Combination Chemotherapy With or Without PSC 833, Peripheral Stem Cell Transplantation, and/or Interleukin-2 in Treating Patients With Acute Myeloid Leukemia

NCT00006363 | Completed Phase 3

• 3 other identifiers: NCI-2012-02824CALGB-19808U10CA031946
• Study Type: interventional
• Target: 720
• Locations: 1 country
• Sites: 1

Brief Summary

Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PSC 833 may increase the effectiveness of chemotherapy by making cancer cells more sensitive to the drugs. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. This randomized phase III trial is studying giving combination chemotherapy together with PSC 833 followed by a peripheral stem cell transplant with or without interleukin-2 to see how well it works compared to combination chemotherapy alone followed by a peripheral stem cell transplant with or without interleukin-2 in treating patients with acute myeloid leukemia.

Conditions

Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Outcome Measures

Primary Outcomes (2)

• Disease-free survival

  An unstratified logrank test for the induction treatment comparison and a stratified logrank test for the post-remission treatment comparison will be the primary statistical methods used for treatment comparisons.

  Up to 10 years

• Overall survival

  An unstratified logrank test for the induction treatment comparison and a stratified logrank test for the post-remission treatment comparison will be the primary statistical methods used for treatment comparisons.

  Up to 10 years

Secondary Outcomes (3)

• Estimates of disease-free survival curves

  Up to 10 years

• Estimates of overall survival curves

  Up to 10 years

• Toxicities and adverse events assessed using National Cancer Institute (NCI) Common Toxicity Criteria (CTC)

  Up to 10 years

Study Arms (7)

Induction Arm I

EXPERIMENTAL

Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV over 5-10 minutes followed by etoposide IV over 2 hours on days 1-3. Patients with 20% or greater bone marrow cellularity and greater than 5% leukemia blasts at the end of the first course receive a second course of cytarabine IV continuously on days 1-5 and daunorubicin IV over 5-10 minutes followed by etoposide IV over 2 hours on days 1 and 2.

Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: etoposide; Other: pharmacological study

Induction Arm II

EXPERIMENTAL

Patients receive PSC 833 IV continuously on days 1-3 and cytarabine, daunorubicin, and etoposide as in arm I. Patients with 20% or greater bone marrow cellularity and greater than 5% leukemia blasts at the end of the first course receive a second course of PSC 833 IV continuously on days 1 and 2 and cytarabine, daunorubicin, and etoposide as in arm I.

Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: etoposide; Drug: valspodar; Other: pharmacological study

Intensification Favorable

EXPERIMENTAL

Patients receive HiDAC IV over 3 hours every 12 hours on days 1, 3, and 5. Treatment repeats no earlier than 28 days after the prior course and no later than 14 days after hematopoietic recovery for two more courses.

Drug: cytarabine; Other: pharmacological study

Intensification Unfavorable PBSCT Group

EXPERIMENTAL

Patients receive etoposide IV continuously and HiDAC IV over 2 hours every 12 hours on days 1-4. Patients also receive G-CSF SC daily beginning on day 14 and continuing until PBSC collection is completed. Patients who are not able to undergo PBSCT after HiDAC/etoposide continue treatment in the non-PBSCT group. At least 4 weeks after HiDAC/etoposide recovery, patients receive oral busulfan every 6 hours on days -7 to -4 and etoposide IV over 4 hours on day -3 prior to PBSCT. Patients receive autologous PBSC infusion on day 0. Patients also receive G-CSF SC beginning on day 0 and continuing until hematopoietic recovery.

Drug: cytarabine; Drug: etoposide; Biological: filgrastim; Drug: busulfan; Procedure: autologous hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Other: pharmacological study

Intensification Unfavorable Non-PBSCT Group

EXPERIMENTAL

Patients receive etoposide, HiDAC, and G-CSF as in the PBSCT group. After hematopoietic recovery, patients then receive HiDAC IV over 3 hours every 12 hours on days 1, 3, and 5. Treatment repeats no earlier than 28 days after prior course and no later than 14 days after hematopoietic recovery for one more course.

Drug: cytarabine; Drug: etoposide; Biological: filgrastim; Other: pharmacological study

Immunotherapy Arm I

EXPERIMENTAL

Patients begin therapy no later than 120 days after the first day of the last course of HiDAC treatment OR day 0 of PBSCT. Patients receive low-dose IL-2 SC on days 1-14, 19-28, 33-42, 47-56, 61-70, and 75-90. In addition, patients receive high-dose IL-2 SC on days 15-17, 29-31, 43-45, 57-59, and 71-73.

