Study Stopped
Study was discontinued due to lack of recruitment.
Early Phase Evaluation of ABC294640 in Patients With Refractory/Relapsed Diffuse Large B-cell Lymphoma or Kaposi Sarcoma
ABC-102
An Early-Phase Clinical Trial Evaluating ABC294640 in Patients With Refractory/Relapsed Diffuse Large B-cell Lymphoma or Kaposi Sarcoma
1 other identifier
interventional
N/A
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Jul 2014
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2014
CompletedFirst Submitted
Initial submission to the registry
August 28, 2014
CompletedFirst Posted
Study publicly available on registry
September 3, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2019
CompletedDecember 7, 2017
December 1, 2017
4.9 years
August 28, 2014
December 5, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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 Outcomes (4)
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
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
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
Study Arms (1)
ABC294640
EXPERIMENTALPatients will receive ABC294640 orally in gelatin capsules BID.
Interventions
Eligibility Criteria
You may not qualify if:
- For patients with DLBCL, the patient is not a candidate for hematopoietic stem cell transplantation (as determined by medical oncologists at participating institutions) or has failed stem cell transplantation.
- Tumor progression after receiving standard/approved chemotherapy, or lack of candidacy for standard therapy.
- One or more tumors measurable on PET-CT scan (DLBCL), CT scan (KS), or by clinical exam of skin (KS).
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3.
- Life expectancy of at least 3 months.
- Age ≥ 18 years.
- Signed, written IRB-approved informed consent.
- A negative pregnancy test (if female).
- Acceptable liver function:
- Bilirubin ≤ 3 times upper limit of normal (CTCAE Grade 2 baseline)
- AST (SGOT), ALT (SGPT) ≤ 3 x ULN (CTCAE Grade 1 baseline)
- Serum creatinine ≤ 1.5 X ULN (CTCAE Grade 1 baseline)
- Acceptable hematologic status:
- Absolute neutrophil count ≥ 1000 cells/mm3
- Platelet count ≥ 75,000 (plt/mm3) (CTCAE Grade 1 baseline)
- +20 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Louisiana State University Health Sciences Center
New Orleans, Louisiana, 70112, United States
Related Publications (3)
Qin Z, Dai L, Trillo-Tinoco J, Senkal C, Wang W, Reske T, Bonstaff K, Del Valle L, Rodriguez P, Flemington E, Voelkel-Johnson C, Smith CD, Ogretmen B, Parsons C. Targeting sphingosine kinase induces apoptosis and tumor regression for KSHV-associated primary effusion lymphoma. Mol Cancer Ther. 2014 Jan;13(1):154-64. doi: 10.1158/1535-7163.MCT-13-0466. Epub 2013 Oct 18.
PMID: 24140934BACKGROUNDDai L, Plaisance-Bonstaff K, Voelkel-Johnson C, Smith CD, Ogretmen B, Qin Z, Parsons C. Sphingosine kinase-2 maintains viral latency and survival for KSHV-infected endothelial cells. PLoS One. 2014 Jul 10;9(7):e102314. doi: 10.1371/journal.pone.0102314. eCollection 2014.
PMID: 25010828BACKGROUNDDai L, Trillo-Tinoco J, Bai A, Chen Y, Bielawski J, Del Valle L, Smith CD, Ochoa AC, Qin Z, Parsons C. Ceramides promote apoptosis for virus-infected lymphoma cells through induction of ceramide synthases and viral lytic gene expression. Oncotarget. 2015 Sep 15;6(27):24246-60. doi: 10.18632/oncotarget.4759.
PMID: 26327294BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Suki Subbiah, MD
Louisiana State University Health Sciences Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 28, 2014
First Posted
September 3, 2014
Study Start
July 1, 2014
Primary Completion
June 1, 2019
Study Completion
December 1, 2019
Last Updated
December 7, 2017
Record last verified: 2017-12