Study of XL999 in Patients With Multiple Myeloma

Study Overview
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Brief Summary
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This clinical study is being conducted at multiple sites to determine the activity, safety, and tolerability of XL999 when given weekly to patients with relapsed or refractory multiple myeloma. XL999 is a small molecule inhibitor of cellular factors including VEGFR, PDGFR, and FGFR that may be involved in multiple myeloma.

Official Title
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A Phase 2 Study of XL999 in Subjects With Relapsed/Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: XL999


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females with a diagnosis of MM based on bone marrow aspirate and biopsy with ≥10% plasma cells (or biopsy of a tissue with monoclonal plasma cells), M protein level in the serum or urine, and evidence of end organ or tissue impairment (hypercalcemia, renal insufficiency, anemia, or lytic bone lesions), as defined by The International Myeloma Working Group Criteria (2003), at initial diagnosis (before initiation of chemotherapy) Measurable disease defined as serum and/or urine M component by electrophoresis Refractory to or relapsed after 2 prior treatment regimens (chemotherapy, biologic or hematopoietic stem cell transplantation) Concurrent therapy with a bisphosphonate is acceptable ECOG performance status of 0 or 1 Life expectancy ≥3 months Adequate liver function No other malignancies within 5 years Signed informed consent Exclusion Criteria: Nonsecretory myeloma, monoclonal gammopathy of uncertain significance (MGUS), or smoldering myeloma Anticancer therapy including chemotherapeutic, biologic, or investigational agents, including dexamethasone, within 30 days of XL999 treatment Hematopoietic stem cell transplantation within the previous 6 weeks Radiation to ≥33% of bone marrow within 30 days of XL999 treatment Subject has not recovered to grade ≤1 or to within 10% of baseline from adverse events due to investigational or chemotherapeutic drugs that were administered >30 prior to study enrollment Uncontrolled and/or intercurrent illness Pregnant or breastfeeding females Known 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

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: XL999|Treatment consisted of 8 weekly infusions of 2.4 mg/kg of XL999 with each infusion given over 4 hours, unless drug-related toxicity required a dosing delay or adjustment. In the absence of progressive disease and unacceptable toxicity, subjects may have received XL999 treatment weekly for up to 1 year on this study.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | Inclusion of subject until disease progression | 
| Safety and tolerability |  | Inclusion until 30 days post last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response |  | Inclusion until disease progression | 
| Progression-free survival |  | Inclusion until disease progression | 
| Overall survival |  | Inclusion until 180-day Follow-up or death |