Biological: aldesleukin; Other: pharmacological study

Immunotherapy Arm II

ACTIVE COMPARATOR

Patients are observed and receive no further therapy.

Other: clinical observation; Other: pharmacological study

Interventions

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Induction Arm I; Induction Arm II; Intensification Favorable; Intensification Unfavorable Non-PBSCT Group; Intensification Unfavorable PBSCT Group

daunorubicin hydrochloride DRUG

Given IV

Also known as: Cerubidin, Cerubidine, daunomycin hydrochloride, daunorubicin, RP-13057

Induction Arm I; Induction Arm II

etoposide DRUG

Given IV

Also known as: EPEG, VP-16, VP-16-213

Induction Arm I; Induction Arm II; Intensification Unfavorable Non-PBSCT Group; Intensification Unfavorable PBSCT Group

valspodar DRUG

Given IV

Also known as: Amdray, PSC 833

Induction Arm II

filgrastim BIOLOGICAL

Given SC

Also known as: G-CSF, Neupogen

Intensification Unfavorable Non-PBSCT Group; Intensification Unfavorable PBSCT Group

busulfan DRUG

Given orally

Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon

Intensification Unfavorable PBSCT Group

autologous hematopoietic stem cell transplantation PROCEDURE

Undergo autologous PBSCT

Intensification Unfavorable PBSCT Group

peripheral blood stem cell transplantation PROCEDURE

Undergo autologous PBSCT

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Intensification Unfavorable PBSCT Group

aldesleukin BIOLOGICAL

Given SC

Also known as: IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

Immunotherapy Arm I

clinical observation OTHER

Undergo clinical observation

Also known as: observation

Immunotherapy Arm II

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Immunotherapy Arm I; Immunotherapy Arm II; Induction Arm I; Induction Arm II; Intensification Favorable; Intensification Unfavorable Non-PBSCT Group; Intensification Unfavorable PBSCT Group

Eligibility Criteria

• Age: 15 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Unequivocal histologic diagnosis of AML (\> 20% blasts in the bone marrow based on the World Health Organization \[WHO\] and/or French-American-British Cooperative group \[FAB\] classifications), excluding M3 (acute promyelocytic leukemia); patients with antecedent myelodysplasia are eligible for treatment on this trial only if there was no bone marrow biopsy showing myelodysplastic syndrome (MDS) \> 3 months prior to enrollment; patients with therapy-related MDS or therapy-related AML or a chronic myeloproliferative disorder are not eligible
• No prior treatment for leukemia or myelodysplasia with four permissible exceptions:
• Emergency leukapheresis
• Emergency treatment for hyperleukocytosis with hydroxyurea
• Cranial radiation therapy (RT) for central nervous system (CNS) leukostasis (one dose only)
• Growth factor/cytokine support

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

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.

  PMID: 36184192 DERIVED

• 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.

  PMID: 31375516 DERIVED

• Kolitz JE, George SL, Marcucci G, Vij R, Powell BL, Allen SL, DeAngelo DJ, Shea TC, Stock W, Baer MR, Hars V, Maharry K, Hoke E, Vardiman JW, Bloomfield CD, Larson RA; Cancer and Leukemia Group B. P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808. Blood. 2010 Sep 2;116(9):1413-21. doi: 10.1182/blood-2009-07-229492. Epub 2010 Jun 3.

  PMID: 20522709 DERIVED

MeSH Terms

Conditions

Leukemia, Basophilic, Acute; Leukemia, Eosinophilic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute

Interventions

Cytarabine; Daunorubicin; Etoposide; valspodar; Filgrastim; Granulocyte Colony-Stimulating Factor; Busulfan; Peripheral Blood Stem Cell Transplantation; aldesleukin; Interleukin-2; Watchful Waiting; Observation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Interleukins; Lymphokines; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Methods; Investigative Techniques

Study Officials

• Jonathan Kolitz

  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: October 4, 2000
• First Posted: January 27, 2003
• Study Start: November 1, 2000
• Primary Completion: June 1, 2005
• Last Updated: June 4, 2013

Record last verified: 2013-06

Locations

US (1)