Combination Chemotherapy Plus PSC-833 in Treating Children With Refractory or Relapsed Acute Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00002912
First received: November 1, 1999
Last updated: January 31, 2013
Last verified: August 2010
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: etoposide
Drug: mitoxantrone hydrochloride
Drug: valspodar
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE I COOPERATIVE AGREEMENT PEDIATRIC TRIAL OF MITOXANTRONE, ETOPOSIDE AND PSC-833 (PSC-ME) THERAPY IN PATIENTS WITH RELAPSED AND REFRACTORY ACUTE LEUKEMIA

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Enrollment: 3
Study Start Date: January 1997
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Drug: etoposide Drug: mitoxantrone hydrochloride Drug: valspodar

Detailed Description:

OBJECTIVES:

I. Determine the maximum tolerated dose of PSC-833 in combination with mitoxantrone and etoposide in children with refractory or relapsed acute leukemia.

II. Determine the effects of PSC-833 on mitoxantrone and etoposide pharmacokinetics.

III. Quantify MDR1 gene expression and MDR1 P-glycoprotein expression and function in patient-derived leukemia cells.

OUTLINE: This is a dose escalation study of PSC-833.

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002912

  Show 55 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Gary V.H. Dahl, MD Lucile Packard Children's Hospital at Stanford University Medical Center
  More Information

Additional Information:
Publications:
Lacayo 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.

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00002912     History of Changes
Other Study ID Numbers: NCI-2012-01835, POG-9423, CCG-P9423, CDR0000065285
Study First Received: November 1, 1999
Last Updated: January 31, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia

Additional relevant MeSH terms:
Leukemia
Neoplasms by Histologic Type
Neoplasms
Etoposide
Etoposide phosphate
Mitoxantrone
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 23, 2014