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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03492125
• Other study ID #: MS-553-103
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 25, 2018
• Est. completion date: June 15, 2024

Study information

• Verified date: November 2022
• Source: MingSight Pharmaceuticals, Inc
• Contact: Kai Zhang
• Phone: 858-699-7681
• Email: kzhang[@]mingsight.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 117
• Est. completion date: June 15, 2024
• Est. primary completion date: April 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Aggressive Lymphoma
• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Small Lymphocytic Lymphoma

Intervention

Drug:
• MS-553
Oral, multiple dose levels
• MS-553
Oral recommended phase 2 dose of MS-553
• acalabrutinib
Oral
• venetoclax
Oral
• Rituximab
IV
• obinutuzumab
IV

Locations

Country	Name	City	State
United States	University Of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	The Ohio State University, James Comprehensive Cancer Center	Columbus	Ohio
United States	MD Anderson Cancer Center, Department of Leukemia	Houston	Texas
United States	Columbia University, Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Huntsman Cancer Institute	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
MingSight Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	Pharmacokinetic (PK) parameters of MS-553	Evaluate Tmax	Cycle 1 day 1, Cycle 1 Day 8 (each cycle is 28 days)
Other	Pharmacokinetic (PK) parameters of MS-553	Evaluate t1/2	Cycle 1 Day 1, Cyle 1 Day 8 (each cycle is 28 days)
Other	Pharmacokinetic (PK) parameters of MS-553	Evaluate AUC (0-24; 0-8)	Cycle 1 day1, Cycle 1 Day 8, (each cycle is 28 days)
Other	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
Other	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)
Primary	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.	The primary endpoint of this study is the incidence rate of dose-limiting toxicities and treatment-emergent adverse events requiring study drug discontinuation	Assessments for DLT and TEAE will occur during cycle 1. The primary endpoint will be the rate of DLT and TEAE requiring study drug discontinuation in the first 28 days
Secondary	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.	This will be assessed according to the International Workshop on Chronic Lymphocytic Leukemia Response Criteria with modifications for treatment-related lymphocytosis.	Screening, post cycle 3 and 6 cycles (each cycle is 28 days)