Comparing Imatinib Standard Dose With Imatinib High Dose Induction in Pretreated Chronic Myeloid Leukemia (CML) Patients in Chronic Phase

NCT00327262 | Unknown Phase 3

• 1 other identifier: CSTI571AAT06
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the efficacy and tolerability of a short (6 months) high dose therapy followed by a standard dose compared to a continuous treatment with a standard dose of imatinib (Glivec®) in pretreated Philadelphia chromosome- positive (Ph+)/BCR-ABL+ CML patients in chronic phase.

Conditions

Chronic Myeloid Leukemia

Keywords

chronic myeloid leukemia; Ph+; bcr/abl+; imatinib

Outcome Measures

Primary Outcomes (1)

• To determine the efficacy regarding major cytogenetic response within 12 months after randomization

Secondary Outcomes (5)

• To determine the major cytogenetic response after 3 months versus 6-12 months after randomization

• To determine the efficacy of the molecular response within 12 and 24 months after randomization

• To determine the time to molecular progression within 24 months

• To determine the dynamics of the molecular response within 3 and 6 months after randomization expressed as the slope decreases in BCR-ABL-transcripts

• To determine tolerability

Interventions

Imatinib DRUG

Eligibility Criteria

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

You may qualify if:

• Patients \> 18 years of age
• BCR-ABL positive CML patients in chronic phase, confirmed by karyotype (Ph+) or RT-PCR.
• Patients pretreated with any drug that is known to control the disease of CML in chronic phase except imatinib (Glivec®).
• Patients without a major cytogenetic response at study entry (\> 35% Ph+ metaphases in bone marrow cytogenetic analysis performed \< 3 months before study entry).
• Patients either intolerant to interferon-alpha (non-hematologic toxicity grade 3-4 for more than 2 weeks) or having received pretreatment for CML at least 12 months before study entry.
• World Health Organization (WHO) status 0-2
• Adequate end organ function, defined as the following:
• total bilirubin \< 1.5 x upper limit of normal (ULN)
• SGOT and SGPT \< 2.5 x ULN
• creatinine \< 1.5 x ULN
• absolute neutrophil count (ANC) \> 1.5 x 10 \^ 9/L
• platelets \> 100 x 10 \^ 9/L
• Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
• Written voluntary informed consent.

You may not qualify if:

• Patients eligible for allogeneic bone marrow transplantation.
• Patients in accelerated phase or blast crisis.
• Known tuberculosis or other uncontrolled infection.
• Other primary tumor of a different histological origin than the study indication (unless the relapse-free interval is \> 5 years, and with the exception of cervical carcinoma in situ \[CIS\], basal cell epithelioma, or squamous cell carcinoma of the skin).
• Major surgery within the last 14 days.
• Known to be HIV positive.
• Unstable medical disorder (except for indication) that excludes the patient in the opinion of the investigator.
• Patient has received any other investigational agents within 28 days of first day of study drug dosing.
• Patients with a WHO performance status score \> 3
• Patients with Grade III/IV cardiac problems as defined by the New York Heart Association criteria (i.e., congestive heart failure, myocardial infarction within 6 months of study).
• Female patients who are pregnant or breast-feeding.
• Refusal by female patients of childbearing age to use a safe contraceptive.
• Patients with known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
• Patients with any significant history of non-compliance to medical regimens or an inability to grant reliable informed consent.

Sponsors & Collaborators

• Central European Leukemia Study Group: lead

Study Sites (1)

Medical University Innsbruck

Innsbruck, Tyrol, 6020, Austria

RECRUITING

Related Publications (10)

• Talpaz M. Interferon-alfa-based treatment of chronic myeloid leukemia and implications of signal transduction inhibition. Semin Hematol. 2001 Jul;38(3 Suppl 8):22-7. doi: 10.1016/s0037-1963(01)90114-3.

  PMID: 11526598 BACKGROUND

• 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. doi: 10.1056/NEJMoa022457.

  PMID: 12637609 BACKGROUND

• Kantarjian H, Talpaz M, O'Brien S, Garcia-Manero G, Verstovsek S, Giles F, Rios MB, Shan J, Letvak L, Thomas D, Faderl S, Ferrajoli A, Cortes J. High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. Blood. 2004 Apr 15;103(8):2873-8. doi: 10.1182/blood-2003-11-3800. Epub 2003 Dec 24.

