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Glivec® (Imatinib Mesylate, STI571) in Monotherapy Versus Glivec®-Interferon Alpha in the Treatment of Chronic-Phase Chronic Myeloid Leukaemia
This study has been completed.
First Received: October 20, 2006   Last Updated: November 26, 2008   History of Changes
Sponsored by: PETHEMA Foundation
Information provided by: PETHEMA Foundation
ClinicalTrials.gov Identifier: NCT00390897
  Purpose

To compare the complete cytogenetic response rate in patients with newly-diagnosed chronic-phase chronic myeloid leukaemia treated with Glivec® alone or in combination with interferon at low doses


Condition Intervention Phase
Chronic Myeloid Leukaemia
Drug: Glivec
Drug: Interferon
Phase IV

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic
Drug Information available for: Interferon alfa-2a Imatinib Imatinib mesylate Interferon alfa-n1 Interferons
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title: Randomised Multicentre Phase IV Study to Compare Glivec® (Imatinib Mesylate, STI571) in Monotherapy Versus Glivec® in Combination With Interferon Alpha at Low Doses in the Treatment of Newly-Diagnosed Chronic-Phase Chronic Myeloid Leukaemia

Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • The fundamental objective of this study is to compare the therapeutic efficacy of Glivec® given in monotherapy (providing for dose scaling according to the response obtained at different periods of time from the beginning) in combination with standard in
  • The median survival of patients with CML is close to 7 years.
  • One year and a half after diagnosis, the rate of progression to the acceleration phase and blastic crisis is very low (3.3%) in patients treated with Glivec® as first line.
  • With the treatments available hitherto, the achievement of a major cytogenetic response and above all cytogenetic response translates into a prolongation of survival.
  • Therefore, taking into account that the rate of complete cytogenetic responses to Glivec® in newly-diagnosed CML is 76% after 18 months of treatment (see table I), the fundamental objective of the study will be to compare the rate of complete cytogenetic

Secondary Outcome Measures:
  • The time until complete cytogenetic responses are obtained
  • Rate of major cytogenetic responses
  • Rate of molecular responses
  • Time to the loss of cytogenetic, haematological or molecular response
  • Time to the progression of the disease to the phases of acceleration and blastic crisis (analysed according to intention to treat)
  • Survival (analysed according to intention to treat)
  • Haematological and non haematological tolerance and safety

Estimated Enrollment: 360
Study Start Date: July 2003
Study Completion Date: December 2007
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Detailed Description:

Open, prospective, multicentre, phase IV, comparative and randomised study

  Eligibility

Ages Eligible for Study:   18 Years to 72 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with newly-diagnosed chronic-phase Ph-positive chronic myeloid leukaemia (maximum 3 months as of the diagnosis of the disease, with the date of the cytogenetic study regarded as such).
  2. Age between 18 and 72 years (both included).
  3. Performance status < 2 on the ECOG scale (see Annex 3).
  4. Secure written or oral informed consent in the presence of a witness and consent for biological samples (annexes 5 and 6).

Exclusion Criteria:

  1. Criteria of acceleration or blastic crisis (see Annex 7).
  2. When there is a compatible family donor in patients aged under 40 years or a non-relative donor in patients aged under 30 years (in whom allogenic transplant is still regarded as first-line treatment), the possibility of performing an allogenic transplant as first therapeutic option should be considered. In any case, as this aspect is still a matter of debate, it is left up to each group to take the relevant decision depending on the institution's policy.
  3. Administration of other treatments before inclusion in the protocol (a maximum of 3 months of monotherapy with hydroxyurea is permitted).
  4. Altered hepatic or renal function (SGOT, SGPT, total bilirubin and creatinine > 1.5 times the upper limit of normality).
  5. Uncontrolled diseases, such as thyroidal dysfunction, diabetes mellitus, angina pectoralis, serious heart failure (functional class III/IV of the New York Heart Association classification), neuropsychiatric infection or disease (see annex 15).
  6. Positive serology for HIV.
  7. Record of cancer in the last 5 years (barring basal cell skin carcinoma and cervical carcinoma in situ).
  8. Pregnancy or breastfeeding
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00390897

  Show 51 Study Locations
Sponsors and Collaborators
PETHEMA Foundation
Investigators
Study Chair: Cervantes Francisco, Dr Hospital Clínic Barcelona
  More Information

