T-cell NHL (PTCL or CTCL)
Conditions
Keywords
Neoplasms, Lymphoma, Immune System Diseases, First in Human, Lymphoma, T-Cell, Cutaneous +, Lymphoma, T-Cell, Peripheral, Mycosis fungoides, Sezary Syndrome
Brief summary
The purpose of this study is to determine the safety, tolerability, PK and pharmacodynamics of KK2223 in adult participants with relapsed or refractory peripheral T cell lymphoma (PTCL) or cutaneous T cell lymphoma (CTCL).
Detailed description
This is a Phase 1, multicenter, open-label, non randomized study in participants with relapsed or refractory PTCL or CTCL. This study consists of Part 1 (dose-escalation) and Part 2 (backfill). The purpose of this study is to determine the safety, tolerability, PK and pharmacodynamics of K2223 in r/r T-cell NHL (PTCL or CTCL)
Interventions
DRUGKK2223
Intravenous infusion
Sponsors
Kyowa Kirin, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a sequential design study where participants receive interventions in a stepwise manner. Treatment assignments and doses may be adjusted based on interim safety and efficacy analyses conducted throughout the trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults (≥18 years) with confirmed T-cell lymphoma subtypes: PTCL (including nodal T-follicular helper cell lymphoma, ALCL, PTCL NOS) for Parts 1 and 2; CTCL (mycosis fungoides or Sézary syndrome, stages IIB-IV) for Parts 1 and 2, with specific disease involvement criteria in Part 2. * PTCL participants must have relapsed/refractory/intolerant to ≥1 systemic therapy; CD30+ PTCL must have prior brentuximab vedotin treatment or intolerance, and/or ALK-positive ALCL participants should have previously received crizotinib if indicated (crizotinib administration is applicable to US sites only). CTCL participants must have relapsed/refractory/intolerant to ≥2 systemic therapies. * Availability of tumor tissue (current or archival) is required. * Measurable disease required: nodal/extranodal lesions for PTCL and assessable skin disease for CTCL. * ECOG performance status 0-1; adequate neutrophils (≥1000/µL), platelets (≥75,000/µL), renal function (creatinine clearance ≥60 mL/min), liver function within defined limits, and total bilirubin ≤1.5× ULN (up to 3× ULN with Gilbert's syndrome). * Body weight 40 kg to ≤ 200 kg * Life expectancy ≥3 months. * Negative pregnancy test for females of childbearing potential; contraception required for females and males with partners of childbearing potential during and after treatment. * Restrictions on gamete donation and freezing during and after treatment. * Ability to provide informed consent and comply with study procedures. -
Exclusion criteria
* Recent autologous or allogeneic transplant within 120 days before treatment; active GVHD or ongoing immunosuppression after allogeneic transplant; prior HSCT and with active VOD/SOS * Pregnant or breastfeeding females, or those intending pregnancy. * History of HIV, HBV, or HCV infections generally excluded, except for controlled or resolved cases as defined. * Uncontrolled infections requiring antibiotics, antivirals, or antifungals at screening through treatment start. * Significant medical history or complications within six months prior to enrollment, including advanced congestive heart failure (NYHA Class III or higher), recent unstable angina or myocardial infarction, autoimmune diseases requiring systemic immunosuppressive therapy, active or uncontrolled ocular diseases, Grade 3 or 4 peripheral neuropathy, or other poorly controlled conditions as judged by the investigator (e.g., uncontrolled hypertension, diabetes, or arrhythmias). * Use of other investigational drugs within 14 days or 5 half-lives before treatment. * Steroid use over 10 mg/day prednisone equivalent within 14 days prior, except limited corticosteroid use with specific tapering guidelines; topical steroids allowed under conditions for CTCL. * Major surgery, radiotherapy, chemotherapy, or other anti-cancer treatments within 14 days or 5 half-lives before treatment. * Prior mogamulizumab use within six months before treatment; associated rash must be ruled out if \>6 months. * Known history of Grade ≥ 3 hypersensitivity to mogamulizumab. * Failure to recover from prior non-hematologic toxicities to Grade 0 or 1 (except alopecia and mild neuropathy). * Prolonged QT/QTc interval (e.g., QTcF \>480 ms). * Active second primary malignancies except specified non-exclusionary cases. * CNS involvement. * Any condition that may impair compliance or study completion as judged by the Investigator. * Known hypersensitivity to any excipients in the drug formulation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess the incidence of treatment-emergent adverse events and determine the maximum tolerated dose (MTD) of KK2223 in patients with relapsed or refractory peripheral or cutaneous T cell lymphoma (PTCL/CTCL). | Through study completion, an average of 1.5 years | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 (all 72 potentially treated subjects) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Blood Drug Concentration | Through study completion, an average of 1.5 years | The mean drug concentration in the blood |
| To evaluate the immunogenicity of KK2223. | Through study completion, an average of 1.5 years | Incidence of Anti drug antibodies (ADA) in blood |
| To evaluate the preliminary anti-tumor activity of KK2223 (Investigator assessed). | Through study completion, an average of 1.5 years | % in Overall Response Rate (ORR) |
| Pharmacokinetic Parameter Maximum Blood Concentration (Cmax) | Through study completion, an average of 1.5 years | The maximum drug concentration |
| Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) | Through study completion, an average of 1.5 years | A measure of the overall drug exposure over time |
| Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) | Through study completion, an average of 1.5 years | The time taken to reach the maximum drug concentration |
| Pharmacokinetic Parameter Terminal Half-Life (Thalf) | Through study completion, an average of 1.5 years | The time required for the drug concentration to decrease by 50% |
| Pharmacokinetic Parameter Clearance (CL) | Through study completion, an average of 1.5 years | Rate of drug elimination from the body |
| Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) | Through study completion, an average of 1.5 years | Theoretical volume of distribution at steady state and reflects the extent of drug istribution into tissues |
Countries
Italy, Spain, United States
Contacts
CONTACTKyowa Kirin, Inc.
Outcome results
None listed