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Chronic Myeloid Leukemia (CML)Phase 4MACS1881NCT01605981

Trial Evaluating Nilotinib as Treatment for Newly Diagnosed CML Patients in Accelerated Phase.

A Phase 4 study testing AMN107 in people with Chronic Myeloid Leukemia (CML), run by Novartis Pharmaceuticals at 18 sites in Brazil.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is an open label, non randomized, prospective, multicenter, phase II clinical trial evaluating nilotinib 400 mg BID for the treatment of newly diagnosed CML-AP patients. Patients enrolled into the study will receive 400mg of nilotinib, orally, twice daily (800mg/day) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Myeloid Leukemia (CML)
What is being tested?
AMN107
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
18 sitesBrazil
Study dates
Feb 2014to Jan 2017
Phase
Phase 4
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients age > 18 years old;
  • Diagnosis of Chronic Myeloid leukemia in Accelerated Phase (CML-AP);
  • Patients with CML-AP(See Appendix 1) within 3 months of diagnosis (date of initial diagnosis is the date of first reported cytogenetic analysis). Standard conventional cytogenetic analysis must be done on bone marrow. FISH cannot be used for purpose of inclusion;
  • Patients with atypical BCR-ABL transcripts are eligible (transcripts other then b2a2 an b3a2);
  • No previous treatment with any antileukemic drugs with the exception of hydroxyurea (HU) and/or anagrelide. In emergent cases where the patient requires disease management while awaiting study start, commercial supplies of Gleevec/Glivec at any dose may be prescribed to the patient but for no longer than 2 weeks in duration;
  • ECOG 0,1 or 2;
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  • Normal serum levels > LLN (lower limit of normal) or corrected to within normal limits with supplements, prior to the first dose of study medication, of potassium magnesium and calcium;
  • AST and ALT < 2.5 x ULN (upper limit of normal) or < 5.0 x ULN if considered due to leukemia;
  • Alkaline phosphatase < 2.5 x ULN, unless considered due to leukemia;
  • Total bilirubin < 1.5 x ULN;
  • Serum lipase and amylase < 1.5 x ULN;
  • Written informed consent prior to any study procedures being performed.

Who cannot join

  • Patients in Chronic and Blastic Phases.
  • Patients who are considered Ph negative because they do not have a confirmed cytogenetic diagnosis of Philadelphia Ph+ chromosome (9;22 translocation) in > 20 metaphases.
  • Treatment with tyrosine kinase inhibitors or other antileukemic agents or treatments (including HSCT) for longer than 2 weeks, with the exception of HU and/or anagrelide
  • Previously documented T315I mutations;
  • Uncontrolled congestive heart failure or hypertension;
  • Myocardial infarction or unstable angina pectoris within past 12 months;
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  • Significant arrhythmias, including history or presence of clinically significant ventricular or atrial tachyarrhythmias, clinically significant bradycardias, long QT syndrome and/or QTc > 450 msec on screening ECG (using the QTcF formula). Patients with complete LBBB;
  • History of confirmed acute or chronic pancreatitis;
  • Other concurrent uncontrolled medical conditions (e.g. uncontrolled diabetes, active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol;
  • Impaired gastrointestinal function or GI disease that may alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery);
  • Patients with another primary malignancy that is currently clinically significant or requires active intervention;
  • Concomitant medications with potential QT prolongation (See link for complete list: http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm);
  • Concomitant medications known to interact with CYP450 isoenzymes (CYP 3A4, CYP2C9, CYP2C8, (See link for complete list (http://medicine.iupui.edu/flockhart/table.htm);
  • History of significant congenital or acquired bleeding disorder unrelated to cancer;
  • Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy;
  • Patients who are pregnant or breastfeeding or adults of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of nilotinib). Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the entire study and up to 3 months following discontinuation of study drug;
  • Treatment with any hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF) 1 week prior to starting study drug;
  • Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 30 days of Day 1;
  • Patients unwilling or unable to comply with the protocol.
  • Note:
  • Patients who did not meet one or more inclusion or exclusion criteria may be re-screened for this study at a later time if the medical condition is transient and has been appropriately treated (provided they enter the study within 3 months of diagnosis). Date of diagnosis is defined as date of confirmatory bone marrow cytogenetic analysis.

