Safety and Dose Study of GRN163L and Velcade to Treat Patients With Refractory or Relapsed Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to determine safety and the maximum tolerated dose (MTD) of GRN163L and Velcade with and without Decadron when administered to patients with refractory or relapsed multiple myeloma.

Detailed Description
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GRN163L is a telomerase template antagonist with in vitro and in vivo activity in a variety of tumor model systems. Telomerase is an enzyme that is active primarily in tumor cells and is crucial for the indefinite growth of tumor cells. Inhibition of telomerase may result in antineoplastic effects.

Official Title
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A Phase I Study of GRN163L in Combination With Bortezomib and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Imetelstat Sodium (GRN163L)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of multiple myeloma (either secretory or nonsecretory disease) Relapsed or refractory disease ECOG performance status 0-2 Adequate hepatic/renal function and platelet count If previously treated with an anthracycline, anthracenedione, or trastuzumab, must have left ventricular ejection fraction > 50% Fully recovered from any previous cancer treatments and/or major surgery Exclusion Criteria: Prior allogeneic bone marrow transplant, including syngeneic transplant Bone marrow transplant within 12 weeks prior to study Known intracranial disease or epidural disease Inability to tolerate Velcade Inability to tolerate Decadron Prior malignancy (within the last 3 years) Clinically significant cardiovascular disease or condition Active or chronically recurrent bleeding (eg, active peptic ulcer disease Prolongation of PT or aPTT > the ULN or fibrinogen < the LLN Clinically relevant active infection Serious co-morbid medical conditions, including cirrhosis and chronic obstructive or chronic restrictive pulmonary disease Any other cancer therapy within 4 weeks prior to study, with nitrosourea within 6 weeks prior to study Investigational therapy within 4 weeks prior to study Anti-platelet therapy within 2 weeks prior to study, other than low dose aspirin prophylaxis therapy and low dose heparin administration for management of IV access devices Radiation therapy within 4 weeks prior to study Major surgery within 4 weeks prior to study Active autoimmune disease requiring immunosuppressive therapy Known positive serology for HIV

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

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>3+3 cohort dose escalation | Drug: Imetelstat Sodium (GRN163L)<br>* 25% dose escalation infused over 2 hours weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  | First 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, PK and efficacy |  | Baseline to 28 days after last dose of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myeloma, Multiple Myeloma, Relapsed Multiple Myeloma, Refractory Multiple Myeloma, Relapsed or Refractory Multiple Myeloma