Study of Safety,Efficacy and Pharmacokinetics of CT-1530 in Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia

Study Overview
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Brief Summary
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This is a phase I study of BTK inhibitor CT-1530 in patients with relapsed or refractory B cell non-Hodgkin lymphoma (B-NHL), chronic lymphocytic leukemia (CLL) or Waldenstrom's macroglobulinemia (WM). The purpose of the study is to determine the MTD/RP2D of CT-1530, and evaluate its safety and tolerability as monotherapy in subjects with relapsed or refractory B cell non-Hodgkin lymphoma (B-NHL), chronic lymphocytic leukemia (CLL) or Waldenstrom's macroglobulinemia (WM).

Official Title
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Study of Safety, Efficacy and Pharmacokinetics of CT-1530 in Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia

Conditions
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Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Waldenstrom's Macroglobulinemia, Mantle Zone Lymphoma Refractory/Recurrent, Follicle Centre Lymphoma Diffuse, Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Drug: CT-1530


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of B cell Non-Hodgkin Lymphoma(according to World Health Organization [WHO] classification)including Chronic Lymphocytic Leukemia/Small cell Lymphocytic Leukemia (International Workshop),or Waldenstrom's Macroglobulinemia(Second International Workshop). Have failed ≥1 previous treatment for B-NHL/CLL/WM, and have relapsed or refractory disease following last prior treatment. Eastern Cooperative Oncology Group performance status of ≤ 1 and a life expectancy of at least 3 months. Measurable disease as per RECIST v1.1 Availability of tumor sample Adequate hematologic function, as defined by neutrophils ≥ 1.0 x 10^9/L and platelets ≥ 50 x 10^9/L; patients with neutrophils < 1.0 x 10^9/L due to marrow infiltration are allowed to receive growth factors to bring pre-treatment neutrophils to ≥ 1.0 x 10^9/L. Adequate renal function, as defined by creatinine clearance of ≥ 50 ml/min (as estimated by the Cockcroft-Gault equation or as measured by nuclear medicine scan or 24 hour urine collection). Adequate liver function, as defined by AST and ALT ≤ 3 x ULN, and bilirubin ≤ 1.5 x ULN (unless documented Gilbert's syndrome). Exclusion Criteria: Prior allogeneic bone marrow transplant Autologous stem cell transplant within 3 months of screening Active central nervous system involvement Subjects with autoimmune hemolytic anemia or immune thrombocytopenia Prior treatment with a Btk inhibitor Active uncontrolled infection History of malabsorption Uncontrolled illness, i.e cardiac, endocrine, respiratory, etc. History of myocardial infarction, acute coronary syndromes, coronary angioplasty and/or stenting with in the previous 6 months History of another currently active cancer History of major surgery within 4 weeks or minor surgery within 1 week Other medical or psychiatric illness or organ dysfunction HIV positive Positive for Hepatitis B surface antigen or Hepatitis C-virus Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CT-1530<br> | Drug: CT-1530<br>* Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Waldenstrom's Macroglobulinemia, FL, Diffuse B-cell lymphoma, Mental-cell lymphoma<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of dose limiting toxicities (DLTs) during the first cycle of treatment (Phase I) | Maximum Tolerated Dose(s) (MTD(s)) and/or recommended phase 2 dose (RP2D(s)) of CT-1530 in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Mental-cell lymphoma, Diffuse large B-cell lymphoma, FL and Waldenstrom's Macroglobulinemia | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) - Phase I | Preliminary measure of anti-tumor activity of CT-1530 | Up to 24 month | 
| Progression free survival (PFS) per RECIST v1.1 - Phase I | Preliminary measures of anti-tumor activity of CT-1530 | Up to 24 months | 
| Duration of response (DOR) | Preliminary measure of anti-tumor activity of CT-707 | Up to 24 months |