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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03492125
Recruitment Status : Recruiting
First Posted : April 10, 2018
Last Update Posted : March 15, 2023
Sponsor:
Information provided by (Responsible Party):
MingSight Pharmaceuticals, Inc

Study Description
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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

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Aggressive Lymphoma Drug: MS-553 Drug: acalabrutinib Drug: venetoclax Drug: Rituximab Drug: obinutuzumab Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 117 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: a limited 3+3 phase 1 dose escalation study with expansion cohorts
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 25, 2018
Estimated Primary Completion Date : April 15, 2024
Estimated Study Completion Date : June 15, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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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
Experimental: Phase II Expansion Cohort A2 (MS-553 Monotherapy)
R/R CLL/SLL patients
 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 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: acalabrutinib
Oral
Experimental: Phase II Expansion Cohort B2
BTK inhibitor naïve CLL/SLL patients
 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 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: MS-553
Oral, multiple dose levels

Drug: venetoclax
Oral
Other Names:
  • Venclexta
  • Venclyxto

Drug: Rituximab
IV
Other Names:
  • Rituxan
  • MabThera

Drug: obinutuzumab
IV
Other Name: Gazyva
Experimental: Experimental: Phase II Expansion Cohort C2
Bcl-2 inhibitor naïve CLL/SLL patients
 Drug: MS-553
Oral recommended phase 2 dose of MS-553

Drug: venetoclax
Oral
Other Names:
  • Venclexta
  • Venclyxto

Drug: Rituximab
IV
Other Names:
  • Rituxan
  • MabThera

Drug: obinutuzumab
IV
Other Name: Gazyva


Outcome Measures
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Primary Outcome Measures :
  1. 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. [ Time Frame: 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 ]
    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 :
  1. 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. [ Time Frame: 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.


Other Outcome Measures:
  1. Pharmacokinetic (PK) parameters of MS-553 [ Time Frame: Time Frame: Cycle 1 day1, Cycle 1 Day 8, Cycle 2 Day 1(each cycle is 28 days) ]
    Evaluate Cmax

  2. Pharmacokinetic (PK) parameters of MS-553 [ Time Frame: Cycle 1 day 1, Cycle 1 Day 8 (each cycle is 28 days) ]
    Evaluate Tmax

  3. Pharmacokinetic (PK) parameters of MS-553 [ Time Frame: Cycle 1 Day 1, Cyle 1 Day 8 (each cycle is 28 days) ]
    Evaluate t1/2

  4. Pharmacokinetic (PK) parameters of MS-553 [ Time Frame: Cycle 1 day1, Cycle 1 Day 8, (each cycle is 28 days) ]
    Evaluate AUC (0-24; 0-∞)

  5. 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 [ Time Frame: C1D1 Pre-dose and C1D8 pre dose and 3 hours post dose ]
  6. Evaluate pharmacogenomic biomarkers in patients with CLL/SLL treated with MS-553 to compare germline DNA with tumor DNA via changes in sequence analysis [ Time Frame: C1D1 and the 1st day of each cycle and end of treatment (each cycle is 28 days) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03492125


Contacts
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Contact: Kai Zhang 858-699-7681 kzhang@mingsight.com
Contact: Gerald Messerschmidt, MD 610-613-3882

Locations
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United States, Michigan
University Of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Roxana Taralunga    734-232-0773    roxanat@med.umich.edu   
Principal Investigator: Christine Ye, MD         
United States, New York
Columbia University, Herbert Irving Comprehensive Cancer Center Recruiting
New York, New York, United States, 10032
Contact: Emma Bentley-Hicks    212-304-5558    eb3416@cumc.columbia.edu   
Principal Investigator: Nicole Lamanna, MD         
United States, Ohio
The Ohio State University, James Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Lindsey Rike    614-685-6559    Lindsey.Rike@osumc.edu   
Principal Investigator: James Blachly, MD         
United States, Texas
MD Anderson Cancer Center, Department of Leukemia Recruiting
Houston, Texas, United States, 77030
Contact: Sheri Allred    713-792-2882    slallred@mdanderson.org   
Principal Investigator: Nitin Jain, MD         
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: McKell Reese    801-587-4775    McKell.Reese@hsc.utah.edu   
Principal Investigator: Deborah Stephens, MD         
Sponsors and Collaborators
MingSight Pharmaceuticals, Inc
More Information
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Responsible Party: MingSight Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT03492125    
Other Study ID Numbers: MS-553-103
First Posted: April 10, 2018    Key Record Dates
Last Update Posted: March 15, 2023
Last Verified: November 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Chronic Disease
 Disease Attributes
Pathologic Processes
Rituximab
Obinutuzumab
Venetoclax
Acalabrutinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents