Imatinib Mesylate With or Without Interferon Alfa or Cytarabine Compared With Interferon Alfa Followed by Donor Stem Cell Transplant in Treating Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia

NCT00055874 | Completed Phase 3

• 3 other identifiers: III-MK-CML-IVCDR0000271424EU-20248
• Study Type: interventional
• Target: 1,551
• Locations: 2 countries
• Sites: 66

Brief Summary

RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, imatinib mesylate may stop the growth of cancer cells by blocking the enzymes needed for cancer cell growth. Interferon alfa may interfere with the growth of cancer cells and slow the growth of cancer. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known which treatment regimen is most effective in treating chronic phase chronic myelogenous leukemia. PURPOSE: This randomized phase III trial is studying imatinib mesylate with or without interferon alfa or cytarabine to see how well it works compared with interferon alfa followed by donor stem cell transplant in treating patients with newly diagnosed chronic phase chronic myelogenous leukemia.

Conditions

Leukemia

Keywords

chronic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; chronic myelogenous leukemia, BCR-ABL1 positive

Outcome Measures

Primary Outcomes (4)

• Overall survival

• Risk group-dependent survival

• Progression-free survival

• Hematologic, cytogenetic, and molecular response rates

Secondary Outcomes (2)

• Adverse drug effects

• Quality of life

Interventions

recombinant interferon alfa BIOLOGICAL

cytarabine DRUG

hydroxyurea DRUG

imatinib mesylate DRUG

allogeneic bone marrow transplantation PROCEDURE

autologous bone marrow transplantation PROCEDURE

peripheral blood stem cell transplantation PROCEDURE

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Newly diagnosed chronic phase chronic myelogenous leukemia (CML) * bcr-abl positive * No blasts, promyelocytes, myelocytes, or metamyelocytes in the peripheral blood * Availability of a HLA-identical sibling or unrelated donor PATIENT CHARACTERISTICS: Age * Any age Performance status * Not specified Life expectancy * Not specified Hematopoietic * Not specified Hepatic * Not specified Renal * Not specified Other * Not pregnant or nursing * Fertile patients must use effective contraception * No second malignancy requiring therapy * No evidence of disease-related symptoms or extramedullary disease (including hepatosplenomegaly) * No serious diseases that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy * No prior interferon Chemotherapy * No prior chemotherapy other than hydroxyurea Endocrine therapy * Not specified Radiotherapy * No prior radiotherapy Surgery * Not specified Other * Prior anagrelide allowed * No participation in another clinical trial

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Heidelberg University: lead

Study Sites (66)

