A Study to Investigate the Efficacy and Safety of MS-553 in CLL/SLL

Study Overview
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Brief Summary
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This is a Phase I/II, single arm, multi-center, open-label clinical trial of MS-553 in patients with CLL/SLL whose disease relapsed after or was refractory to at lease 1 prior therapy (chemotherapy and/or targeted drug therapy, which must include BTK inhibitor therapy) and who are indicated for treatment per IWCLL2018.

Official Title
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A Phase I/II Study to Investigate the Efficacy and Safety of MS-553 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Conditions
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Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Intervention / Treatment
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* Drug: MS-553


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older, male or female. Diagnosis of CLL/SLL per IWCLL2018 criteria. Patients with relapsed or refractory CLL/SLL who have failed at least 1 prior therapy (chemotherapy and/or targeted drug therapy, which must include BTK inhibitor therapy), are indicated for treatment per IWCLL2018. Measurable lesions detected by contrast-enhanced computed tomography (CT): at least one lymph node with a maximum axis of more than 1.5 cm and one measurable vertical dimension. WHO/ECOG performance status of 0 to 2. Patients with an estimated survival of more than 3 months. Exclusion Criteria: Biopsy-proven and pathologically confirmed current or past transformation to Richter's syndrome. Patients with active and uncontrolled autoimmune cytopenia, including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura. Patients who have received any of the following treatments within 14 days prior to the first dose: Major surgery; Glucocorticoids (at a dose equal to or greater than 20 mg/day prednisone or equivalent), unless used by inhalation, topical or intraarticular route, or unless necessary for premedication before and after iodinated contrast dye. After discussion with the Sponsor, steroid therapy at high doses for an extended period may be allowed under the following circumstances: Treatment of autoimmune hemolysis or autoimmune thrombocytopenia associated with CLL/SLL; Short-term (within 14 days) use to treat inactive infections of diseases unrelated to CLL/SLL (e.g. arthritis, asthma), which results in acute exacerbation, including steroid dose modifications required for adrenal insufficiency; Cytotoxic chemotherapy or biologic therapy, excepting BCR pathway kinase inhibitors for which a washout of 24 hours prior to the first dose is required. Toxicity from prior anti-tumor therapy (chemotherapy, radiotherapy, or biotherapy) did not restore to ≤ Grade 1 (except for alopecia); atrial fibrillation from prior treatment with BTK inhibitors did not restore to ≤ Grade 2. Central nervous system (CNS) leukemia or lymphoma, including a history of asymptomatic, previously treated CNS disease.

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
Interventional Model Description: Stage 1 3+3 dose escalation study with expansion to Stage 2
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MS-553 Low Dose<br>MS-553 Low Dose PO BID | Drug: MS-553<br>* MS-553<br>|
| Experimental: MS-553 Mid Dose-1<br>MS-553 Mid Dose-1 PO BID | Drug: MS-553<br>* MS-553<br>|
| Experimental: MS-553 Mid Dose-2<br>MS-553 Mid Dose-2 PO BID | Drug: MS-553<br>* MS-553<br>|
| Experimental: MS-553 High Dose<br>MS-553 High Dose PO BID | Drug: MS-553<br>* MS-553<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting toxicities |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events |  | Assessed throughout the study from the time of first dose of study drug until 30 days after the patient's last dose of study drug or until the event has resolved, stabilized, or an outcome reached, whichever comes first regardless of timing of EoT visit | 
| Overall response rate |  | up to 24 months | 
| Time to tumor response |  | During intervention | 
| Disease control rate |  | During intervention | 
| Progression free survival |  | During intervention | 
| Overall survival |  | During intervention | 
| Assessment of minimal residual disease |  | During intervention |