Clinical trial NCT02229981 (phase 1/phase 2, status: withdrawn)
Conditions: diffuse large b cell lymphoma, kaposi sarcoma
ICD codes: S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, C46.9, C46.0, C46.2, C46.1, C46.3, C46.4, C46.50
Drugs: abc294640
SMILES: ClC1=CC=C(C=C1)C12CC3CC(CC(C3)(C1)C(=O)NCC1=CC=NC=C1)C2
Reason stopped: 
    study was discontinued due to lack of recruitment.
  
Eligibility criteria:

        Inclusion Criteria

          1. 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.

          2. 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.

          3. Tumor progression after receiving standard/approved chemotherapy, or lack of candidacy
             for standard therapy.

          4. One or more tumors measurable on PET-CT scan (DLBCL), CT scan (KS), or by clinical
             exam of skin (KS).

          5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3.

          6. Life expectancy of at least 3 months.

          7. Age ≥ 18 years.

          8. Signed, written IRB-approved informed consent.

          9. A negative pregnancy test (if female).

         10. 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)

         11. Acceptable hematologic status:

               -  Absolute neutrophil count ≥ 1000 cells/mm3

               -  Platelet count ≥ 75,000 (plt/mm3) (CTCAE Grade 1 baseline)

               -  Hemoglobin ≥ 8 g/dL

         12. Urinalysis: No clinically significant abnormalities.

         13. PT and PTT ≤ 1.5 X ULN after correction of nutritional deficiencies that may
             contribute to prolonged PT/PTT.

         14. 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).

        Exclusion Criteria

          1. 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.

          2. 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.

          3. Patients with active, life-threatening bacterial or fungal infections.

          4. Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy
             within one month prior to study entry.

          5. Unwillingness or inability to comply with procedures required in this protocol.

          6. 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.

          7. Patients who are currently receiving any other investigational agent.

          8. 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.

          9. Patients who are currently taking Coumadin or Coumadin derivatives.

         10. 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.

         11. Patients who are currently participating in any other clinical trial of an
             investigational product.

         12. Allergy to radiographic contrast