  PMID: 15070658 BACKGROUND

• Cortes J, Giles F, O'Brien S, Thomas D, Garcia-Manero G, Rios MB, Faderl S, Verstovsek S, Ferrajoli A, Freireich EJ, Talpaz M, Kantarjian H. Result of high-dose imatinib mesylate in patients with Philadelphia chromosome-positive chronic myeloid leukemia after failure of interferon-alpha. Blood. 2003 Jul 1;102(1):83-6. doi: 10.1182/blood-2003-01-0025. Epub 2003 Mar 13.

  PMID: 12637317 BACKGROUND

• Sawyers CL, Hochhaus A, Feldman E, Goldman JM, Miller CB, Ottmann OG, Schiffer CA, Talpaz M, Guilhot F, Deininger MW, Fischer T, O'Brien SG, Stone RM, Gambacorti-Passerini CB, Russell NH, Reiffers JJ, Shea TC, Chapuis B, Coutre S, Tura S, Morra E, Larson RA, Saven A, Peschel C, Gratwohl A, Mandelli F, Ben-Am M, Gathmann I, Capdeville R, Paquette RL, Druker BJ. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood. 2002 May 15;99(10):3530-9. doi: 10.1182/blood.v99.10.3530.

  PMID: 11986204 BACKGROUND

• Talpaz M, Silver RT, Druker BJ, Goldman JM, Gambacorti-Passerini C, Guilhot F, Schiffer CA, Fischer T, Deininger MW, Lennard AL, Hochhaus A, Ottmann OG, Gratwohl A, Baccarani M, Stone R, Tura S, Mahon FX, Fernandes-Reese S, Gathmann I, Capdeville R, Kantarjian HM, Sawyers CL. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002 Mar 15;99(6):1928-37. doi: 10.1182/blood.v99.6.1928.

  PMID: 11877262 BACKGROUND

• 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. doi: 10.1056/NEJMoa011573.

  PMID: 11870241 BACKGROUND

• Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, Capdeville R, Talpaz M. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. 2001 Apr 5;344(14):1038-42. doi: 10.1056/NEJM200104053441402.

  PMID: 11287973 BACKGROUND

• Petzer AL, Fong D, Lion T, Dyagil I, Masliak Z, Bogdanovic A, Griskevicius L, Lejniece S, Goranov S, Gercheva L, Stojanovic A, Peytchev D, Tzvetkov N, Griniute R, Stanchev A, Grubinger T, Kwakkelstein M, Schuld P, Gastl G, Wolf D. High-dose imatinib induction followed by standard-dose maintenance in pre-treated chronic phase chronic myeloid leukemia patients--final analysis of a randomized, multicenter, phase III trial. Haematologica. 2012 Oct;97(10):1562-9. doi: 10.3324/haematol.2011.060087. Epub 2012 Apr 17.

  PMID: 22511495 DERIVED

• Petzer AL, Wolf D, Fong D, Lion T, Dyagil I, Masliak Z, Bogdanovic A, Griskevicius L, Lejniece S, Goranov S, Gercheva L, Stojanovic A, Peytchev D, Tzvetkov N, Griniute R, Oucheva R, Ulmer H, Kwakkelstein M, Rancati F, Gastl G. High-dose imatinib improves cytogenetic and molecular remissions in patients with pretreated Philadelphia-positive, BCR-ABL-positive chronic phase chronic myeloid leukemia: first results from the randomized CELSG phase III CML 11 "ISTAHIT" study. Haematologica. 2010 Jun;95(6):908-13. doi: 10.3324/haematol.2009.013979. Epub 2010 Feb 9.

  PMID: 20145273 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Guenther Gastl, MD

  Medical University Innsbruck

  STUDY CHAIR

Central Study Contacts

Guenther Gastl, MD

CONTACT

++43 512 504 24003; guenther.gastl@uibk.ac.at

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 16, 2006
• First Posted: May 18, 2006
• Study Start: January 1, 2004
• Study Completion: December 1, 2008
• Last Updated: June 20, 2006

Record last verified: 2005-09

Locations

AU (1)