AzTrials
AzTrials

LeukemiaPhase 3NCT00055874

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

A Phase 3 study testing recombinant interferon alfa, cytarabine and hydroxyurea in people with Leukemia, run by Heidelberg University at 66 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Leukemia
What is being tested?
recombinant interferon alfa, cytarabine and hydroxyurea
Type of treatment
Surgery or procedure
How many people
1,551 participants
Where
66 sitesin 2 countries
Study dates
Jun 2002to 31 Mar 2017
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

66 sites in 2 countries.

66 sites in 2 countries

Germany65 sites

  • Krankenhaus / Klinikum Krefeld

    Aachen, 52074

  • Kreiskrankenhaus Aurich

    Aurich, 26603

  • Kreiskrankenhaus

    Bad Hersfeld, 36251

  • St. Hedwig Krankenhaus

    Berlin, 10115

  • Haematologisch-Onkologische Schwerpunktpraxis

    Berlin, 13357

  • Schwerpunktpraxis fuer Haematologie und Internistische Onkologie

    Berlin, D-10117

  • Gemeinschaftspraxis fuer Haematologie und Internistische Onkologie

    Berlin, D-12103

  • Onkologische Schwerpunktpraxis Bielefeld

    Bielefeld, D-33602

  • Augustinum

    Bonn, D-53117

  • Hamatologische Sprechstunde

    Brandenburg, 14770

  • Praxis Dres. F.& G. Doering

    Bremen, D-28205

  • Staedtisches Kliniken Delmenhorst

    Delmenhorst, 27753

  • Universitaetsklinikum Essen

    Essen, D-45122

  • Evangelisches Krankenhaus Essen Werden

    Essen, D-45239

  • Klinikum der J.W. Goethe Universitaet

    Frankfurt, D-60590

  • Internistische Praxisgemeinschaft

    Germering, 82110

  • DR Herbert - Nieper Krankenhaus Goslar

    Goslar, 38642

  • Universitaetsklinikum Goettingen

    Göttingen, D-37075

  • St. Marien Hospital - Katholisches Krankenhaus Hagen gGmbH

    Hagen, D-58095

  • Asklepios Klinik St. Georg

    Hamburg, D-20099

  • University Medical Center Hamburg - Eppendorf

    Hamburg, D-20246

  • Evangelische Krankenhaus Hamm

    Hamm, DOH-59063

  • Medizinische Universitaetsklinik und Poliklinik

    Heidelberg, 69115

  • Universitatsklinikum Heidelberg

    Heidelberg, 69115

  • Ruprecht - Karls - Universitaet Heidelberg

    Heidelberg, D-69120

  • Medical University Hospital Homburg

    Homburg, 66421

  • Universitaetsklinikum des Saarlandes

    Homburg, D-66424

  • Westpfalz-Klinikum GmbH

    Kaiserslautern, D-67653

  • Staedtisches Klinikum Karlsruhe gGmbH

    Karlsruhe, 76133

  • St. Vincentius - Kliniken

    Karlsruhe, D-76137

  • Klinikum Kempten Oberallgaeu

    Kempten, 87439

  • University Hospital Schleswig-Holstein - Kiel Campus

    Kiel, D-24116

  • Klinikum Krefeld GmbH

    Krefeld, D-47805

  • Internistisches Fachaerzte Zentrum Langen

    Langen, D-63225

  • Caritas - Krakenhaus Lebach

    Lebach, 66822

  • Onkologische Schwerpunktpraxis - Leer

    Leer, D-26789

  • Klinikum Lippe - Lemgo

    Lemgo, D-32657

  • Klinikum der Stadt Ludwigshafen am Rhein

    Ludwigshafen am Rhein, D-67063

  • III Medizinische Klinik Mannheim

    Mannheim, D-68305

  • Hospital Maria-Hilf II

    Mönchengladbach, D-41063

  • Krankenhaus Muenchen Schwabing

    München, 80804

  • Klinikum der Universitaet Muenchen - Grosshadern Campus

    Munich, D-81377

  • Haematologische Schwerpunktpraxis

    Munich, D-81679

  • Haematologisch - Onkologische Gemeinschaftspraxis - Muenster

    Münster, D-48149

  • Hematologische Onkologische Praxis

    Regensburg, 93047

  • Klinikum der Universitaet Regensburg

    Regensburg, D-93042

  • Klinikum Remscheid GmbH

    Remscheid, D-42859

  • Internistische Schwerpunktpraxis

    Rüsselsheim am Main, 65428

  • Diakonie - Krankenhaus

    Schwäbisch Hall, 74523

  • St. Marien - Krankenhaus Siegen GMBH

    Siegen, D-57072

  • Kreiskrankenhaus Siegen

    Siegen, D-57076

  • Hanse-Klinikum Stralsund - Krankenhaus West

    Stralsund, D-18410

  • Onkologische Schwerpunktpraxis - Straubing

    Straubing, 94315

  • Robert-Bosch-Krankenhaus

    Stuttgart, 70376

  • Haematologische Praxis

    Stuttgart, D-70173

  • Klinik fuer Onkologie - Katharinenhospital Stuttgart

    Stuttgart, D-70174

  • Diakonie Klinikum Stuttgart

    Stuttgart, D-70176

  • Study site

    Trier, D-54290

  • Schwerpunktpraxis fuer Rheumatologie und Haematologie/Internistische Onkologie

    Tübingen, D-72072

  • Southwest German Cancer Center at Eberhard-Karls-University

    Tübingen, D-72076

  • Haematologische Praxis

    Weiden, D-92637

  • Praxis Fuer Haemotologie Und Internistischer Onkologie

    Wuppertal, 42105

  • Helios Kliniken Wuppertal University Hospital

    Wuppertal, D-42283

  • Hamatologisch - Onkologische Praxis Wurzburg

    Würzburg, 97070

  • University Wurzburg

    Würzburg, D-97070

Other trials in Germany

Switzerland1 site

  • Study site

    Basel, CH 4051

Other trials in Switzerland

About this study

Official title: Treatment Optimization Trial in Chronic Myeloid Leukemia (CML) - Randomized Controlled Comparison of Imatinib vs. Imatinib/Interferon-alpha vs. Imatinib/Low-Dose AraC vs. Interferon-alpha Standard Therapy and Determination of the Role of Allografting in Newly Diagnosed Chronic Phase

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.

