CELTIC-1: A Phase 2B Study of Cerdulatinib in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL)

NCT04021082 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 18-604
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, multinational study of cerdulatinib in patients with relapsed/refractory PTCL dosed with cerdulatinb, designed to (1) Evaluate tumor response, (2) Assess the safety and tolerability of cerdulatinib, (3) Evaluate duration of response (DUR), progression free survival (PFS) and overall survival(OS), (4) Determine the PK properties of cerdulatinib, (5) Evaluate the efficacy endpoints based on Lugano criteria per IRC and (6)To assess the relationship between target expression (e.g., spleen tyrosine kinase \[SYK\], Janus kinase \[JAK\]) and relevant anomalies (e.g., SYK-ITK translocation, mutations in the JAK/STAT pathway) with clinical response.

Conditions

Peripheral T-Cell Lymphoma (PTCL NOS); Nodal Lymphomas of T Follicular Helper (TFH); Follicular T-cell Lymphoma (FTCL); AITL; ALCL; HSTCL; EATL I,II; MEITL, EATL Type II; Nasal Lymphoma

Keywords

Non-Hodgkin's Lymphoma; T-Cell Leukemia; Peripheral T-Cell Lymphoma; Nodal; PTCL; Angioimmunoblastic; AITL; Anaplastic; ALCL; EATL; Follicular; FTCL; hepatosplenic; HSTCL; TFL; SYK; JAK/STAT

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR is defined as the percentage (%) of participants with a complete response (CR), or partial response (PR) as assessed by IRC per RECIL criteria.

  Up to 36 months

Secondary Outcomes (4)

• Complete response (CR)

  Up to 36 months

• Duration of response (DOR)

  Up to 36 months

• Progression-free survival (PFS)

  Up to 36 months

• Overall survival (OS)

  Up to 36 months

Study Arms (4)

Cohort A

EXPERIMENTAL

Cerdulatinib dosing of patients with Peripherial T-Cell Lymphoma (PTCL) not otherwise specified (NOS); Cerdulatinib 30 mg orally (PO) twice daily (BID) (60 mg daily total)

Drug: Cerdulatinib

Cohort B

EXPERIMENTAL

Cerdulatinb dosing of patients with nodal lymphomas of T follicular helper (TFH) phenotype origin, including angioimmunoblastic T cell lymphoma (AITL), follicular T-cell lymphoma (FTCL), and nodal PTCL with TFH phenotype; Cerdulatinib 30 mg orally (PO) twice daily (BID) (60 mg daily total)

Drug: Cerdulatinib

Cohort C

EXPERIMENTAL

Cerdulatinb dosing of patients with Anaplastic large cell lymphoma (ALCL) (anaplastic lymphoma kinase positive \[ALK+\] and negative \[ALK-\]); Cerdulatinib 30 mg orally (PO) twice daily (BID) (60 mg daily total)

Drug: Cerdulatinib

Cohort D

EXPERIMENTAL

Other rare types of extranodal non-cutaneous aggressive PTCL, including hepatosplenic T-cell lymphoma (HSTCL), enteropathy-associated T-cell lymphoma (EATL type I), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL, EATL type II), and extranodal NK/T-cell lymphoma (nasal type); Cerdulatinib 30 mg orally (PO) twice daily (BID) (60 mg daily total)

Drug: Cerdulatinib

Interventions

Cerdulatinib DRUG

Small molecule SYK/JAK kinase inhibitor in development for treatment of hematological malignancies

