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

A Protocol to Assess the Safety, Efficacy, and Pharmacokinetics of Continuous Subcutaneous Administration of Low-dose Lenalidomide (STAR-LLD) for the Treatment of Multiple Myeloma (MM)

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 assess the immunologic activity of natural killer (NK) cells and T cells for innate and humoral immunity.
• To establish the pharmacokinetic (PK) profile of STAR-LLD at a defined infusion rate targeting steady-state blood concentrations.
• To determine pharmacodynamic (PD) changes with STAR-LLD in a panel of biomarkers associated with clinical response to lenalidomide.
• 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
• Immune profiles, functional assays for NK cell activation and antigen specific T-cell activity.
• 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

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Amy Chergey; Phone Number: 949 433 6750; Email: achergey@startontx.com

Study Locations

• United States
  • Ohio
    • Canton, Ohio, United States, 44718
      • Recruiting
      • Gabrail Cancer & Research Center
      • Principal Investigator: Nashat Gabrail, MD
      • Contact: Carrie Smith, RN; Phone Number: 208 330-492-3345; Email: csmith@gabrailcancercenter.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female ≥18 years at the time of informed consent.
2. Autologous stem cell transplant (ASCT) ineligible.
3. SARS -CoV2 virus (COVID)-19 negative.
4. A prior diagnosis of MM as defined by International Myeloma Working Group (IMWG) criteria (Appendix 7).

5. 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.
6. Intended to be treated in 2nd line or greater with lenalidomide, dexamethasone, and a PI.
7. Proteasome inhibitor sensitive defined as progression free for > 6 months from cessation of PI or never received a prior PI.
8. Progression per IMWG criteria on the most recent line of therapy.
9. 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).
10. 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.
11. Able to take anti-thrombotic prophylaxis.

12. The following laboratory results must be met during screening:

    • ANC ≥1,000 cells/mm3 (1.0 x 109/L).
    • Platelet count ≥75,000 cells/mm3 (75 x 109/L).
    • Hemoglobin ≥8.0 g/dL (red blood cell (RBC) transfusions are permitted prior to initiation of study drug if hemoglobin is stable for 72 hours).
    • Total bilirubin ≤1.5 x upper limit of normal (ULN), or patient diagnosed with Gilberts syndrome with a total bilirubin <5.0 x ULN that has been reviewed and approved by the Medical Monitor.
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x ULN.
    • Calculated creatinine clearance ≥60 mL/min. Appendix 4
    • Negative pregnancy test for FCBP (must be obtained within 4-14 days before the initiation of study drug.

13. The following criteria must be met within 72 hours prior to first administration of continuous infusion STAR-LLD:

    • ANC ≥1,000 cells/mm3 (1.0 x 109/L).
    • Platelet count ≥75,000 cells/mm3 (75 x 109/L).
    • Hemoglobin ≥8.0 g/dL (RBC transfusions are permitted prior to initiation of study drug if hemoglobin is stable for 72 hours).
    • Calculated creatinine clearance ≥60 mL/min. Appendix 4
    • Negative pregnancy test for FCBP (must be obtained within 24 hours of first dose of study drug).
14. Able and willing to receive percutaneous ambulatory therapy.
15. Has an in-home care partner willing to receive training from a nurse for assistance with pump management.

Exclusion Criteria:

1. Pregnant or breastfeeding.
2. Received an ASCT.
3. Venous thromboembolism within 12 months of starting treatment on study.
4. Patients with active hepatitis B or C or human immunodeficiency virus (HIV) positive and on active therapy for those viral illnesses.
5. 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.
6. Received a prior treatment line containing lenalidomide and failed to achieve an objective response (CR, VGPR or PR).
7. Discontinued a prior line of treatment due to intolerability to lenalidomide.
8. 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).
9. Concurrent clinically significant amyloidosis or plasma cell leukemia or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes).
10. Known active infection requiring systemic anti-infective treatment (prophylactic treatment is permitted).
11. 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).
12. 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).
13. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study ARM1 - Vld (Velcade-lenalidomide-dexamethasone); Bortezomib SC at 1.3 mg/m2 on Days 1, 8, 15, and 22 of each 28-day cycle Lenalidomide 400 mcg/hr continuously for 28 of 28-day cycle Dexamethasone 40mg orally on Days 1, 8, 15 and 22 of each 28-day cycle (age 75 or over 20 mg.	Drug: Lenalidomide; Low-dose lenalidomide continuous SC infusion (STAR-LDD) in combination with bortezomib and dexamethasone; Other Names: Dexamethasone; Bortezomib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the immunologic activity of natural killer (NK) cells and T cells for innate and humoral immunity.	Measure changes in T cell and NK cell function/exhaustion over the study by flow cytometry	12 months
To establish the pharmacokinetic (PK) profile of STAR-LLD at a defined infusion rate targeting steady-state blood concentrations.	Meaured vs predicted blood concentrations of lenalidomide during the infusion and at steady state	12 months
To determine pharmacodynamic (PD) changes with STAR-LLD in a panel of biomarkers associated with clinical response to lenalidomide.	Evaluate desirable changes in immune cells activity over therapy	12 months
Evaluate changes in efficacy indicators including objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR).	An ORR of 60% is representative of patients being retreated with PI and Len	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the DOR, PFS during treatment	Report the deprived data for these outcomes	18 months

Collaborators and Investigators

• Sponsor: Starton Therapeutics, Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2023
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: September 20, 2023
• First Submitted That Met QC Criteria: October 11, 2023
• First Posted (Actual): October 18, 2023

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide; Bortezomib
• Other Study ID Numbers: STAR LLD MM 023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No