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

Brazil18 sites

  • Novartis Investigative Site

    Belo Horizonte, Minas Gerais, 30130-100

  • Novartis Investigative Site

    Campinas, São Paulo, 13083-970

  • Novartis Investigative Site

    Cuiaba, Mato Grosso do Sul, 033426-102

  • Novartis Investigative Site

    Curitiba, Paraná, 80060-900

  • Novartis Investigative Site

    Florianópolis, Santa Catarina, 88034-000

  • Novartis Investigative Site

    Fortaleza, Ceará, 60115-290

  • Novartis Investigative Site

    Goiânia, Goiás, 74605-020

  • Novartis Investigative Site

    Jaú, São Paulo, 17210-080

  • Novartis Investigative Site

    Niterói, Rio de Janeiro, 24030210

  • Novartis Investigative Site

    Porto Alegre, Porto Alegre-RS

  • Novartis Investigative Site

    Porto Alegre, Rio Grande do Sul, 90035-903

  • Novartis Investigative Site

    Rio de Janeiro, Rio de Janeiro, 20.211-030

  • Novartis Investigative Site

    Santo André, São Paulo, 09190-615

  • Novartis Investigative Site

    Santos, São Paulo, 11075-350

  • Novartis Investigative Site

    São José, São Paulo, 15015-110

  • Novartis Investigative Site

    São Paulo, São Paulo, 05651-901

  • Novartis Investigative Site

    São Paulo, São Paulo, 08270-070

  • Novartis Investigative Site

    São Paulo, 03454-000

Other trials in Brazil

About this study

Official title: A Phase II, Non Randomized, Open Label, Trial Evaluating Nilotinib as Treatment for Newly Diagnosed CML Patients in Accelerated Phase.

This is an open label, non randomized, prospective, multicenter, phase II clinical trial evaluating nilotinib 400 mg BID for the treatment of newly diagnosed CML-AP patients.

Patients enrolled into the study will receive 400mg of nilotinib, orally, twice daily (800mg/day)

Read the detailed description

Patients will be evaluated for safety throughout the study and for response every month for the first 3 months, then every 3 months thereafter up to month 24.

BCR-ABL transcripts measurement by QRT-PCR and mutation analyses will be done on peripheral blood samples and cytogenetic analyses on bone marrow aspirates.

Laboratory tests (hematology, blood chemistry), ECG and physical examination will be done on every visit.

Drug pharmacokinetics will be assessed in this study. For the screening Baseline periods, see chart attached

Being tested
AMN107
Keywords
Nilotinib, CML patients, accelerated phase
Medical subject headings
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.

  • AMN107Drug

Study groups in NCT01605981
Study groupRoleWhat they receive
Nilotinib oralExperimentalNilotinib oral dose of 400 mg BID (800 mg/day) continuous dosing for up to 24 months. Nilotinib oral dose of 300 mg BID (600 mg/day) continuous dosing in case of intolerance. Nilotinib oral dose of 400 mg QD (400 mg/day) continuous dosing in case of intolerance
Receives: Drug: AMN107

What is being measured

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

  1. To evaluate the safety and tolerability profile of nilotinib in newly diagnosed CML-AP

    The toxicity criteria will be evaluated according to National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 3.0.

    Measured: 12 month

  2. To test the efficacy of nilotinib 400 mg BID

    To test the efficacy of nilotinib 400 mg BID in inducing complete cytogenetic response (CCyR) at 12 months in newly diagnosed CML-AP patients

    Measured: 12 months

Secondary outcomes (5)

  1. Evaluate the rate of complete hematologic response (CHR)

    Evaluate the rate of complete hematologic response (CHR) with nilotinib 400 mg BID at 3 months.

    Measured: 3 months

  2. Evaluate the Quality of Life

    Evaluate the Quality of Life by FACT-Leu Version 4 questionnaire at 3, 6, 9, 12, 15, 18 and 24 months.

    Measured: 3, 6, 9, 12, 15, 18 and 24 months

  3. Evaluate the median time to achieve molecular response

    Evaluate the median time to achieve molecular response and the cumulative probability of obtaining molecular response during the first 2 years of treatment. This will be undertaken through the analysis of the best molecular response at 3, 6, 12, 18 and 24 months. MMR will be preferred and it will be defined as a BCR-ABL/ABL ratio ≤ 0.1% IS using RQ-PCR, but any log reduction between 1 and 4,5 logs will be considered a molecular response.

    Measured: uring the first 2 years of treatment

  4. Evaluate the proportion of patients achieving CCyR

    Evaluate the proportion of patients achieving CCyR at 3, 6, 12, 18 and 24 months or undetectable BCR-ABL levels at 12, 18 and 24 months as well as the duration of sustained response.

    Measured: 3, 6, 12, 18 and 24 months or undetectable BCR-ABL levels at 12, 18 and 24 months

  5. To correlate the probability of reaching MMR, CMR and CCyR

    To correlate the probability of reaching MMR, CMR and CCyR with the risk of progression to blastic phase, relapse and overall survival.

    Measured: 2 years

Timeline

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

  1. First posted25 May 2012 (estimated)
  2. Study startFeb 2014
  3. Primary completionJan 2017 (estimated)
  4. Study completionJan 2017 (estimated)

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 4
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01605981
Sponsor's protocol ID
CAMN107EBR06
Acronym
MACS1881
Status last verified
Jun 2014
First submitted
23 May 2012
Last updated
20 Apr 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing AMN107 in people with Chronic Myeloid Leukemia (CML), run by Novartis Pharmaceuticals at 18 sites in Brazil.

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

Who may be eligible to take part?

The sponsor lists 12 inclusion and 21 exclusion criteria. 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: withdrawn, as of the sponsor's last update on 20 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Brazil. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 was withdrawn before enrolling participants, so there are no results.

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?

To evaluate the safety and tolerability profile of nilotinib in newly diagnosed CML-AP (time frame: 12 month). The study lists 2 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 NCT01605981.

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 20 Apr 2017.

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