A Study of LB-100 in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS)

A Phase 1b/2 Study Evaluating the Safety and Efficacy of Intravenous LB-100 in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) Who Had Disease Progression or Are Intolerant to Prior Therapy

The purpose of this study is to test the safety and efficacy (benefits) of an investigational drug LB-100, for treatment of myelodysplastic syndromes. LB-100 has previously been administered to patients with various solid tumors. In this study, LB-100 will be administered as an intravenous infusion over 120 minutes. This study will be conducted in 2 phases. In phase Ib, escalating doses of LB-100 will be administered to patients to study the safety and to determine a safe dose of LB-100. In phase 2, patients will be administered LB-100 at the dose that was found to be safe in phase Ib. The efficacy (benefits) and safety of LB-100 will be determined in this phase of the study.

Study Overview

• Status: Unknown
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: LB-100

• Study Type: Interventional
• Enrollment (Anticipated): 47
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • H. Lee Moffitt Cancer Center & Research Institute
      • Contact: Lisa Nardelli; Phone Number: 813-745-4731; Email: Lisa.Nardelli@moffitt.org
      • Principal Investigator: Rami Komrokji, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient has signed the Informed Consent Form (ICF) and is able to comply with protocol requirements.

2. Patient has adequate organ function as defined by the following laboratory values:

   • Creatinine clearance (CrCl) ≥ 60ml/min
   • Total serum bilirubin < 1.5 x Upper Limit of Normal (ULN) or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range only in patients with well documented Gilbert's syndrome or hemolysis or who required regular blood transfusions
   • Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) < 3.0 x ULN
3. Age ≥18 years at the time of signing the informed consent form.
4. Documented diagnosis of MDS or MDS/myeloproliferative neoplasm (MPN) by World Health Organization (WHO) criteria that require treatment due to cytopenias and meet the International Prognostic Scoring System (IPSS) criteria for low or int-1 risk.
5. For non-del(5q) patients, failed prior treatment with at least 2 cycles started of azacitidine or decitabine or lenalidomide defined as no response to treatment, loss of response at any time point while on treatment or within 6 months of treatment discontinuation, or progressive disease/intolerance to therapy.
6. For del(5q) patients, failed prior treatment with at least 2 cycles started of lenalidomide defined as no response to treatment, loss of response at any time point, or progressive disease/intolerance to therapy.
7. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
8. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence; tubal ligation, partner's vasectomy) prior to Cycle 1 Day 1 (C1D1) and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

1. Patient has a known history of HIV infection (testing not mandatory).

2. Patient has any of the following cardiac abnormalities:

   • symptomatic congestive heart failure
   • myocardial infarction ≤ 6 months prior to enrollment
   • unstable angina pectoris as designated by the treating physician
   • serious uncontrolled cardiac arrhythmia as designated by the treating physician
   • QTcF (Fridericia's correction formula) ≥ 450 msec
3. Concomitant malignancies or previous malignancies with less than a 1-year disease free interval at the time of enrollment. Patients with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (i.e. cervix) may enroll irrespective of the time of diagnosis.
4. Use of chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 14 days of the first day of study drug treatment.
5. No concurrent use of erythroid stimulating agents, Granulocyte-colony stimulating factor (G-CSF), Granulocyte-macrophage colony-stimulating factor (GM-CSF) is allowed during study except in cases of febrile neutropenia where G-CSF can be used for short term. Growth factors must be stopped two weeks prior to study.
6. Pregnant women are excluded from this study because LB-100 has not been studied in pregnant subjects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with LB-100, breastfeeding should be discontinued if the mother is treated with LB-100.

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: LB-100 for Intravenous administration; Phase Ib: Escalating doses of LB-100 administered. Phase 2: Safe dose of LB-100 from phase Ib administered.	Drug: LB-100; Phase Ib: Two escalating doses of LB-100 in two separate cohorts will be administered intravenously on days 1, 3 and 5 of a 21-day cycle over 120 minutes. Phase 2: Safe dose of LB-100 as determined from phase Ib will be administered intravenously on days 1, 3 and 5 of a 21-day cycle over 120 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
For Phase Ib - Number of patients with adverse events related to the study treatment as a measure of safety and tolerability of LB-100 study drug	Number of patients with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0)	From the first dose of the study drug to 30-days following last dose of the study drug
For Phase 2 - Best overall response rate of patients to the study treatment as a measure of efficacy of LB-100 study drug	Best overall response rate of the patients to the study treatment as assessed by International Working Group (IWG) 2006 criteria	At screening and then at the end of Cycle 3 and Cycle 6. (Each cycle is 21 days)

Collaborators and Investigators

• Sponsor: Lixte Biotechnology Holdings, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2019
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: March 18, 2019
• First Submitted That Met QC Criteria: March 20, 2019
• First Posted (Actual): March 22, 2019

Study Record Updates

• Last Update Posted (Actual): April 8, 2019
• Last Update Submitted That Met QC Criteria: April 4, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; LB100
• Other Study ID Numbers: MCC-19635

Drug and device information, study documents

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