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

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

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

Study Overview

• Status: Terminated
• Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Aggressive Lymphoma
• Intervention / Treatment: Drug: Rituximab; Drug: MS-553; Drug: MS-553; Drug: acalabrutinib; Drug: venetoclax; Drug: obinutuzumab

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University, Herbert Irving Comprehensive Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University, James Comprehensive Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center, Department of Leukemia
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I Dose Escalation Cohort A1 (MS-553 Monotherapy); R/R CLL/SLL patients	Drug: MS-553; Oral, multiple dose levels; Drug: MS-553; Oral recommended phase 2 dose of MS-553
Experimental: Phase II Expansion Cohort A2 (MS-553 Monotherapy); R/R CLL/SLL patients	Drug: MS-553; Oral, multiple dose levels; Drug: MS-553; Oral recommended phase 2 dose of MS-553
Experimental: Phase II Expansion Cohort A3 (MS-553 Monotherapy); patients with aggressive lymphoma	Drug: MS-553; Oral, multiple dose levels; Drug: MS-553; Oral recommended phase 2 dose of MS-553
Experimental: Phase I Combination Dose Escalation Cohort B1; BTK inhibitor naïve CLL/SLL patients	Drug: MS-553; Oral, multiple dose levels; Drug: MS-553; Oral recommended phase 2 dose of MS-553; Drug: acalabrutinib; Oral
Experimental: Phase II Expansion Cohort B2; BTK inhibitor naïve CLL/SLL patients	Drug: MS-553; Oral, multiple dose levels; Drug: MS-553; Oral recommended phase 2 dose of MS-553; Drug: acalabrutinib; Oral
Experimental: Phase II Expansion Cohort B3; BTK inhibitor naïve CLL/SLL patients with certain gene mutations	Drug: MS-553; Oral, multiple dose levels; Drug: MS-553; Oral recommended phase 2 dose of MS-553; Drug: acalabrutinib; Oral
Experimental: Phase I Combination Dose Escalation Cohort C1; Bcl-2 inhibitor naïve CLL/SLL patients	Drug: Rituximab; IV; Other Names: Rituxan; MabThera; Drug: MS-553; Oral, multiple dose levels; Drug: MS-553; Oral recommended phase 2 dose of MS-553; Drug: venetoclax; Oral; Other Names: Venclexta; Venclyxto; Drug: obinutuzumab; IV; Other Names: Gazyva
Experimental: Experimental: Phase II Expansion Cohort C2; Bcl-2 inhibitor naïve CLL/SLL patients	Drug: Rituximab; IV; Other Names: Rituxan; MabThera; Drug: MS-553; Oral, multiple dose levels; Drug: MS-553; Oral recommended phase 2 dose of MS-553; Drug: venetoclax; Oral; Other Names: Venclexta; Venclyxto; Drug: obinutuzumab; IV; Other Names: Gazyva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Incidence Rate of DLT and TEAE Requiring Study Drug Discontinuation	DLT are defined as any of the following treatment-emergent events occurring during the DLT evaluation period. 1. Death 2. Hematologic toxicities: • Grade 4 neutropenia for ≥ 7 days • Grade 3 febrile neutropenia: absolute neutrophil count (ANC) 38.3°C (101°F) or a sustained temperature ≥38°C (100.4°F) for > 1 hour • Grade 4 thrombocytopenia ≥ 14 days (patients with baseline platelet count of ≥ 50 x 109 /L) • Grade 4 thrombocytopenia ≥ 28 days (patients with baseline platelet count < 50 x 10 9 /L) • ≥ Grade 3 thrombocytopenia associated with ≥ Grade 2 hemorrhage • New ≥ Grade 3 anemia requiring transfusion in a patient previously transfusion independent. 3. Nonhematologic toxicities: • Any other ≥ Grade 3 toxicity not reversed to any one of the following three conditions in 7 days with appropriate intervention: a) baseline; b) < Grade 1; or c) a status considered to be controlled by the SRC. • Any TEAE requiring >25% of doses of scheduled study drug to be withheld during the DLT period	Assessments for DLT and TEAE will occur during Cycle 1 (28 days) for A1 Cohort and B1 Cohort and Cycles 1-4 (up to 112 days) for C1 Cohort.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The ORR of MS-553 in Patients With CLL/SLL Whose Disease Relapsed After or Was Refractory to at Least One Prior Therapy	This will be assessed according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Response Criteria with modifications for treatment-related lymphocytosis. Any patient who receives at least one cycle of study therapy is evaluable for response.	Evaluation of the efficacy endpoints related to response will incorporate the data from the first 9 cycles (up to 252 days) of treatment.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) parameters of MS-553	Evaluate Cmax	Time Frame: Cycle 1 day1, Cycle 1 Day 8, Cycle 2 Day 1(each cycle is 28 days)
Pharmacokinetic (PK) parameters of MS-553	Evaluate Tmax	Cycle 1 day 1, Cycle 1 Day 8 (each cycle is 28 days)
Pharmacokinetic (PK) parameters of MS-553	Evaluate t1/2	Cycle 1 Day 1, Cyle 1 Day 8 (each cycle is 28 days)
Pharmacokinetic (PK) parameters of MS-553	Evaluate AUC (0-24; 0-∞)	Cycle 1 day1, Cycle 1 Day 8, (each cycle is 28 days)
Evaluate pharmacodynamics biomarker,ability of MS-553 to inhibit PKC signaling (phosphorylation of PKC Beta substrate in patients with CLL/SLL treated with MS-553		C1D1 Pre-dose and C1D8 pre dose and 3 hours post dose
Evaluate pharmacogenomic biomarkers in patients with CLL/SLL treated with MS-553 to compare germline DNA with tumor DNA via changes in sequence analysis		C1D1 and the 1st day of each cycle and end of treatment (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: MingSight Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2018
• Primary Completion (Actual): November 28, 2023
• Study Completion (Actual): November 28, 2023

Study Registration Dates

• First Submitted: March 24, 2018
• First Submitted That Met QC Criteria: April 2, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): April 10, 2025
• Last Update Submitted That Met QC Criteria: April 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Lymphoma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Antineoplastic Agents, Immunological; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Rituximab; Acalabrutinib; Venetoclax; Obinutuzumab
• Other Study ID Numbers: MS-553-103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No