Read the detailed description

OBJECTIVES:

  • Compare the hematologic, cytogenetic, and molecular response rates in patients with newly diagnosed chronic phase chronic myelogenous leukemia treated with imatinib mesylate alone or with interferon alfa or low-dose cytarabine vs interferon alfa standard therapy.
  • Compare the group-dependent, progression-free and overall survival and time to progression in patients treated with these regimens.
  • Compare the efficacy of allogeneic stem cell transplantation vs imatinib mesylate-based therapy in patients eligible for transplantation.
  • Compare the efficacy of reduced-intensity conditioning vs standard conditioning in patients over 45 years of age.
  • Determine the time to and duration of hematologic, cytogenetic, and molecular responses and correlate these factors in patients treated with these regimens.
  • Compare the short- and long-term adverse effects of these regimens in these patients.
  • Compare the presentation, duration, and responses to therapy of accelerated and blastic phases in patients treated with these regimens.
  • Determine the survival of high-risk patients after early allografting.
  • Determine the influence of pre-transplantation therapies on the outcome of allogeneic stem cell transplantation in these patients.

OUTLINE: This is a randomized, multicenter, pilot study. Patients are stratified according to participating center. Patients with low- to intermediate-risk disease are randomized to 1 of 4 treatment arms. Patients with high-risk disease are randomized to 1 of 3 treatment arms with imatinib mesylate-based regimens.

  • Arm I: Patients receive oral imatinib mesylate once daily for up to 12 months in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oral imatinib mesylate as in arm I. Patients also receive interferon alfa subcutaneously (SC) 3 times a week beginning at least 3 months after the start of imatinib mesylate.
  • Arm III: Patients receive oral imatinib mesylate as in arm I. Patients also receive cytarabine SC up to twice daily for 5 days monthly beginning at least 3 months after the start of imatinib mesylate.
  • Arm IV: After initial cytoreduction with hydroxyurea, patients receive interferon alfa SC daily with or without hydroxyurea. In the absence of a complete response after 3 months, patients may also receive low-dose cytarabine SC once daily. Treatment continues for up to 21 months.

Patients who fail interferon alfa therapy are crossed over to receive imatinib mesylate.

Patients who fail therapy with imatinib mesylate and are eligible for an allogeneic transplantation are stratified according to availability of donor (HLA-identical related vs unrelated), status, and participating center. Patients are randomized to receive an allogeneic transplantation or continue any salvage therapy.

Patients who are not eligible for allogeneic transplantation receive hydroxyurea and cytarabine or high-dose chemotherapy with autologous stem cell rescue followed by interferon- or imatinib mesylate-based therapy.

Patients over 45 years of age are further randomized to receive an age-adjusted standard conditioning regimen or reduced intensity preparative regimen (mini transplantation) prior to allogeneic transplantation.

Patients are followed every 6 months for 3 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,600 patients (400 per treatment arm) will be accrued for this study within 4-5 years.

Conditions
Leukemia
Being tested
recombinant interferon alfa, cytarabine, hydroxyurea, imatinib mesylate, allogeneic bone marrow transplantation
Keywords
chronic phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, chronic myelogenous leukemia, BCR-ABL1 positive
Medical subject headings
Leukemia, Leukemia, Myeloid, Chronic-Phase, Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • recombinant interferon alfaBiological

  • cytarabineDrug

  • hydroxyureaDrug

  • imatinib mesylateDrug

  • allogeneic bone marrow transplantationProcedure or surgery

  • autologous bone marrow transplantationProcedure or surgery

  • peripheral blood stem cell transplantationProcedure or surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival

  2. Risk group-dependent survival

  3. Progression-free survival

  4. Hematologic, cytogenetic, and molecular response rates

Secondary outcomes (2)

  1. Adverse drug effects

  2. Quality of life

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Mar 2003 (estimated)
  2. Study startJun 2002
  3. Primary completion31 Mar 2012
  4. Study completion31 Mar 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,551 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00055874
Sponsor's protocol ID
III-MK-CML-IV
Other IDs
CDR0000271424, EU-20248
Status last verified
Nov 2011
First submitted
6 Mar 2003
Last updated
3 May 2018
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 21422420

  • 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.

    PubMed 20142590

  • 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.

    PubMed 19965667

  • 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.

    PubMed 29479070

  • 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.

    PubMed 25918346

  • 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.

    PubMed 25465231

  • 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.

    PubMed 24837466

  • 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.

    PubMed 24658964

  • 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.

    PubMed 24622328

  • 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.

    PubMed 24297946

  • 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.

    PubMed 24162333

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing recombinant interferon alfa, cytarabine and hydroxyurea in people with Leukemia, run by Heidelberg University at 66 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 66 sites in Germany, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival. The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00055874, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2018.

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