Krankenhaus / Klinikum Krefeld

Aachen, 52074, Germany

Location

Kreiskrankenhaus Aurich

Aurich, 26603, Germany

Location

Kreiskrankenhaus

Bad Hersfeld, 36251, Germany

Location

St. Hedwig Krankenhaus

Berlin, 10115, Germany

Location

Haematologisch-Onkologische Schwerpunktpraxis

Berlin, 13357, Germany

Location

Schwerpunktpraxis fuer Haematologie und Internistische Onkologie

Berlin, D-10117, Germany

Location

Gemeinschaftspraxis fuer Haematologie und Internistische Onkologie

Berlin, D-12103, Germany

Location

Onkologische Schwerpunktpraxis Bielefeld

Bielefeld, D-33602, Germany

Location

Augustinum

Bonn, D-53117, Germany

Location

Hamatologische Sprechstunde

Brandenburg, 14770, Germany

Location

Praxis Dres. F.& G. Doering

Bremen, D-28205, Germany

Location

Staedtisches Kliniken Delmenhorst

Delmenhorst, 27753, Germany

Location

Universitaetsklinikum Essen

Essen, D-45122, Germany

Location

Evangelisches Krankenhaus Essen Werden

Essen, D-45239, Germany

Location

Klinikum der J.W. Goethe Universitaet

Frankfurt, D-60590, Germany

Location

Internistische Praxisgemeinschaft

Germering, 82110, Germany

Location

DR Herbert - Nieper Krankenhaus Goslar

Goslar, 38642, Germany

Location

Universitaetsklinikum Goettingen

Göttingen, D-37075, Germany

Location

St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH

Hagen, D-58095, Germany

Location

Asklepios Klinik St. Georg

Hamburg, D-20099, Germany

Location

University Medical Center Hamburg - Eppendorf

Hamburg, D-20246, Germany

Location

Evangelische Krankenhaus Hamm

Hamm, DOH-59063, Germany

Location

Medizinische Universitaetsklinik und Poliklinik

Heidelberg, 69115, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, 69115, Germany

Location

Ruprecht - Karls - Universitaet Heidelberg

Heidelberg, D-69120, Germany

Location

Medical University Hospital Homburg

Homburg, 66421, Germany

Location

Universitaetsklinikum des Saarlandes

Homburg, D-66424, Germany

Location

Westpfalz-Klinikum GmbH

Kaiserslautern, D-67653, Germany

Location

Staedtisches Klinikum Karlsruhe gGmbH

Karlsruhe, 76133, Germany

Location

St. Vincentius - Kliniken

Karlsruhe, D-76137, Germany

Location

Klinikum Kempten Oberallgaeu

Kempten, 87439, Germany

Location

University Hospital Schleswig-Holstein - Kiel Campus

Kiel, D-24116, Germany

Location

Klinikum Krefeld GmbH

Krefeld, D-47805, Germany

Location

Internistisches Fachaerzte Zentrum Langen

Langen, D-63225, Germany

Location

Caritas - Krakenhaus Lebach

Lebach, 66822, Germany

Location

Onkologische Schwerpunktpraxis - Leer

Leer, D-26789, Germany

Location

Klinikum Lippe - Lemgo

Lemgo, D-32657, Germany

Location

Klinikum der Stadt Ludwigshafen am Rhein

Ludwigshafen am Rhein, D-67063, Germany

Location

III Medizinische Klinik Mannheim

Mannheim, D-68305, Germany

Location

Hospital Maria-Hilf II

Mönchengladbach, D-41063, Germany

Location

Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, D-81377, Germany

Location

Haematologische Schwerpunktpraxis

Munich, D-81679, Germany

Location

Krankenhaus Muenchen Schwabing

München, 80804, Germany

Location

Haematologisch - Onkologische Gemeinschaftspraxis - Muenster

Münster, D-48149, Germany

Location

Hematologische Onkologische Praxis

Regensburg, 93047, Germany

Location

Klinikum der Universitaet Regensburg

Regensburg, D-93042, Germany

Location

Klinikum Remscheid GmbH

Remscheid, D-42859, Germany

Location

Internistische Schwerpunktpraxis

Rüsselsheim am Main, 65428, Germany

Location

Diakonie - Krankenhaus

Schwäbisch Hall, 74523, Germany

Location

St. Marien - Krankenhaus Siegen GMBH

Siegen, D-57072, Germany

Location

Kreiskrankenhaus Siegen

Siegen, D-57076, Germany

Location

Hanse-Klinikum Stralsund - Krankenhaus West

Stralsund, D-18410, Germany

Location

Onkologische Schwerpunktpraxis - Straubing

Straubing, 94315, Germany

Location

Robert-Bosch-Krankenhaus

Stuttgart, 70376, Germany

Location

Haematologische Praxis

Stuttgart, D-70173, Germany

Location

Klinik fuer Onkologie - Katharinenhospital Stuttgart

Stuttgart, D-70174, Germany

Location

Diakonie Klinikum Stuttgart

Stuttgart, D-70176, Germany

Location

Unknown Facility

Trier, D-54290, Germany

Location

Schwerpunktpraxis fuer Rheumatologie und Haematologie/Internistische Onkologie

Tübingen, D-72072, Germany

Location

Southwest German Cancer Center at Eberhard-Karls-University

Tübingen, D-72076, Germany

Location

Haematologische Praxis

Weiden, D-92637, Germany

Location

Praxis Fuer Haemotologie Und Internistischer Onkologie

Wuppertal, 42105, Germany

Location

Helios Kliniken Wuppertal University Hospital

Wuppertal, D-42283, Germany

Location

Hamatologisch - Onkologische Praxis Wurzburg

Würzburg, 97070, Germany

Location

University Wurzburg

Würzburg, D-97070, Germany

Location

Unknown Facility

Basel, CH 4051, Switzerland

Location

Related Publications (11)

