NCT00003190

Brief Summary

Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without PSC 833 followed by interleukin-2 or no further therapy in treating older patients who have acute myeloid leukemia. Some cancers become resistant to chemotherapy drugs. Combining PSC 833 with more than one chemotherapy drug may reduce resistance to the drugs and allow the cancer cells to be killed. Combining interleukin-2 with combination chemotherapy plus PSC 833 may kill more cancer cells.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
640

participants targeted

Target at P75+ for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 1998

Completed
1.8 years until next milestone

First Submitted

Initial submission to the registry

November 1, 1999

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2002

Completed
1.2 years until next milestone

First Posted

Study publicly available on registry

October 28, 2003

Completed
Last Updated

June 4, 2013

Status Verified

June 1, 2013

Enrollment Period

4.6 years

First QC Date

November 1, 1999

Last Update Submit

June 3, 2013

Conditions

Outcome Measures

Primary Outcomes (2)

  • Disease-free survival

    Analyzed by intention to treat.

    From second randomization to relapse or death, assessed up to 10 years

  • Overall survival

    Up to 10 years

Study Arms (2)

Arm I (cytarabine, daunorubicin, etoposide)

EXPERIMENTAL

Patients receive cytarabine IV continuously over 7 days and daunorubicin IV bolus followed by etoposide IV over 2 hours on days 1-3.

Drug: cytarabineDrug: daunorubicin hydrochlorideDrug: etoposide

Arm II (valspodar, daunorubicin, etoposide, cytarabine)

EXPERIMENTAL

Patients receive treatment as in arm I with the addition of PSC 833 induction. A loading dose of PSC 833 IV is given over 2 hours, followed by a 74-hour continuous infusion of PSC 833 beginning 2 hours before daunorubicin and etoposide. Patients may receive a second induction course if residual leukemia is present in the bone marrow. Patients who experience a CR and meet certain other criteria receive postremission chemotherapy consisting of cytarabine IV continuously over 5 days plus daunorubicin IV followed by etoposide IV over 2 hours on days 1 and 2. Patients who are randomized to receive PSC 833 during induction chemotherapy receive a loading dose of PSC 833 before beginning a 48-hour continuous infusion of PSC 833 concurrently with cytarabine/daunorubicin/etoposide postremission chemotherapy. After completing postremission chemotherapy, patients are randomized to a no further treatment group or IL-2 immunotherapy.

Drug: cytarabineDrug: daunorubicin hydrochlorideDrug: etoposideDrug: valspodar

Interventions

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside
Arm I (cytarabine, daunorubicin, etoposide)Arm II (valspodar, daunorubicin, etoposide, cytarabine)

Given IV

Also known as: Cerubidin, Cerubidine, daunomycin hydrochloride, daunorubicin, RP-13057
Arm I (cytarabine, daunorubicin, etoposide)Arm II (valspodar, daunorubicin, etoposide, cytarabine)

Given IV

Also known as: EPEG, VP-16, VP-16-213
Arm I (cytarabine, daunorubicin, etoposide)Arm II (valspodar, daunorubicin, etoposide, cytarabine)

Given IV

Also known as: Amdray, PSC 833
Arm II (valspodar, daunorubicin, etoposide, cytarabine)

Eligibility Criteria

Age60 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Unequivocal histologic diagnosis of AML, FAB classification (M0-M7), excluding M3 (acute promyelocytic leukemia); patients with a history of antecedent myelodysplasia remain eligible for treatment on this trial
  • No prior treatment for acute leukemia or myelodysplasia with four permissible exceptions:
  • Emergency leukapheresis;
  • Emergency treatment for hyperleukocytosis with hyroxyurea;
  • Cranial RT for CNS leukostasis (one dose only);
  • Growth factor/cytokine support.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cancer and Leukemia Group B

Chicago, Illinois, 60606, United States

Location

Related Publications (3)

  • Seffernick AE, Mrozek K, Nicolet D, Stone RM, Eisfeld AK, Byrd JC, Archer KJ. High-dimensional genomic feature selection with the ordered stereotype logit model. Brief Bioinform. 2022 Nov 19;23(6):bbac414. doi: 10.1093/bib/bbac414.

  • Mims AS, Kohlschmidt J, Borate U, Blachly JS, Orwick S, Eisfeld AK, Papaioannou D, Nicolet D, Mromicronzek K, Stein E, Bhatnagar B, Stone RM, Kolitz JE, Wang ES, Powell BL, Burd A, Levine RL, Druker BJ, Bloomfield CD, Byrd JC. A precision medicine classification for treatment of acute myeloid leukemia in older patients. J Hematol Oncol. 2021 Jun 23;14(1):96. doi: 10.1186/s13045-021-01110-5.

  • Walker CJ, Kohlschmidt J, Eisfeld AK, Mrozek K, Liyanarachchi S, Song C, Nicolet D, Blachly JS, Bill M, Papaioannou D, Oakes CC, Giacopelli B, Genutis LK, Maharry SE, Orwick S, Archer KJ, Powell BL, Kolitz JE, Uy GL, Wang ES, Carroll AJ, Stone RM, Byrd JC, de la Chapelle A, Bloomfield CD. Genetic Characterization and Prognostic Relevance of Acquired Uniparental Disomies in Cytogenetically Normal Acute Myeloid Leukemia. Clin Cancer Res. 2019 Nov 1;25(21):6524-6531. doi: 10.1158/1078-0432.CCR-19-0725. Epub 2019 Aug 2.

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, AcuteLeukemia, Monocytic, AcuteLeukemia, Myeloid, AcuteCongenital AbnormalitiesLeukemia, Myelomonocytic, AcuteLeukemia, Erythroblastic, Acute

Interventions

CytarabineDaunorubicinEtoposidevalspodar

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMyeloproliferative DisordersBone Marrow Diseases

Intervention Hierarchy (Ancestors)

CytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsArabinonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesPodophyllotoxinTetrahydronaphthalenesNaphthalenesGlucosides

Study Officials

  • Maria Baer

    Cancer and Leukemia Group B

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 1, 1999

First Posted

October 28, 2003

Study Start

January 1, 1998

Primary Completion

August 1, 2002

Last Updated

June 4, 2013

Record last verified: 2013-06

Locations