A Study Of The Selective PKC-β Inhibitor MS- 553

Phase 1

Terminated

• Conditions: Small Lymphocytic Lymphoma; Aggressive Lymphoma; Chronic Lymphocytic Leukemia
• Interventions: Drug: MS-553; Drug: acalabrutinib; Drug: venetoclax; Drug: Rituximab; Drug: obinutuzumab

• Registration Number: NCT03492125
• Lead Sponsor: MingSight Pharmaceuticals, Inc

Brief Summary

A Phase I/II Dose-Escalation and Expansion Study Of The Selective PKC-Β Inhibitor MS-553 In Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-03-24
• Study First Submitted QC: 2018-04-02
• Study First Posted: 2018-04-10
• Study Start: 2018-05-25
• Primary Completion: 2023-11-28
• Study Completion: 2023-11-28
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-16
• Last Update Posted: 2024-07-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

To be eligible for inclusion in the primary escalation and expansion cohort 1 in this study, patients must meet all of the following criteria:

1. Age 18 years or older

2. Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL):

   1. History of histologically documented CLL or SLL that meets IWCLL diagnostic criteria according to the 2008 guidelines, and
   2. Indication for treatment as defined by the 2008 IWCLL guidelines, or the need for disease reduction prior to allogeneic transplantation

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Exclusion Criteria

Patients who meet any of the following criteria are not eligible for the primary escalation and expansion cohorts of this study:

1. Current or past transformation of CLL/SLL to prolymphocytic leukemia (PLL), non-Hodgkin lymphoma, or Hodgkin lymphoma aggressive lymphoma outlined in the inclusion criteria for the optional cohort.

2. Active and uncontrolled autoimmune cytopenia(s)

3. Any of the following prior therapies within 14 days prior to cycle 1, day 1:

   1. Major surgery
   2. Corticosteroids greater than 20 mg / day prednisone (or equivalent), unless used by inhalation or topical route, or unless necessary for premedication before iodinated contrast dye, or for autoimmune hemolytic anemia
   3. Cytotoxic chemotherapy or biologic therapy, excepting BCR pathway kinase inhibitors for which no wash out is required (but must be stopped before cycle 1 day 1)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Phase I Dose Escalation Cohort A1 (MS-553 Monotherapy)	MS-553	R/R CLL/SLL patients
Phase II Expansion Cohort A2 (MS-553 Monotherapy)	MS-553	R/R CLL/SLL patients
Phase II Expansion Cohort A3 (MS-553 Monotherapy)	MS-553	patients with aggressive lymphoma
Phase I Combination Dose Escalation Cohort B1	MS-553	BTK inhibitor naïve CLL/SLL patients
Phase I Combination Dose Escalation Cohort B1	acalabrutinib	BTK inhibitor naïve CLL/SLL patients
Phase II Expansion Cohort B2	MS-553	BTK inhibitor naïve CLL/SLL patients
Phase II Expansion Cohort B3	MS-553	BTK inhibitor naïve CLL/SLL patients with certain gene mutations
Phase I Combination Dose Escalation Cohort C1	MS-553	Bcl-2 inhibitor naïve CLL/SLL patients
Experimental: Phase II Expansion Cohort C2	MS-553	Bcl-2 inhibitor naïve CLL/SLL patients
Phase II Expansion Cohort B2	acalabrutinib	BTK inhibitor naïve CLL/SLL patients
Phase II Expansion Cohort B3	acalabrutinib	BTK inhibitor naïve CLL/SLL patients with certain gene mutations
Phase I Combination Dose Escalation Cohort C1	obinutuzumab	Bcl-2 inhibitor naïve CLL/SLL patients
Phase I Combination Dose Escalation Cohort C1	venetoclax	Bcl-2 inhibitor naïve CLL/SLL patients
Phase I Combination Dose Escalation Cohort C1	Rituximab	Bcl-2 inhibitor naïve CLL/SLL patients
Experimental: Phase II Expansion Cohort C2	Rituximab	Bcl-2 inhibitor naïve CLL/SLL patients
Experimental: Phase II Expansion Cohort C2	obinutuzumab	Bcl-2 inhibitor naïve CLL/SLL patients
Experimental: Phase II Expansion Cohort C2	venetoclax	Bcl-2 inhibitor naïve CLL/SLL patients

Primary Outcome Measures

Name	Time	Method
The primary objective of this study is to evaluate the safety of MS-553 in patients with CLL/SLL whose disease relapsed after or was refractory to at least one prior therapy.	Assessments for DLT and TEAE will occur during Cycle 1 or the DLT period. The primary endpoint will be the rate of DLT and TEAE requiring study drug discontinuation in Cycle 1 or the DLT period	The primary endpoint of this study is the incidence rate of dose-limiting toxicities and treatment-emergent adverse events requiring study drug discontinuation

Secondary Outcome Measures

Name	Time	Method
To evaluate the clinical activity (i.e. the overall response rate (ORR) of MS-553 in patients with CLL/SLL whose disease relapsed after or was refractory to at least one prior therapy.	Screening, post cycle 3 and 6 cycles (each cycle is 28 days)	This will be assessed according to the International Workshop on Chronic Lymphocytic Leukemia Response Criteria with modifications for treatment-related lymphocytosis.

Trial Locations

Locations (5)

University Of Michigan Comprehensive Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States

Columbia University, Herbert Irving Comprehensive Cancer Center; 🇺🇸 New York, New York, United States

MD Anderson Cancer Center, Department of Leukemia; 🇺🇸 Houston, Texas, United States

Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

The Ohio State University, James Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States