Early Phase Evaluation of ABC294640 in Patients With Refractory/Relapsed Diffuse Large B-cell Lymphoma or Kaposi Sarcoma
- Registration Number
- NCT02229981
- Lead Sponsor
- RedHill Biopharma Limited
- Brief Summary
This is a sequential Phase I and IIa study to identify the maximum tolerated dose and to evaluate safety, tolerability, toxicity, pharmacokinetics and pharmacodynamics of the oral sphingosine kinase inhibitor ABC294640 specifically in patients with diffuse large B-cell lymphoma (DLBCL), including virus-associated (e.g., KSHV- or EBV-associated) DLBCL or Kaposi Sarcoma (KS) after failure of or intolerance to initial standard therapy.
- Detailed Description
Sphingosine Kinase (SK) is an innovative target for anti-cancer therapy due to its critical role in lipid metabolism which drives cancer cell growth. We have found that the SK inhibitor ABC294640 (which is formulated for clinical use as an oral agent) significantly inhibits and reverses progression of virus-associated DLBCL in pre-clinical animal models \[Qin et a., 2014\]. In addition, we have found that ABC294640 selectively induces death for virus-infected endothelial cells in a laboratory model relevant to KS, with selective sparing of uninfected cells \[Dai et al., 2014; Dai et al., 2015\]. Both DLBCL and KS disproportionately impact patients with immune-deficiencies, including HIV infection, for whom standard chemotherapeutic approaches are less effective and incur greater side effects. Therefore, this trial which utilizes a well-tolerated, oral agent to inhibit SK for DLBCL and KS patients may provide a unique approach to treatment.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ABC294640 ABC294640 Patients will receive ABC294640 orally in gelatin capsules BID.
- Primary Outcome Measures
Name Time Method Determine Maximum tolerated dose (MTD) of ABC294640 in patients with refractory/relapsed DLBCL or KS and determine tolerability at MTD. Patients will be followed until a dose limiting toxicity (DLT) is experienced, if present, expected within the first 8 weeks Evaluate safety of ABC294640 in patients with refractory/relapsed DLBCL or KS If present, expected within 8 weeks
- Secondary Outcome Measures
Name Time Method Measure plasma levels of ABC294640 (pharmacokinetics) in patients with DLBCL or KS Days 1 and 28, 1,2, 4, 8 and 24 hours post drug administration Evaluate antitumor activity of ABC294640 in virus-associated DLBCL or KS patients by objective radiographic assessment using PET (DLBCL) or CT (KS) criteria, or measurement of clinically evident skin lesions (KS) Within 14 Days of Treatment Day 1 and then on Day 28 of Cycles 2, 4, 6, 8, etc., stopping if tumor progression is observed Measure plasma levels of sphingosine-1-phosphate in response to ABC294640 in patients with DLBCL or KS Days 1,8,15 and 28 in Cycle 1, Days 14 and 28 for all subsequent cycles and at the end of treatment study Measure levels of circulating CD4+ T cell count, KSHV/EBV viral loads, and HIV viral load (if applicable) in response to ABC294640 in patients with DLBCL or KS Days 1, 8, 15 and 22 for cycles 1-3 and Days 1, 8, 15, 22 and 28 for Cycle 4
Trial Locations
- Locations (1)
Louisiana State University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States