Additional Information:
Publications:
RUDKIN CT, HUNGERFORD DA, NOWELL PC. DNA CONTENTS OF CHROMOSOME PH1 AND CHROMOSOME 21 IN HUMAN CHRONIC GRANULOCYTIC LEUKEMIA. Science. 1964 Jun 5;144:1229-31. No abstract available.
Rowley JD. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature. 1973 Jun 1;243(5405):290-3. No abstract available.
Heisterkamp N, Jenster G, ten Hoeve J, Zovich D, Pattengale PK, Groffen J. Acute leukaemia in bcr/abl transgenic mice. Nature. 1990 Mar 15;344(6263):251-3.
Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science. 1990 Feb 16;247(4944):824-30.
Goldman JM, Szydlo R, Horowitz MM, Gale RP, Ash RC, Atkinson K, Dicke KA, Gluckman E, Herzig RH, Marmont A, et al. Choice of pretransplant treatment and timing of transplants for chronic myelogenous leukemia in chronic phase. Blood. 1993 Oct 1;82(7):2235-8.
[No authors listed] Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. The Italian Cooperative Study Group on Chronic Myeloid Leukemia. N Engl J Med. 1994 Mar 24;330(12):820-5.
Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001 Apr 5;344(14):1031-7.
Savage DG, Antman KH. Imatinib mesylate--a new oral targeted therapy. N Engl J Med. 2002 Feb 28;346(9):683-93. Review. No abstract available.
Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C, Niederwieser D, Resta D, Capdeville R, Zoellner U, Talpaz M, Druker B, Goldman J, O'Brien SG, Russell N, Fischer T, Ottmann O, Cony-Makhoul P, Facon T, Stone R, Miller C, Tallman M, Brown R, Schuster M, Loughran T, Gratwohl A, Mandelli F, Saglio G, Lazzarino M, Russo D, Baccarani M, Morra E; International STI571 CML Study Group. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002 Feb 28;346(9):645-52. Erratum in: N Engl J Med 2002 Jun 13;346(24):1923.
O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, Lechner K, Nielsen JL, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman JM, Kantarjian H, Taylor K, Verhoef G, Bolton AE, Capdeville R, Druker BJ; IRIS Investigators. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003 Mar 13;348(11):994-1004.
Kantarjian HM, Talpaz M, O'Brien S, Giles F, Garcia-Manero G, Faderl S, Thomas D, Shan J, Rios MB, Cortes J. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood. 2003 Jan 15;101(2):473-5. Epub 2002 Sep 12.
Rea D, Legros L, Raffoux E, Thomas X, Turlure P, Maury S, Dupriez B, Pigneux A, Choufi B, Reman O, Stephane D, Royer B, Vigier M, Ojeda-Uribe M, Recher C, Dombret H, Huguet F, Rousselot P; Intergroupe Francais des Leucemies Myeloides Chronique; Group for Research in Adult Acute Lymphoblastic Leukemia. High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia. Leukemia. 2006 Mar;20(3):400-3.
Deng M, Daley GQ. Expression of interferon consensus sequence binding protein induces potent immunity against BCR/ABL-induced leukemia. Blood. 2001 Jun 1;97(11):3491-7.
Bhatia R, Wayner EA, McGlave PB, Verfaillie CM. Interferon-alpha restores normal adhesion of chronic myelogenous leukemia hematopoietic progenitors to bone marrow stroma by correcting impaired beta 1 integrin receptor function. J Clin Invest. 1994 Jul;94(1):384-91.
Bhatia R, Wayner EA, McGlave PB, Verfaillie CM. Interferon-alpha restores normal adhesion of chronic myelogenous leukemia hematopoietic progenitors to bone marrow stroma by correcting impaired beta 1 integrin receptor function. J Clin Invest. 1994 Jul;94(1):384-91.
Thiesing JT, Ohno-Jones S, Kolibaba KS, Druker BJ. Efficacy of STI571, an abl tyrosine kinase inhibitor, in conjunction with other antileukemic agents against bcr-abl-positive cells. Blood. 2000 Nov 1;96(9):3195-9.
Kano Y, Akutsu M, Tsunoda S, Mano H, Sato Y, Honma Y, Furukawa Y. In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents. Blood. 2001 Apr 1;97(7):1999-2007.
Kano Y, Akutsu M, Tsunoda S, Mano H, Sato Y, Honma Y, Furukawa Y. In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents. Blood. 2001 Apr 1;97(7):1999-2007.
Kontsioti F, Pappa V, Papasteriadis C, Economopulos T, Dervenoulas J, Papageorgiou E, Kalantzis D, Valsami S, Pappa M, Raptis S. In vitro effect of STI-571 in combination with A-interferon of the proliferation, differentiation and apoptosis of K562 cells. Hematol J 2002; suppl 1:980.
O´Brien SG, Vallance SE, Craddock C, Holyoake TL, Goldman JM. PEGIntron and STI571 combination evaluation study (PISCES) in chronic phase chronic myeloid leukaemia. Blood 2001; suppl.:3512.
Trabacchi E, Bassi S, Saglio G, Rege-cambrin G, Bonifazi F, De Vivo A, Testoni N, Martinelli G, Ruggeri D, Amabile M, Giannini B, Alberti D, Fincato GL, Tura S, Rosti G, Baccarani M. Pegylated recombinant interferon alfa 2b (PEGIntron) associated with imatinib mesylate (Glivec) in Ph chronic myeloid leukaemia (CML) in early chronic phase: a phase II study of the ICSG on CML. Hematol J 2002, suppl. :586
O´Dwyer ME, Mauro MJ, Aust S, Kuyl J, PaquetteR, Sawyers C, Druker BJ. Ongoing evaluation of the combination of imatinib mesylate (Glivectm) with low dose interferon-alpha for the treatment of chronic phase CML. Hematol J 2002; suppl. : 990

Responsible Party: pethema ( Pethema )
Study ID Numbers: LMC/PETHEMA, 03-0289
Study First Received: October 20, 2006
Last Updated: November 26, 2008
ClinicalTrials.gov Identifier: NCT00390897     History of Changes
Health Authority: Spain: Ministry of Health

Keywords provided by PETHEMA Foundation:
chronic myeloid leukaemia
Glivec
Interferon

Study placed in the following topic categories:
Interferon-alpha
Immunologic Factors
Hematologic Diseases
Interferons
Myeloproliferative Disorders
Leukemia, Myeloid
Leukemia, Myeloid, Chronic-Phase
Protein Kinase Inhibitors
Antiviral Agents
Imatinib
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chronic Myelogenous Leukemia
Bone Marrow Diseases
Interferon Alfa-2a

Additional relevant MeSH terms:
Interferon-alpha
Anti-Infective Agents
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Hematologic Diseases
Physiological Effects of Drugs
Interferons
Myeloproliferative Disorders
Enzyme Inhibitors
Leukemia, Myeloid
Leukemia, Myeloid, Chronic-Phase
Protein Kinase Inhibitors
Antiviral Agents
Pharmacologic Actions
Imatinib
Leukemia
Neoplasms
Therapeutic Uses
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Bone Marrow Diseases

ClinicalTrials.gov processed this record on May 07, 2009