Clinical trial · Interventional
Combination Chemotherapy Plus PSC-833 in Treating Children With Refractory or Relapsed Acute Leukemia
A PHASE I COOPERATIVE AGREEMENT PEDIATRIC TRIAL OF MITOXANTRONE, ETOPOSIDE AND PSC-833 (PSC-ME) THERAPY IN PATIENTS WITH RELAPSED AND REFRACTORY ACUTE LEUKEMIA
NCT00002912CI-TRIAL-00009246completedPhase 1ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
Phase I trial to study the effectiveness of PSC-833 plus etoposide and mitoxantrone in treating children who have refractory or relapsed acute leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Some cancers become resistant to chemotherapy drugs. Combining PSC-833 with chemotherapy may reduce resistance to the drug and allow more cancer cells to be killed.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Leukemia | Leukemia | ONTOLOGY_EXACT | 0.90 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| etoposide | Drug | Etoposide | ALIAS |
| mitoxantrone hydrochloride | Drug | Mitoxantrone | ALIAS |
| valspodar | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Arm I
- description
- Patients undergo induction therapy consisting of etoposide IV and mitoxantrone IV on days 1-5. Patients then receive PSC-833 IV over 124 hours beginning on day 2. A second course is administered no sooner than 21 days from the start of the first course if the marrow is hypocellular after the first course. Patients with persistent disease after 2 induction courses are removed from the study. Patients receive a total of 3 courses of etoposide/mitoxantrone. Patients who achieve complete remission after 1 induction course receive 2 courses of etoposide/mitoxantrone with PSC-833 as consolidation, beginning within 4 weeks of attainment of complete remission. Patients who achieve complete remission after 2 induction courses receive 1 course of etoposide/mitoxantrone with PSC-833 as consolidation. Cohorts of 3-6 patients receive escalating doses of PSC-833 until the maximum tolerated dose is determined. Patients are followed every 6 months.
- interventionNames
- Drug: etoposide
- Drug: mitoxantrone hydrochloride
- Drug: valspodar
Primary outcomes (0)
[]Eligibility
Eligibility (as posted)
- Sex
- All
- Maximum age
- 21 Years
Show eligibility criteria text
DISEASE CHARACTERISTICS: * Acute myeloid leukemia (AML) in one of the following categories: * First relapse if initial CR less than 6 months * Refractory to first or second induction with daunomycin, cytarabine, and thioguanine (DAT) or other anthracycline-containing regimens * Relapse following bone marrow transplantation provided good trilineage engraftment followed transplant and greater than 6 months since transplant * Presentation with secondary AML or AML evolving from myelodysplastic syndrome --Acute lymphocytic leukemia in one of the following categories: * In second or subsequent relapse or failed second or later induction attempts regardless of prior remissions * Relapsed following bone marrow transplantation provided good trilineage engraftment followed transplant and greater than 6 months since transplant * No isolated CNS or extramedullary relapse PATIENT CHARACTERISTICS: * Age: Under 22 at diagnosis * Performance status: Karnofsky 50-100% (ECOG 0-2) * Lansky 40-100% (in patients under 12 years of age) * Life expectancy: At least 8 weeks * Bilirubin less than 1.5 mg/dL * ALT less than twice normal * Creatinine normal for age (within 2 standard deviations) OR glomular filtration rate at least 70 mL/min * Albumin at least 3 g/dL * Ejection fraction greater than 50% at rest or with 5% increase with exercise OR shortening fraction greater than 27% by echocardiogram * No history of clinical heart failure * No uncontrolled infection * No anticonvulsant therapy * No history of allergic reactions or anaphylaxis to etoposide not remediable by premedication * Not pregnant or nursing * Fertile patients must use effective contraception * Third percentile weight for height PRIOR CONCURRENT THERAPY: * At least 4 weeks since chemotherapy and recovered * Prior cumulative anthracycline dose no greater than 360 mg per square meter * Hydroxyurea therapy allowed just prior to study for rapidly rising blast count
References
Publications (2)
- RESULTO'Brien MM, Lacayo NJ, Lum BL, Kshirsagar S, Buck S, Ravindranath Y, Bernstein M, Weinstein H, Chang MN, Arceci RJ, Sikic BI, Dahl GV. Phase I study of valspodar (PSC-833) with mitoxantrone and etoposide in refractory and relapsed pediatric acute leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2010 May;54(5):694-702. doi: 10.1002/pbc.22366. PMID 20209646
- RESULTLacayo NJ, Lum BL, Chin DL, et al.: Pharmacokinetics of mitoxantrone in a Phase I Trial of PSC-833 (Valspodar) as an MDR1/Pg-P modulator in acute myeloid leukemia (AML) from the children's oncology group (COG). [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1583, 2002.