A Dose Escalation Study Evaluating CPI-818 in Relapsed/Refractory T-Cell Lymphoma

Study Overview
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Brief Summary
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This is a Phase 1/1b, open-label, first in human study of CPI-818, an oral interleukin-2-inducible tyrosine kinase (ITK) inhibitor for the treatment of relapsed/refractory (R/R) T-cell lymphoma.. This trial will study the safety, tolerability, and anti-tumor activity of CPI-818 as a single drug.

Detailed Description
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This is a Phase 1/1b, open-label, first in human study of CPI-818, an oral interleukin-2-inducible tyrosine kinase (ITK) inhibitor for the treatment of relapsed/refractory (R/R) T-cell lymphoma.. This trial will study the safety, tolerability, and anti-tumor activity of CPI-818 as a single drug. This trial is composed of dose escalation and dose expansion cohorts.

Official Title
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A Phase 1/1b Dose-Escalation Trial Evaluating CPI-818, an Oral Interleukin-2-Inducible T-Cell Kinase Inhibitor, in Subjects With Relapsed/Refractory T-Cell Lymphoma

Conditions
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T-cell Lymphoma

Intervention / Treatment
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* Drug: CPI-818


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects age ≥18 years Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Histologically confirmed evidence of T-cell lymphoma Measurable disease. Adequate organ function. At least 2 standard therapies for advanced or recurrent disease or had a disease for which there is no more than one established therapy. Exclusion Criteria: Treatment with systemic immunosuppressive medication. History of allogeneic hematopoietic stem cell transplantation. History of primary immunodeficiency, solid organ transplantation. History of opportunistic infection within 180 days of starting study drug. Females who are pregnant, lactating, or intend to become pregnant History of invasive prior malignancy that required systemic therapy within last 3 years. Concomitant use of strong inhibitors or inducers of CYP3A.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPI-818 Dose Escalation<br>Participants will receive CPI-818 capsule, orally, twice per day at an assigned dose, till disease progression, complete response or remission (CR) for >2 months or if dose determined to be unsafe. | Drug: CPI-818<br>* Interleukin-2 inducible T-cell Kinase Inhibitor<br>|
| Experimental: CPI-818 Dose Expansion phase<br>Participants with different T-cell lymphoma sub-types will receive CPI-818 capsules at the specific dose selected from the Dose escalation phase of the study. CPI-818 capsules at the selected dose will be taken orally, twice per day until disease progression or CR for > 2 months. | Drug: CPI-818<br>* Interleukin-2 inducible T-cell Kinase Inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, nature, and severity of adverse events following treatment with CPI 818 to establish the safety and tolerability with increasing dose |  | First dose until 30 days after treatment stop | 
| Incidence and nature of dose limiting toxicities (DLTs) of CPI 818 to establish either the maximum tolerated dose (MTD) or the maximum administered dose (MAD) of CPI 818 |  | Up to approximately 21 days after first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC) of CPI-818 in blood samples to evaluate the pharmacokinetic profile of CPI 818 |  | Day 1, 2, 8, 15 of Cycle 1, Day 1 and 2 of Cycle 3, and Day 1 for all even number Cycles. Each Cycle is 21 days. | 
| Maximum serum concentration (Cmax) of CPI-818 in blood samples to evaluate the pharmacokinetic profile of CPI 818 |  | Day 1, 2, 8, 15 of Cycle 1, Day 1 and 2 of Cycle 3, and Day 1 for all even number Cycles. Each Cycle is 21 days. | 
| Objective response rate per Laguno Classification for CTCL and Consensus Statement for Response for CTCL to assess the anti-tumor activity of CPI 818 in subjects with R/R T cell lymphoma |  | From start of treatment through end of study treatment, up to approximately 24 months | 
| Evaluate total percentage of tumor gene expression in post-treatment blood and tumor samples to evaluate pharmacodynamic changes with treatment. |  | Day 1, 2, 8, 15 of Cycle 1, Day 1 and 2 of Cycle 3, and Day 1 for all even number Cycles. Each Cycle is 21 days. | 
| Evaluate overall percentage of malignant cells in post-treatment blood and tumor samples to evaluate pharmacodynamic changes with treatment. |  | Day 1, 2, 8, 15 of Cycle 1, Day 1 and 2 of Cycle 3, and Day 1 for all even number Cycles. Each Cycle is 21 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CTCL, PTCL