Dose-Escalation Study of Pixantrone Monotherapy in Pediatric Patients With Relapsed or Refractory Cancer

NCT02800889 | Withdrawn Phase 1 DMC

• 1 other identifier: PIX111
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, open-label, dose escalation study to evaluate the safety, pharmacokinetics, and antitumor activity of pixantrone in pediatric patients with relapsed or refractory solid tumors (excluding those with CNS tumors) or lymphoma.

Conditions

Lymphoma; Solid Tumor (Excluding CNS)

Keywords

relapsed; refractory; solid tumors

Outcome Measures

Primary Outcomes (2)

• MTD, defined as the highest dose level at which no more than 1/6 patients experience DLT

  Dose Escalation- The study will follow a standard 3+3 patient cohort escalation design, evaluating up to 4 dose levels.

  28 days

• Anti-tumor activity of pixantrone at the MTD

  Dose Expansion Cohort- Anti-tumor activity will be summarized by disease type, dose level, and age cohort for all patients in the evaluable population. The best overall response rate, defined as the proportion of patients that achieved a complete or partial response, will be summarized by disease type and a 95% confidence interval will be provided. A similar summary will be provided for the complete response rate.

  approx. 1 year

Study Arms (1)

Treatment: Pixantrone

EXPERIMENTAL

Each patient will receive pixantrone monotherapy administered intravenously once on days 1, 8, and 15 up to six 28-day cycles of pixantrone monotherapy, with two additional cycles in patients who continue to benefit from treatment. At least 6 patients each from Age Cohorts 1 and 2 will be accrued into dose escalation cohorts. The study will be opened to patients of Age Cohort 3 only after at least 6 patients in Age Cohorts 1 and 2 (combined) have been evaluated for toxicity. During the dose escalation phase, participants who are inevaluable for DLT for reasons unequivocally unrelated to toxicity will be replaced. Expansion cohort accrual quota-At least 15 evaluable patients treated with the MTD/optimal dose will be accrued in total, of which 7 patients will be in Age Cohort 2.

Drug: Pixantrone

Interventions

Pixantrone DRUG

Pixantrone

Also known as: Pixantrone (BBR 2778)

Treatment: Pixantrone

Eligibility Criteria

• Age: 6 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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)
• 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
• 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
• In dose-escalation accrual, patients may have un-measurable disease (such as bone marrow/bone involvement or diffuse tumors)
• 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
• 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 \[Appendix 18.5\])
• Karnofsky-Lansky performance status (as per age of patient) ≥50 (Appendix 18.1)
• 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%
• Hemoglobin ≥8 g/dL (can be post-transfusion)

You may not qualify if:

• Investigator-predicted life expectancy of less than two months
• Investigator-predicted inability to tolerate pixantrone monotherapy treatment adverse effects for less than two months
• Prior anthracycline treatment with a cumulative dose exceeding 450 mg/m2 (calculated based on doxorubicin equivalents)
• 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
• Major surgery ≤7 days and/or with incomplete/inadequate wound healing prior to start of study treatment
• Known acute or chronic hepatitis B or hepatitis C virus infection
• Known seropositivity for human immunodeficiency virus (HIV)
• Any experimental/investigational therapy ≤28 days prior to start of study treatment
• Myocardial infarction within the past 6 months
• New York Heart Association class II, III or IV heart failure
• Any contraindication, known allergy, or hypersensitivity to any investigational drug(s)
• Pregnant or lactating
• Planned radiotherapy or surgical procedures for the qualifying malignancy
• Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study procedures or follow-up schedules
• 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

Sponsors & Collaborators

• CTI BioPharma: lead

Study Sites (1)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

MeSH Terms

Conditions

Lymphoma; Recurrence

Interventions

pixantrone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Leo Mascarenhas, MD. MS.

  CHLA

  PRINCIPAL INVESTIGATOR

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: June 3, 2016
• First Posted: June 15, 2016
• Study Start: October 24, 2016
• Primary Completion: July 10, 2018
• Study Completion: July 10, 2018
• Last Updated: January 29, 2020

Record last verified: 2020-01

Locations

US (1)