• Hehlmann R, Lauseker M, Jung-Munkwitz S, Leitner A, Muller MC, Pletsch N, Proetel U, Haferlach C, Schlegelberger B, Balleisen L, Hanel M, Pfirrmann M, Krause SW, Nerl C, Pralle H, Gratwohl A, Hossfeld DK, Hasford J, Hochhaus A, Saussele S. Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-alpha in newly diagnosed chronic myeloid leukemia. J Clin Oncol. 2011 Apr 20;29(12):1634-42. doi: 10.1200/JCO.2010.32.0598. Epub 2011 Mar 21.

  PMID: 21422420 RESULT

• Burchert A, Muller MC, Kostrewa P, Erben P, Bostel T, Liebler S, Hehlmann R, Neubauer A, Hochhaus A. Sustained molecular response with interferon alfa maintenance after induction therapy with imatinib plus interferon alfa in patients with chronic myeloid leukemia. J Clin Oncol. 2010 Mar 10;28(8):1429-35. doi: 10.1200/JCO.2009.25.5075. Epub 2010 Feb 8.

  PMID: 20142590 RESULT

• Saussele S, Lauseker M, Gratwohl A, Beelen DW, Bunjes D, Schwerdtfeger R, Kolb HJ, Ho AD, Falge C, Holler E, Schlimok G, Zander AR, Arnold R, Kanz L, Dengler R, Haferlach C, Schlegelberger B, Pfirrmann M, Muller MC, Schnittger S, Leitner A, Pletsch N, Hochhaus A, Hasford J, Hehlmann R; German CML Study Group. Allogeneic hematopoietic stem cell transplantation (allo SCT) for chronic myeloid leukemia in the imatinib era: evaluation of its impact within a subgroup of the randomized German CML Study IV. Blood. 2010 Mar 11;115(10):1880-5. doi: 10.1182/blood-2009-08-237115. Epub 2009 Nov 18.

  PMID: 19965667 RESULT

• Saussele S, Hehlmann R, Fabarius A, Jeromin S, Proetel U, Rinaldetti S, Kohlbrenner K, Einsele H, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Oppliger Leibundgut E, Heim D, Krause SW, Hofmann WK, Hasford J, Pfirrmann M, Muller MC, Hochhaus A, Lauseker M. Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV. Leukemia. 2018 May;32(5):1222-1228. doi: 10.1038/s41375-018-0055-7. Epub 2018 Feb 26.

  PMID: 29479070 DERIVED

• Saussele S, Krauss MP, Hehlmann R, Lauseker M, Proetel U, Kalmanti L, Hanfstein B, Fabarius A, Kraemer D, Berdel WE, Bentz M, Staib P, de Wit M, Wernli M, Zettl F, Hebart HF, Hahn M, Heymanns J, Schmidt-Wolf I, Schmitz N, Eckart MJ, Gassmann W, Bartholomaus A, Pezzutto A, Leibundgut EO, Heim D, Krause SW, Burchert A, Hofmann WK, Hasford J, Hochhaus A, Pfirrmann M, Muller MC; Schweizerische Arbeitsgemeinschaft fur Klinische Krebsforschung and the German CML Study Group. Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML study IV. Blood. 2015 Jul 2;126(1):42-9. doi: 10.1182/blood-2015-01-617993. Epub 2015 Apr 27.

  PMID: 25918346 DERIVED

• Lauseker M, Hasford J, Hoffmann VS, Muller MC, Hehlmann R, Pfirrmann M; German CML Study Group. A multi-state model approach for prediction in chronic myeloid leukaemia. Ann Hematol. 2015 Jun;94(6):919-27. doi: 10.1007/s00277-014-2246-2. Epub 2014 Dec 3.

