Safety, Efficacy, and Pharmacokinetics of Continuous Subcutaneous Lenalidomide in Multiple Myeloma (MM)

NCT06087653 | Recruiting Phase 1 FDA Drug

• 1 other identifier: STAR LLD MM 023
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

Primary Objective • Assess the safety and tolerability of low-dose lenalidomide administered by continuous subcutaneous (SC) infusion (STAR-LLD) in combination with dexamethasone and a proteasome inhibitor (PI). Secondary Objectives

• • To establish the pharmacokinetic (PK) profile of STAR-LLD at a defined infusion rate targeting steady-state blood concentrations.
• • Evaluate changes in efficacy indicators including objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR). Exploratory Objective
• To assess the impact of STAR-LLD on patient reported symptoms and outcomes. Primary Endpoints
• The grade, frequency, and relationship of treatment-emergent adverse events (TEAEs) including adverse events of special interest (AESIs): (gastrointestinal \[GI\] toxicity, fatigue, hematologic toxicity, rash (non-infusion site).
• The observation of dose-limiting toxicities (DLTs) of STAR-LLD during Cycle 1. Secondary Endpoints
• • Blood concentrations of lenalidomide at on Day 1 and at steady state.
• Changes in biomarkers during treatment.
• Rate of complete response, very good partial response (VGPR), partial response (PR), stable disease (SD), and progressive disease.
• Determination of ORR, PFS, and DOR

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Assess the safety and tolerability of low-dose lenalidomide administered by continuous subcutaneous (SC) infusion (STAR-LLD) in combination with dexamethasone and a proteasome inhibitor (PI).

  Based on the incidence of adverse events associated with the use of the drug

  12 months

Secondary Outcomes (4)

• To assess the immunologic activity of natural killer (NK) cells and T cells for innate and humoral immunity.

  12 months

• To establish the pharmacokinetic (PK) profile of STAR-LLD at a defined infusion rate targeting steady-state blood concentrations.

  12 months

• To determine pharmacodynamic (PD) changes with STAR-LLD in a panel of biomarkers associated with clinical response to lenalidomide.

  12 months

• Evaluate changes in efficacy indicators including objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR).

  12 months

Other Outcomes (1)

• Assess the DOR, PFS during treatment

  18 months

Study Arms (5)

ARM1 - Lenalidomide 400 mcg/h

EXPERIMENTAL

Lenalidomide 400 mcg/hr continuously for 28 of 28-day cycle

Drug: Lenalidomide

Arm2 - Lenalidomide 300 mcg/h

EXPERIMENTAL

Lenalidomide 300 mcg/hr continuously for 28 of 28-day cycle

Drug: Lenalidomide

Arm 3 - Lenalidomide 500 mcg/h

EXPERIMENTAL

Lenalidomide 500 mcg/hr continuously for 28 of 28-day cycle

Drug: Lenalidomide

Arm 4 - Lenalidomide 600 mcg/h

EXPERIMENTAL

Lenalidomide 600 mcg/hr continuously for 28 of 28-day cycle

Drug: Lenalidomide

Arm 5 - Lenalidomide oral capsule control

ACTIVE COMPARATOR

Lenalidomide 25mg/d oral capsules continuously for 28 of 28-day cycle

Drug: Lenalidomide 25 MG Oral Capsule

Interventions

Lenalidomide DRUG

Low-dose lenalidomide continuous SC infusion (STAR-LDD) in combination with bortezomib and dexamethasone

Also known as: bortezamib, dexamethasone

ARM1 - Lenalidomide 400 mcg/h; Arm 3 - Lenalidomide 500 mcg/h; Arm 4 - Lenalidomide 600 mcg/h; Arm2 - Lenalidomide 300 mcg/h

Lenalidomide 25 MG Oral Capsule DRUG

Oral lenalidomide for active control

Arm 5 - Lenalidomide oral capsule control

Eligibility Criteria

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

You may qualify if:

