Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Randomized ph Lll Study of Imatinib Dose Optimization vs Nilotinib in CML Patients With Suboptimal Response to Imatinib (LASOR)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00802841
First received: December 3, 2008
Last updated: October 29, 2014
Last verified: October 2014
  Purpose

There is no available data on the clinical benefit of dose escalation for patients with suboptimal response to imatinib, and patients may still improve their response with continuation of therapy at the standard dose as shown in the IRIS trial after 5 years of follow-up. However, there is no data yet regarding the potential benefit of using nilotinib in the group of patients with suboptimal response. In this study, the efficacy of nilotinib 400mg BID will be compared to imatinib 600mg QD.


Condition Intervention Phase
Chronic Myelogenous Leukemia
Drug: nilotinib
Drug: imatinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase Lll Study of Imatinib Dose Optimization Compared With Nilotinib in Patients With Chronic Myelogenous Leukemia and Suboptimal Response to Standard-dose Imatinib

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • to determine the comparative efficacy between imatinib dose escalation and nilotinib, in terms of CCyR) after 6 months of treatment, for patients with CML in chronic phase with suboptimal response to imatinib standard dose [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • to compare the rate of major molecular response (MMR) between 2 arms at 12 months [ Time Frame: 12, 18 and 24 months ] [ Designated as safety issue: No ]
    rate of MMR defined as BCR-ABL less than or equal to 0.1% on IS

  • to evaluate safety and tolerability of imatinib 600mg/daily and nilotinib 400mg twice a day [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • to evaluate the rate of CCyR at 12, 18 and 24 months on study [ Time Frame: 12, 18 and 24 months ] [ Designated as safety issue: No ]
    rate of CCyR defined as 0% Ph+ metaphases

  • time to CCyR [ Time Frame: varies ] [ Designated as safety issue: No ]
    Time to CCyR defined as time from date of randomization to date of first documented CCyR

  • duration of CCyR [ Time Frame: varies ] [ Designated as safety issue: No ]
    duration of CCyR defined as time from the date of ransomization to date of first loss of CCyR or death, whichever comes first

  • Progression-Free Survival [ Time Frame: varies ] [ Designated as safety issue: No ]
    PFS defined as the time from the date of randomization to the earliest of the dates of occurrence if any progression to accelerated phase or blast crisis, or death due to any cause

  • Event-Free Survival (EFS) [ Time Frame: varies ] [ Designated as safety issue: No ]
    EFS defined as the time from the date of randomization to the dste of the first occurrence of any of the following: loss of CHR, loss of PCyR, loss of CCyR, death on treatment, progression to accelerated phase or blast crisis, whichever is earliest

  • Overall survival (OS) [ Time Frame: varies ] [ Designated as safety issue: No ]
    OS defined as time from date of randomization to date of the death


Enrollment: 179
Study Start Date: May 2009
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nilotinib
nioltinib
Drug: nilotinib
400 mg twice a day
Other Name: Tasigna
Active Comparator: Imatinib
imatinib
Drug: imatinib
600 mg daily
Other Name: Gleevec/Glivec

Detailed Description:

The comparative efficacy between imatinib dose escalation (600 mg QD) and nilotinib (400 mg BID), in terms of CCyR after 6 months, for patients with CML in chronic phase with suboptimal response to imatinib standard dose will be determined.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Male or female ≥ 18 years old;
  2. ECOG of 0, 1, or 2;
  3. Ph+ CML in CP defined as:

    • <15% blasts in peripheral blood or bone marrow;
    • <30% blasts + promyelocytes in peripheral blood or bone marrow;
    • <20% basophils in the peripheral blood;

      •≥100x109/L (≥ 100,000/mm3) platelets;

    • no evidence of extramedullary leukemia involvement, with the exception of hepatosplenomegaly;
  4. SoR to 400 mg imatinib, defined as (min of 20 metaphases):

