Safety and Tolerability of RGB-286638 in Patients With Selected, Relapsed or Refractory Hematological Malignancies

Study Overview
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Brief Summary
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The purpose of the study is to determine the safety and tolerability of RGB-286638, a novel, multi-targeted kinase inhibitor, administered to patients with selected, relapsed or refractory hematological malignancies.

Official Title
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Phase 1 Open-label, Dose-escalation Clinical Study of the Safety and Tolerability of RGB-286638, a Novel, Multi-targeted Kinase Inhibitor, Administered to Patients With Selected, Relapsed or Refractory Hematological Malignancies

Conditions
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Hematological Malignancies

Intervention / Treatment
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* Drug: RGB-286638


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically/cytologically confirmed diagnosis of: Multiple myeloma (MM) Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL) Mantle Cell Lymphoma (MCL) Chronic Myelogenous Leukemia (CML) Refractory to/relapsed after and/or intolerant of one or more standard therapies or for which no standard therapy exists. ECOG performance status 0-2. Adequate bone marrow, cardiovascular, renal and hepatic function Recovery from all adverse events due to prior therapies Contraception Exclusion Criteria: Prior chemotherapy, monoclonal antibodies, investigational agents, or radiation therapy (involving ≥ 30% of the active bone marrow) within 14 days prior to the first dose (note nitrosoureas and mitomycin are not permitted for at least 42 days before the first dose of RGB-286638). CNS involvement of the hematological malignancy. Active or unstable cardiac disease and/or history of myocardial infarction within 6 months and/or history of clinically significant ventricular arrhythmias. Concomitant therapies that are known to prolong the QT interval and are associated with a risk of Torsades de Pointes (TdP) are not permitted within 7 days before the first dose; however, amiodarone is not permitted within 90 days before the first dose. Patients with uncontrolled and unstable intercurrent illness. Concomitant therapy with inhibitors and/or inducers of CYP450 3A4 within 1 week of the first dose. Bleeding disorder unrelated to hematological malignant disease. HIV or HIV-related malignancy. History of other malignancies except: (i) adequately treated basal or squamous cell carcinoma of the skin; (ii) curatively treated, a) in situ carcinoma of the uterine cervix, b) prostate cancer, or c) superficial bladder cancer; or (iii) other curatively treated solid tumor with no evidence of disease for ≥ 2 years. Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: RGB-286638|The starting dose is a flat-fixed dose of 40 mg given i.v. over 60 min, weekly x3, of a 28-days cycle (q4 weeks)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose |  | 28 Days of Cycle 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of escalating doses of RGB-286638 | Frequency and Severity of Adverse Events based on NCI Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 (2003) | 30 days after the last study drug is given to a subject | 
| Objective Tumor Response |  | At the Time of Final Analysis | 
| Pharmacokinetic Properties |  | At the end of Cycle 1 (28 days) | 
| Pharmacodynamic properties |  | At the end of Cycle 1 (28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RGB-286638, Hematological Malignancies