• Male or female ≥18 years at the time of informed consent.
• Autologous stem cell transplant (ASCT) ineligible.
• SARS -CoV2 virus (COVID)-19 negative.
• A prior diagnosis of MM as defined by International Myeloma Working Group (IMWG) criteria (Appendix 7).
• Documented measurable disease following first line therapy defined as:
• Serum monoclonal protein ≥1.0 g/dL by protein electrophoresis.
• ≥200 mg/24 hours of monoclonal protein in the urine on 24-hour electrophoresis.
• Serum free light chain (SFLC) ≥10 mg/dL AND abnormal serum kappa to lambda free light chain (FLC) ratio.
• Intended to be treated in 2nd line or greater with lenalidomide, dexamethasone, and a PI.
• Proteasome inhibitor sensitive defined as progression free for \> 6 months from cessation of PI or never received a prior PI.
• Progression per IMWG criteria on the most recent line of therapy.
• Eastern Cooperative Oncology Group (ECOG-Appendix 1) performance status ≤2 (patients with a performance status of 3 based solely on bone pain secondary to MM may be eligible following consultation and approval by the Medical Monitor).
• Willing to comply with the protocol defined Lenalidomide Pregnancy Risk Minimization Plan for the prevention of pregnancy (Appendix 5). Females of childbearing potential (FCBP) must have a medically supervised negative serum or urine pregnancy test 4-14 days prior to planned start of treatment and again 24 hours prior to initiation of study medication. All FCBP must agree to either commit to continued abstinence from sexual intercourse or begin TWO acceptable methods of birth control AT THE SAME TIME, at least 28 days before receiving the first dose of STAR-LLD. FCBP must also agree to ongoing pregnancy testing. Males must agree to use a latex or synthetic condom during sexual contact with a FCBP from the time of starting study treatment through 28 days after the last dose, even if they have had a vasectomy.
• Able to take anti-thrombotic prophylaxis.
• The following laboratory results must be met during screening:

You may not qualify if:

• Pregnant or breastfeeding.
• Received an ASCT.
• Venous thromboembolism within 12 months of starting treatment on study.
• Patients with active hepatitis B or C or human immunodeficiency virus (HIV) positive and on active therapy for those viral illnesses.
• Currently taking any investigational therapy for the treatment of MM. A 28-day washout prior to Cycle 1 Day 1 is required for any previous investigational therapy.
• Received a prior treatment line containing lenalidomide and failed to achieve an objective response (CR, VGPR or PR).
• Discontinued a prior line of treatment due to intolerability to lenalidomide.
• Concomitant use of strong CYP3A inducers (see https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers#table3-3).
• Concurrent clinically significant amyloidosis or plasma cell leukemia or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes).
• Known active infection requiring systemic anti-infective treatment (prophylactic treatment is permitted).
• Prior malignancies within the previous 3 years, other than previously treated squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix or breast or another malignancy that is considered cured with minimal risk of recurrence (e.g., very low and low risk prostate cancer in active surveillance).
• Prior major surgical procedure or radiation therapy within 4 weeks of the initiation of STAR-LLD (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of STAR-LLD).
• Any other condition that precludes adequate understanding, cooperation, and compliance with study procedures or any condition that could pose a risk to the patient's safety, as per the Investigator's judgment.

Sponsors & Collaborators

• Starton Therapeutics, Inc: lead

Study Sites (2)

Regional Oncology Center

Wilson, North Carolina, 27893, United States

ACTIVE NOT RECRUITING

Gabrail Cancer & Research Center

Canton, Ohio, 44718, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Central Study Contacts

Amy Chergey

CONTACT

949 433 6750; achergey@startontx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose defining study

Study Record Dates

• First Submitted: September 20, 2023
• First Posted: October 18, 2023
• Study Start: October 2, 2023
• Primary Completion: May 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: June 19, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)