    • No cytogenetic response at ≥ 3 to <6 months (> 95% Ph+ metaphases);or
    • No PCyR at ≥ 6 to <12 months (36 to 95% Ph+ metaphases on bone marrow); or
    • No CCyR at ≥ 12 to <18 months (1 to 35% Ph+ metaphases on bone marrow); Confirmation of SoR by FISH is allowed if BMK is done outside the screening window up to 4 wks.
  5. 400mg/daily imatinib (no higher doses) for at least 3months but no longer than 18 months;
  6. Previous use of IFN, taken prior to imatinib treatment, is allowed at a maximum of 90 days unless reason for switch from IFN to imatinib was intolerance.
  7. Parameters must be present:

    • Creatinine <2.0 X ULN
    • Total bilirubin <1.5 X ULN (< 3.0 X ULN if related to disease);
    • SGOT and SGPT < 2.5 X ULN;
    • Serum lipase ≤1.5 X ULN;
    • Alkaline phosphatase ≤2.5 X ULN
    • Serum potassium, phosphorus, magnesium and calcium ≥ LLN or corrected to WNL with supplements prior to first dose of study drug;
  8. Written informed consent prior to any study procedures being performed.

Exclusion criteria:

  1. Prior accelerated phase including clonal evolution or blast crisis CML;
  2. Prior therapy with imatinib in combination with any other CML drug other than Hydroxyurea and/or Anagrelide;

4.Imatinib therapy started more than 12 months after the date of the original diagnosis; 5.Unable to tolerate imatinib at 400mg; 6.Previous treatment with any other tyrosine kinase inhibitor except Glivec and/or CML therapy other than IFN, hydroxyurea, and /or anagrelide; 7.Myelotoxicity ≥ Grade 2 present at the time of randomization, 8.Previously documented T315I mutations; 9.Impaired cardiac function including one of these:

  • Long QT syndrome or family history of long QT syndrome
  • Clinically significant resting brachycardia (<50 bpm)
  • QTcF >450 msec on screening ECG (using the QTcF formula). If QTc >450 and electrolytes are not with normal ranges, electrolytes should be corrected and then the patient rescreened for QTc to certify QTc <450 msec;
  • Myocardial infarction ≤ 12 months prior to the first dose of study drug;
  • Other clinically significant heart disease (e.g., CHF, uncontrolled hypertension, unstable angina, significant ventricular or atrial tachyarrhythmias) 10. Impairment of GI function or disease that may significantly alter the absorption of study drug; 11. Treated with strong CYP3A4 inhibitors that cannot be either discontinued or switched to a different medication prior to starting study drug; 12.Currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug; 13.History of previous acute pancreatitis within one year of study entry or medical history of chronic pancreatitis; 14.Known cytopathologically confirmed CNS 15.Women who are pregnant, breast feeding or of a childbearing potential without a negative urine pregnancy test at screening. Female patients of childbearing potential unwilling to use effective contraceptive precautions throughout the trial and for 3 months post trial end. Post-menopausal women must be ammenorrheic for at least 12 months to be considered of non-childbearing potential; 16. History of another primary malignancy that is currently clinically significant or currently requires active intervention; 17.Any other clinically significant medical or surgical condition which, according to investigators' discretion, should preclude participation; 18.Use of investigational agent within 28 days prior to enrollment; 19.Patients unwilling or unable to comply with the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00802841

  Show 57 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00802841     History of Changes
Other Study ID Numbers: CAMN107A2404, 2008-007054-35
Study First Received: December 3, 2008
Last Updated: October 29, 2014
Health Authority: United States: Food and Drug Administration
Brazil: Ministry of Health
Mexico: Federal Commission for Protection Against Health Risks
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Panama: Ministry of Health
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Venezuela : Ministerio del Poder Popular para la Salud
Germany: Federal Institute for Drugs and Medical Devices
Poland: Ministry of Health
Guatemala: Departamento de Regulación de Productos Farmaceuticos y afines
Peru: Instituto Nacional de Salud (INS)
Russia: Federal Health Ministry
China: Ministry of Health of The People's Republic of China
India: Drugs Controller General India

Keywords provided by Novartis:
Chronic
Myelogenous
Leukemia
CML
Chronic Phase
Suboptimal Response

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Imatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014