What side effects are associated with this type of intervention?

Common treatments for Chronic Lymphocytic Leukemia (CLL) include targeted agents and hematopoietic cell transplantation (HCT). Targeted agents, which may be similar to the selective PKC-β inhibitor MS-553, often cause side effects such as infections, fatigue, gastrointestinal issues, and cardiovascular events. Nonmyeloablative HCT can lead to chronic graft-versus-host disease (GVHD) and nonrelapse mortality, while myeloablative HCT is associated with high treatment-related morbidity and mortality. Autologous HCT, though rarely performed, can impair quality of life without improving overall survival.

What prior FDA approvals exist?

The FDA has approved several treatments for Chronic Lymphocytic Leukemia (CLL), including targeted therapies and immunotherapies. Notable approvals include ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, and venetoclax, a BCL-2 inhibitor, both of which have shown significant efficacy in CLL. Additionally, monoclonal antibodies such as obinutuzumab and rituximab have been approved for use in combination with other therapies. While specific information on selective PKC-β inhibitors like MS-553 is limited, these approved treatments share a common goal of targeting specific pathways to manage CLL effectively.

What other types of research exist?

Promising novel alternatives to MS-553 for CLL patients include: 1) BTK inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib, which are oral therapies given continuously until progression. 2) Venetoclax, a BCL2 inhibitor, often used in combination with obinutuzumab for a fixed duration. 3) PI3Kδ-specific inhibitors like CAL-101 (GS-1101), which have shown clinical activity against CLL. These treatments have demonstrated efficacy in clinical trials and are viable options for CLL patients in 2024.

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Protein Kinase Inhibitor

MS-553 for Chronic Lymphocytic Leukemia

Phase 1 & 2

Waitlist Available

Research Sponsored by MingSight Pharmaceuticals, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age 18 years or older

Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL): History of histologically documented CLL or SLL that meets IWCLL diagnostic criteria according to the 2008 guidelines, and Indication for treatment as defined by the 2008 IWCLL guidelines, or the need for disease reduction prior to allogeneic transplantation

Must not have

Active and uncontrolled autoimmune cytopenia(s)

Any of the following prior therapies within 14 days prior to cycle 1, day 1: Major surgery, 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, 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)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up cycle 1 day1, cycle 1 day 8, (each cycle is 28 days)

Awards & highlights

Approved for 5 Other Conditions

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial is testing a new drug called MS-553, which blocks a protein that helps cancer cells grow. It is aimed at patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma. By blocking this protein, the drug hopes to stop the cancer from growing and help patients who do not respond well to other treatments.

Who is the study for?

This trial is for adults over 18 with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), who meet specific medical guidelines and need treatment. People can't join if they've had major surgery recently, have transformed CLL/SLL, uncontrolled autoimmune issues, or used certain therapies within the last two weeks.

What is being tested?

The study tests MS-553's safety and effectiveness in different doses for patients with CLL/SLL. It will be combined with other drugs like venetoclax, Rituximab, obinutuzumab, and acalabrutinib to see how well it works.

What are the potential side effects?

Possible side effects of MS-553 may include reactions at the infusion site, fatigue, nausea. The other medications used can also cause immune system reactions, infections due to low blood cell counts, bleeding problems and heart rhythm changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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I have been diagnosed with CLL or SLL and need treatment according to 2008 guidelines.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have an active autoimmune condition affecting my blood cells.

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I haven't had major surgery, high-dose steroids, or certain cancer treatments in the last 14 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ cycle 1 day1, cycle 1 day 8, (each cycle is 28 days)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~cycle 1 day1, cycle 1 day 8, (each cycle is 28 days)

This trial's timeline: 3 weeks for screening, Varies for treatment, and cycle 1 day1, cycle 1 day 8, (each cycle is 28 days) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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.

Secondary study objectives

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.

Other study objectives

Pharmacokinetic (PK) parameters of MS-553

Awards & Highlights

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

8Treatment groups

Experimental Treatment

Group I: Phase II Expansion Cohort B3Experimental Treatment2 Interventions

BTK inhibitor naïve CLL/SLL patients with certain gene mutations

Group II: Phase II Expansion Cohort B2Experimental Treatment2 Interventions

BTK inhibitor naïve CLL/SLL patients

Group III: Phase II Expansion Cohort A3 (MS-553 Monotherapy)Experimental Treatment1 Intervention

patients with aggressive lymphoma

Group IV: Phase II Expansion Cohort A2 (MS-553 Monotherapy)Experimental Treatment1 Intervention

R/R CLL/SLL patients

Group V: Phase I Dose Escalation Cohort A1 (MS-553 Monotherapy)Experimental Treatment1 Intervention

R/R CLL/SLL patients

Group VI: Phase I Combination Dose Escalation Cohort C1Experimental Treatment4 Interventions

Bcl-2 inhibitor naïve CLL/SLL patients

Group VII: Phase I Combination Dose Escalation Cohort B1Experimental Treatment2 Interventions

BTK inhibitor naïve CLL/SLL patients

Group VIII: Experimental: Phase II Expansion Cohort C2Experimental Treatment4 Interventions

Bcl-2 inhibitor naïve CLL/SLL patients

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

MS-553

2015

Completed Phase 1

~40

Venetoclax

FDA approved

Rituximab

FDA approved

Obinutuzumab

FDA approved

Acalabrutinib

FDA approved

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Chronic Lymphocytic Leukemia (CLL) include BTK inhibitors (e.g., ibrutinib, acalabrutinib), BCL2 inhibitors (e.g., venetoclax), and emerging therapies like PKC-β inhibitors (e.g., MS-553). BTK inhibitors block Bruton's tyrosine kinase, a key enzyme in the B-cell receptor signaling pathway, thereby inhibiting CLL cell proliferation and survival. BCL2 inhibitors promote apoptosis in CLL cells by targeting the BCL2 protein, which prevents programmed cell death. PKC-β inhibitors, such as MS-553, selectively inhibit protein kinase C-beta, which plays a role in cell survival and proliferation. These targeted therapies are crucial for CLL patients as they offer more precise treatment options with potentially fewer side effects compared to traditional chemotherapy, improving both survival rates and quality of life.

New angles of attack in the fight against chronic lymphocytic leukemia: the advent of novel non-chemotherapeutic agents.