  PMID: 25465231 DERIVED

• Hanfstein B, Lauseker M, Hehlmann R, Saussele S, Erben P, Dietz C, Fabarius A, Proetel U, Schnittger S, Haferlach C, Krause SW, Schubert J, Einsele H, Hanel M, Dengler J, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Baerlocher GM, Pfirrmann M, Hasford J, Hofmann WK, Hochhaus A, Muller MC; SAKK and the German CML Study Group. Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib. Haematologica. 2014 Sep;99(9):1441-7. doi: 10.3324/haematol.2013.096537. Epub 2014 May 16.

  PMID: 24837466 DERIVED

• Proetel U, Pletsch N, Lauseker M, Muller MC, Hanfstein B, Krause SW, Kalmanti L, Schreiber A, Heim D, Baerlocher GM, Hofmann WK, Lange E, Einsele H, Wernli M, Kremers S, Schlag R, Muller L, Hanel M, Link H, Hertenstein B, Pfirrman M, Hochhaus A, Hasford J, Hehlmann R, Saussele S; German Chronic Myeloid Leukemia Study Group; Schweizerische Arbeitsgemeinschaft fur Klinische Krebsforschung (SAKK). Older patients with chronic myeloid leukemia (>/=65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV. Ann Hematol. 2014 Jul;93(7):1167-76. doi: 10.1007/s00277-014-2041-0.

  PMID: 24658964 DERIVED

• Lauseker M, Hasford J, Pfirrmann M, Hehlmann R; German CML Study Group. The impact of health care settings on survival time of patients with chronic myeloid leukemia. Blood. 2014 Apr 17;123(16):2494-6. doi: 10.1182/blood-2013-11-539742. Epub 2014 Mar 12.

  PMID: 24622328 DERIVED

• Hehlmann R, Muller MC, Lauseker M, Hanfstein B, Fabarius A, Schreiber A, Proetel U, Pletsch N, Pfirrmann M, Haferlach C, Schnittger S, Einsele H, Dengler J, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Baerlocher GM, Ehninger G, Heim D, Heimpel H, Nerl C, Krause SW, Hossfeld DK, Kolb HJ, Hasford J, Saussele S, Hochhaus A. Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV. J Clin Oncol. 2014 Feb 10;32(5):415-23. doi: 10.1200/JCO.2013.49.9020. Epub 2013 Dec 2.

  PMID: 24297946 DERIVED

• Kalmanti L, Saussele S, Lauseker M, Proetel U, Muller MC, Hanfstein B, Schreiber A, Fabarius A, Pfirrmann M, Schnittger S, Dengler J, Falge C, Kanz L, Neubauer A, Stegelmann F, Pfreundschuh M, Waller CF, Spiekermann K, Krause SW, Heim D, Nerl C, Hossfeld DK, Kolb HJ, Hochhaus A, Hasford J, Hehlmann R; German Chronic Myeloid Leukemia Study Group; Schweizerische Arbeitsgemeinschaft fur Klinische Krebsforschung (SAKK). Younger patients with chronic myeloid leukemia do well in spite of poor prognostic indicators: results from the randomized CML study IV. Ann Hematol. 2014 Jan;93(1):71-80. doi: 10.1007/s00277-013-1937-4. Epub 2013 Oct 27.

  PMID: 24162333 DERIVED

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Interferon-alpha; Cytarabine; Hydroxyurea; Imatinib Mesylate; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Urea; Amides; Organic Chemicals; Benzamides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Ruediger Hehlmann, MD

  III. Medizinische Klinik Mannheim

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Study Record Dates

• First Submitted: March 6, 2003
• First Posted: March 7, 2003
• Study Start: June 1, 2002
• Primary Completion: March 31, 2012
• Study Completion: March 31, 2017
• Last Updated: May 3, 2018

Record last verified: 2011-11

Locations

CH (1); DE (65)