Testing the Effectiveness of the Anti-cancer Drug, Mirdametinib, in Treating Relapsed, Refractory Chronic Lymphocytic Leukemia

NCT07061951 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2025-0463710708UM1CA186709
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

Brief Summary

This phase II trial tests the effect of mirdametinib in treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Mirdametinib, a methyl ethyl ketone (MEK) inhibitor, works by blocking the action of an abnormal protein that signals cancer cells to multiply. This may help slow or stop the spread of cancer cells. Giving mirdametinib may be effective in treating patients with relapsed or refractory CLL or SLL.

Conditions

Recurrent Small Lymphocytic Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Refractory Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Best objective response rate

  Will be defined as the best achieved response (e.g., complete response \[CR\], CR with incomplete marrow recovery, partial remission \[PR\], PR with lymphocytosis) as determined by International Workshop on Chronic Lymphocytic Leukemia criteria. Will be summarized descriptively.

  Up to 5 years

Secondary Outcomes (6)

• Progression-free survival (PFS)

  Up to 5 years

• Duration of response

  Up to 5 years

• Overall survival

  Up to 5 years

• Incidence of adverse events (AEs)

  Up to 30 days after last dose of study treatment

• Incidence of high grade (3+) AEs

  Up to 30 days after last dose of study treatment

Study Arms (1)

Treatment (mirdametinib)

EXPERIMENTAL

Patients receive mirdametinib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo bone marrow biopsy, blood sample collection, echocardiography, and CT throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Echocardiography Test; Drug: Mirdametinib

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (mirdametinib)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (mirdametinib)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (mirdametinib)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC, Echocardiography

Treatment (mirdametinib)

Mirdametinib DRUG

Given PO

Also known as: Gomekli, MEK Inhibitor PD0325901, PD 901, PD-0325901

Treatment (mirdametinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed CLL or small lymphocytic lymphoma (SLL), as documented by a history at some point in time of an absolute peripheral blood B cell count \> 5000/mcL with a monoclonal B cell population coexpressing CD19, CD5, and CD23, or if CD23 negative, then documentation of the absence of t(11;14) or cyclin D1 overexpression. Alternatively, patients with lymphadenopathy in the absence of circulating disease will also be eligible for this study if lymph node biopsy or bone marrow biopsy has established the diagnosis of CLL with the above immunophenotype
• Patients must have a current indication for treatment as defined by the iwCLL 2018 Guidelines (Hallek et al., 2018):
• Massive or progressive splenomegaly; OR
• Massive lymph nodes, nodal clusters, or progressive lymphadenopathy; OR
• Grade 2 or 3 fatigue; OR
• Fever ≥ 100.5°F or night sweats for greater than 2 weeks without documented infection; OR
• Presence of weight loss ≥ 10% over the preceding 6 months; OR
• Progressive lymphocytosis with an increase of ≥ 50% over a 2-month period or an anticipated doubling time of less than 6 months; OR
• Evidence of progressive marrow failure as manifested by the development of or worsening of anemia and or thrombocytopenia
• Patients must have measurable disease, defined as lymphocytosis \> 5,000/mcL, palpable or computed tomography (CT) measurable lymphadenopathy \> 1.5 cm, or bone marrow involvement \> 30%
• Patients must have received at least two prior therapies for CLL including systemic therapy containing a Bruton's tyrosine kinase (BTK) inhibitor and a BCL2 inhibitor. Patients are required to have prior BTK inhibitor-based therapy because constitutive extracellular signal-regulated kinase (ERK) activation is seen in all patients with progression after BTK inhibitor therapy
• Age ≥ 18 years. Because CLL is extremely rare in persons \< 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
• Absolute neutrophil count ≥ 500/mcL. Growth factor is allowed to achieve this level. Neutrophil count of 250 is permitted for patients with bone marrow involvement
• Unless they have significant bone marrow involvement of CLL confirmed on biopsy

You may not qualify if:

• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to mirdametinib
• Patients with concurrent administration of strong inhibitors and inducers of P-glycoprotein (P-g)p or breast cancer specific resistance protein (BCRP). If discontinuation of the medication is appropriate, a washout duration of approximately 3 to 5 half-lives is recommended prior to the first dose of mirdametinib
• Patients with concurrent administration of strong CYP3A4 inducers. If discontinuation of the medication is appropriate, a washout duration of approximately 3 to 5 half-lives is recommended prior to the first dose of mirdametinib
• Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
• Pregnant women are excluded from this study because mirdametinib is MEK inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother mirdametinib, breastfeeding should be discontinued if the mother is treated with mirdametinib
• Patients with active infection requiring intravenous (IV) antibiotics
• History or current evidence of glaucoma or clinically significant abnormalities on the ophthalmological exam, including but not limited to cataract limiting the ability to examine the retina or any optical coherence tomography (OCT) finding that could be a significant risk factor for retinal vein occlusion (RVO), retinopathy, or neovascular macular degeneration
• Patients with corrected QT (QTc) \> 470 ms

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

RECRUITING

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Specimen Handling; Biopsy; mirdametinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Jennifer R Brown

  Dana-Farber - Harvard Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2025
• First Posted: July 14, 2025
• Study Start (Estimated): September 8, 2026
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2030
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (4)