Cohort A; Cohort B; Cohort C; Cohort D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to give informed consent.
• A histologically confirmed diagnosis, per the WHO 2016 classification \[45\], of any PTCL subtype listed for study. Patients may be entered on the basis of local pathology. Local pathology slides must be available for central pathology review.
• Prior therapy consisting of at least one systemic regimen that involved at least two cycles of treatment.
• In patients with ALCL, prior treatment with brentuximab vendotin unless, in the judgment of the Investigator, such treatment was otherwise contraindicated.
• Relapsed/refractory disease after prior therapy:
• Refractory is defined as progression during treatment or recurrence/progression of disease within ≤ 6 months of completing a treatment regimen that resulted in either SD, a PR, or a CR.
• Relapse is defined as progression or recurrence of disease after a prior documented response (CR or PR) and \> 6 months since last treatment.
• Age ≥ 18 years.
• A life expectancy of \> 3 months.
• An Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Adequate bone marrow reserve, defined as an ANC ≥ 1,000/µL and a platelet count ≥ 75,000/µL. The ANC must be without growth factor support for 7 days, and the platelet count must be without transfusion support within 7 days of study drug initiation. Patients with evidence of marrow involvement must have a platelet count ≥ 50,000/μL.
• NOTE: There are no limits on ANC or platelet count for patients with HSTCL as long as cytopenia, if present, is secondary to disease.
• Adequate renal function, defined as a creatinine clearance of ≥ 30 mL/min calculated using the Cockcroft-Gault equation or based on a 24-hour urine specimen.
• Adequate hepatic function, defined as: i) a serum bilirubin level ≤ 1.5 × ULN; and ii) serum AST/ALT levels ≤ 2.5 × the ULN for the reference lab. A serum bilirubin level ≤ 2.5 mg/dL is permissible if it is clearly due to Gilbert's syndrome. In patients with lymphoma and documented hepatic involvement, adequate hepatic function is defined as: i) total bilirubin level ≤ 2 × ULN; and ii) AST/ALT levels ≤ 3 × ULN.
• Measurable disease for a given tumor type, defined as the presence of ≥ 1 lesion measurable per RECIL criteria (≥ 15 mm) as assessed by CT or, in patients with nodal or mass lesions, by CT/PET.

You may not qualify if:

• A diagnosis of any one of the following PTCL subtypes: (i) primary cutaneous T-cell lymphoma, including primary cutaneous ALCL and primary cutaneous gamma-delta lymphoma; (ii) mycosis fungoides, including that with large-cell transformation; (iii) Sézary syndrome; and (iv) leukemic forms of PTCL (e.g., adult T cell leukemia/lymphoma, T cell prolymphocytic leukemia, T-cell large granular lymphocyte leukemia, aggressive NK leukemia).
• Allogeneic or autologous stem cell transplantation within 90 days of study drug initiation or active immunosuppressive therapy for graft-versus-host disease (GVHD) or GVHD prophylaxis within 8 weeks of study drug initiation.
• Prior cancer therapy with an SYK or JAK inhibitor.
• The need for chronic treatment with a strong inhibitor, sensitive substrate, or inducer of CYP3A4.
• Known active lymphoma involvement of the central nervous system.
• Persistent unresolved toxicity associated with prior treatment that is of Grade ≥ 2 severity (per v5.0 of the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\]) and is also clinically significant in the judgement of the Investigator. Exceptions are alopecia, erectile impotence, hot flashes, diminished libido, and neuropathy.
• Other treatment for the PTCL subtype within 3 weeks of study drug initiation.
• Known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) or known HBV or HCV carrier status.
• Active infection requiring systemic treatment, defined as the need for intravenous antimicrobial, antifungal, or antiviral agents.
• Clinically significant cardiac disease, defined by any of the following:
• A history of clinically significant cardiac disease or congestive heart failure (New York Heart Association Class II). Patients must not have unstable angina (anginal symptoms at rest) or new-onset angina within the last 90 days or myocardial infarction (MI) within the past 6 months.
• Clinically significant cardiac arrhythmias, defined as requiring anti-arrhythmic therapy (excluding beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
• Congenital long QT syndrome or concomitant medications known to prolong the QT interval except those required for infections that carry a low risk of QTc prolongation.
• A Fridericia-corrected QT interval of ≥ 450 msec (males) or ≥ 470 msec (females) at screening.
• Difficulty swallowing or malabsorption syndrome.

Sponsors & Collaborators

• Portola Pharmaceuticals: lead

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral; Lymphoma, Non-Hodgkin; Leukemia, T-Cell

Interventions

4-(cyclopropylamino)-2-((4-(4-(ethylsulfonyl)piperazin-1-yl)phenyl)amino)pyrimidine-5-carboxamide

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: July 16, 2019
• Study Start: November 15, 2019
• Primary Completion: December 31, 2022
• Study Completion: June 1, 2023
• Last Updated: February 21, 2023

Record last verified: 2020-03