Clinical trial NCT02800889 (phase 1, status: withdrawn)
Conditions: lymphoma, solid tumor (excluding cns)
ICD codes: S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S
Drugs: pixantrone
SMILES: NCCNC1=CC=C(NCCN)C2=C1C(=O)C1=C(C=NC=C1)C2=O
Reason stopped: 
    study withdrawn; no participants enrolled
  
Eligibility criteria:

        Inclusion Criteria:

          1. Patient and/or guardian have signed an Informed Consent Form and Assent approved by
             the Institutional Review Board or Institutional Ethics Committee, as appropriate and
             necessary, on a per-age basis

          2. Age 6 months to 21 years old (initial qualifying diagnosis must have been made at or
             before the age of 18 and the patient must be under the care of a pediatric
             hematologist/oncologist)

          3. Patient received a diagnosis of lymphoma or any non-hematologic malignancy (except
             central nervous system [CNS] tumors) for which the patient is considered relapsed or
             refractory. (NOTE: CNS metastases are allowable in patients who are deemed not at risk
             for progression during the first 30 days, who are neurologically stable, and, if on
             corticosteroids, have been on a stable corticosteroid dose for at least 2 weeks.)
             Patients who have >1 malignancy ongoing during screening are not eligible

          4. Patient must have one or more of the following treatment statuses:

               -  Has failed at least 2 prior lines of chemotherapy

               -  Has no curative chemotherapy treatment option available

               -  Is not considered a candidate for available chemotherapy treatment options

          5. In dose-escalation accrual, patients may have un-measurable disease (such as bone
             marrow/bone involvement or diffuse tumors)

          6. In dose-escalation accrual, patients may have un-measurable disease in cases where the
             standard of care would indicate the need for adjuvant chemotherapy after definitive
             surgery or radiation, but for whom no standard chemotherapy options are available

          7. In expansion cohort accrual, patients must have disease that is evaluable or
             measurable for response and progression per standard criteria for their diagnosis
             (Refer to the Appendices: RECIST 1.1 Criteria for Evaluation of Solid Tumors,
             Including Neuroblastoma, Appendix 18.4], Evaluation of Neuroblastoma [Appendix 18.6],
             and the Lymphoma Staging and Disease Response Criteria [Appendix 18.5])

          8. Karnofsky-Lansky performance status (as per age of patient) ≥50 (Appendix 18.1)

          9. Patient must have one or more of the following cardiac function measurements by
             echocardiogram:

               -  Left ventricular ejection fraction (LVEF) ≥55%

               -  Left ventricular shortening fraction (LVSF) ≥27%

         10. Hemoglobin ≥8 g/dL (can be post-transfusion)

         11. Platelet count ≥75 × 109/L

         12. Absolute neutrophil count (ANC) ≥0.75 × 109/L

         13. Serum direct/conjugated bilirubin ≤1.5 × upper limit of normal (ULN); patients with
             clinically diagnosed Gilbert's syndrome and total bilirubin ≤5 × ULN may be enrolled

         14. Aspartate aminotransferase (AST; also called serum glutamic-oxaloacetic transaminase
             [SGOT]) and alanine aminotransferase (ALT; also called serum glutamic-pyruvic
             transaminase [SGPT]) ≤2.5 × ULN, or ≤5 × ULN if elevation is due to hepatic
             involvement by tumor

         15. Serum creatinine ≤2 × ULN

         16. Patients must meet the following criteria with respect to prior cancer therapy,
             radiotherapy, and stem cell transplants:

               1. Myelosuppressive chemotherapy: At least 3 weeks must have elapsed since the
                  completion of myelosuppressive chemotherapy (4 weeks if prior nitrosourea) and
                  resolution of all nonhematologic toxicities to ≤grade 1.

               2. Biologic (anti-neoplastic agent):

                    -  Oral tyrosine kinase inhibitors or other similar agents. At least 7 days
                       must have elapsed since the completion of therapy with a biologic agent and
                       all non-hematologic toxicities must have resolved to ≤grade 1 prior to
                       enrollment

                    -  Anti-IGFR-1R and other monoclonal antibodies: the shorter of 3 half-lives or
                       6 weeks must have elapsed since previous monoclonal antibody therapy and
                       resolution of all non-hematologic toxicities to ≤grade 1 prior to enrollment

               3. Myeloid Growth Factor: Must not have received within 1 week prior to entry into
                  this study (2 weeks in the case of PEG-filgrastim)

               4. Radiotherapy: At least 4 weeks must have elapsed and all non-hematologic
                  toxicities must have resolved to ≤grade 1 prior to enrollment. Previously
                  radiated lesions cannot be used to assess response unless those sites are the
                  sites of disease progression

               5. Stem cell transplant (SCT): For autologous SCT, ≥3 months must have elapsed. For
                  allogeneic SCT, ≥6 months must have elapsed and there must be no evidence of
                  active graft versus host disease

         17. All acute toxicities related to prior treatment recovered to grade ≤1 , except
             alopecia and hematologic parameters specified in the inclusion criteria

         18. Willingness and ability to comply with the visit schedule and assessments required by
             the study protocol, including effective birth control (Section 5.4) for sexually
             active patients

        Exclusion Criteria:

          1. Investigator-predicted life expectancy of less than two months

          2. Investigator-predicted inability to tolerate pixantrone monotherapy treatment adverse
             effects for less than two months

          3. Prior anthracycline treatment with a cumulative dose exceeding 450 mg/m2 (calculated
             based on doxorubicin equivalents)

          4. Active National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
             (CTCAE) ≥grade 3 infection, or a lower grade infection deemed resistant or refractory
             to available antimicrobial agents, or infection requiring ongoing antibiotic treatment

          5. Major surgery ≤7 days and/or with incomplete/inadequate wound healing prior to start
             of study treatment

          6. Known acute or chronic hepatitis B or hepatitis C virus infection

          7. Known seropositivity for human immunodeficiency virus (HIV)

          8. Any experimental/investigational therapy ≤28 days prior to start of study treatment

          9. Myocardial infarction within the past 6 months

         10. New York Heart Association class II, III or IV heart failure

         11. Any contraindication, known allergy, or hypersensitivity to any investigational
             drug(s)

         12. Pregnant or lactating

         13. Planned radiotherapy or surgical procedures for the qualifying malignancy

         14. Any psychological, familial, sociological, or geographical condition potentially
             hampering compliance with the study procedures or follow-up schedules

         15. Other severe and/or uncontrolled medical disease that could compromise participation
             in the study, or any medical or psychiatric condition that, in the opinion of the
             investigator, would make study drug administration hazardous or obscure the
             interpretation of data