AzTrials
AzTrials

Diffuse Large B Cell LymphomaPhase 1/2ABC-102NCT02229981

Early Phase Evaluation of ABC294640 in Patients With Refractory/Relapsed Diffuse Large B-cell Lymphoma or Kaposi Sarcoma

A Phase 1/2 study testing ABC294640 in people with Diffuse Large B Cell Lymphoma and Kaposi Sarcoma, run by RedHill Biopharma Limited at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diffuse Large B Cell Lymphoma, Kaposi Sarcoma
What is being tested?
ABC294640
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Jul 2014to Dec 2019
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Pathologically confirmed DLBCL or KS. In the case of patients with DLBCL, the disease must be radiographically refractory to standard therapy, or relapsed following standard therapy (one or more tumors measurable on PET-CT scan). In the case of patients with KS, the disease must be either radiographically or clinically refractory (persistent skin lesions) to standard therapy or relapsed following standard therapy (one or more tumors measurable on CT scan or through direct measurement of skin tumors). Please see caveats for antineoplastic therapies in Exclusion criteria below.
  • 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.
Show all 24Show fewer
  • 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)
  • Hemoglobin ≥ 8 g/dL
  • Urinalysis: No clinically significant abnormalities.
  • PT and PTT ≤ 1.5 X ULN after correction of nutritional deficiencies that may contribute to prolonged PT/PTT.
  • For men and women of child-producing potential, willingness to use of effective contraceptive methods during the study. If female (or female partner of male subject), is either not of childbearing potential (defined as postmenopausal for ≥ 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy or hysterectomy]) or practicing one of the following medically acceptable methods of birth control and agrees to continue with the regimen throughout the duration of the study:
  • Oral, implantable or injectable contraceptives for 3 consecutive months before the Baseline/Randomization Visit.
  • Total abstinence from sexual intercourse (≥ 1 complete menstrual cycle before the Baseline/Randomization Visit).
  • Intrauterine device (IUD).
  • Double barrier method (condoms, sponge, diaphragm or vaginal ring with spermicidal jellies or cream).

Who cannot join

  • New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.
  • Pregnant or nursing women. NOTE: Women of child-bearing potential and men must agree to use barrier methods (preferably condoms) or other methods of birth control at your doctor's discretion, or abstain from sexual activity, prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Patients with active, life-threatening bacterial or fungal infections.
  • Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within one month prior to study entry.
  • Unwillingness or inability to comply with procedures required in this protocol.
  • Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
Show all 12Show fewer
  • Patients who are currently receiving any other investigational agent.
  • Patients who are receiving drugs other than highly active antiretroviral therapy (HAART) or trimethoprim-sulfamethoxazole that are sensitive substrates of CYP450 1A2, 3A4, 2C9, 2D6, or 2C19, or strong inhibitors or inducers of these isozymes that cannot be stopped at least 7 days or 5 half-lives (whichever is longer) before starting treatment with ABC294640 and either replaced with another appropriate medication or not given for the duration of the clinical study. Patients on HAART will be restricted to preferred, potent agents with no demonstrated interactions with CYP450 isoforms for which significant interactions are predicted with ABC294640 (1A2, 2C9, or 2C19 for which ABC294640 IC50 < 1uM). These include tenofovir, FTC, 3TC, abacavir, darunavir, atazanavir, norvir, raltegravir, dolutegravir, elvitegravir, cobicistat, and maraviroc. Switching of ART prior to study entry is permitted given significant data for improvement/maintenance of HIV suppression when switching regimens in other contexts.
  • Patients who are currently taking Coumadin or Coumadin derivatives.
  • Patients who have received any antineoplastic therapy within 1 month of starting treatment with ABC294640 or who have not adequately recovered from side effects and toxicities of previous antineoplastic therapy.
  • Patients who are currently participating in any other clinical trial of an investigational product.
  • Allergy to radiographic contrast

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Louisiana State University Health Sciences Center

    New Orleans, Louisiana, 70112

Other trials in United States

About this study

Official title: An Early-Phase Clinical Trial Evaluating ABC294640 in Patients With Refractory/Relapsed Diffuse Large B-cell Lymphoma or Kaposi Sarcoma

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.

Read the 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.

Being tested
ABC294640
Keywords
Lymphoma, B-cell Lymphomas, Diffuse Large B-cell Lymphoma, Lymphosarcoma, Kaposi's Sarcoma-associated Herpesvirus, KHSV, Human Immunodeficiency Virus, HIV, Epstein-Barr Virus, EBV, Kaposi sarcoma
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Sarcoma, Kaposi, Lymphoma, Lymphoma, B-Cell, Lymphoma, Non-Hodgkin, Acquired Immunodeficiency Syndrome, Epstein-Barr Virus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ABC294640Drug

    Also called Yeliva

Study groups in NCT02229981
Study groupRoleWhat they receive
ABC294640ExperimentalPatients will receive ABC294640 orally in gelatin capsules BID.
Receives: Drug: ABC294640

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determine Maximum tolerated dose (MTD) of ABC294640 in patients with refractory/relapsed DLBCL or KS and determine tolerability at MTD.

    Measured: Patients will be followed until a dose limiting toxicity (DLT) is experienced, if present, expected within the first 8 weeks

  2. Evaluate safety of ABC294640 in patients with refractory/relapsed DLBCL or KS

    Measured: If present, expected within 8 weeks

Secondary outcomes (4)

  1. Measure plasma levels of ABC294640 (pharmacokinetics) in patients with DLBCL or KS

    Measured: Days 1 and 28, 1,2, 4, 8 and 24 hours post drug administration

  2. Measure plasma levels of sphingosine-1-phosphate in response to ABC294640 in patients with DLBCL or KS

    Measured: Days 1,8,15 and 28 in Cycle 1, Days 14 and 28 for all subsequent cycles and at the end of treatment study

  3. 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

    Measured: Days 1, 8, 15 and 22 for cycles 1-3 and Days 1, 8, 15, 22 and 28 for Cycle 4

  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)

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Sep 2014 (estimated)
  2. Study startJul 2014
  3. Primary completionJun 2019 (estimated)
  4. Study completionDec 2019 (estimated)

Why it stopped: Study was discontinued due to lack of recruitment.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02229981
Sponsor's protocol ID
ABC-102
Acronym
ABC-102
Status last verified
Dec 2017
First submitted
28 Aug 2014
Last updated
7 Dec 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 24140934

  • Dai 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.

    PubMed 25010828

  • Dai 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.

    PubMed 26327294

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ABC294640 in people with Diffuse Large B Cell Lymphoma and Kaposi Sarcoma, run by RedHill Biopharma Limited at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 7 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine Maximum tolerated dose (MTD) of ABC294640 in patients with refractory/relapsed DLBCL or KS and determine tolerability at MTD. (time frame: Patients will be followed until a dose limiting toxicity (DLT) is experienced, if present, expected within the first 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02229981, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in