978

  7. Investigational or standard of care monoclonal antibodies, chemotherapy, or other investigational agent ≤ 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of CLN-978

  8. Radiation therapy (XRT), with the exception of focal treatment for symptom control, ≤ 4 weeks of the first dose of CLN-978

  • Woman of child-bearing potential who is pregnant, breast-feeding, or plans to become pregnant

  • Male patients who plan to father a child or donate sperm within 120 days of last study drug administration

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Alabama at Birmingham Birmingham Alabama United States 35294
2 City of Hope Duarte California United States 91010
3 Winship Cancer Institute at Emory University Atlanta Georgia United States 30322
4 Massachusetts General Hospital Boston Massachusetts United States 02114
5 University of Texas Southwestern Medical Center Dallas Texas United States 75390

Sponsors and Collaborators

  • Cullinan Oncology, LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Cullinan Oncology, LLC
ClinicalTrials.gov Identifier:
NCT05879744
Other Study ID Numbers:
  • CLN-978-001
First Posted:
May 30, 2023
Last Update Posted:
Jun 1, 2023
Last Verified:
May 1, 2023
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Cullinan Oncology, LLC
Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell

Study Results

No Results Posted as of Jun 1, 2023