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Chronic Myelogenous LeukemiaPhase 1/2NCT00384228

A Phase l/ll Study of AMN107 in Adult Patients With Glivec-intolerant CML or Relapsed-refractory Ph+ALL

A Phase 1/2 study testing Nilotinib in people with Chronic Myelogenous Leukemia and Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive), run by Novartis Pharmaceuticals at 1 site in Japan.

Completed

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

Official record
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Trial summary

This study will investigate if nilotinib provides an improved safety and efficacy profile over that seen in patients receiving Imatinib. Read more about this study

Who is it for?
Ages 20 years and older
What is being tested?
Nilotinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteJapan
Study dates
May 2005to Jan 2007
Phase
Phase 1/2
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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosed as Ph+ ALL who are either relapsed after or refractory to standard therapy
  • Diagnosed as CML in blast crisis or accelerated phase or chronic phase who are resistant or intolerant to imatinib
  • Performance status is normal or ambulatory and capable of all self-care Exclusion Criteria
  • A history of significant or serious uncontrolled cardiovascular disease
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of nilotinib
  • Patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control

Who cannot join

  • Cytopathologically confirmed CNS infiltration NB: in absence of suspicion of CNS involvement, lumbar puncture is not required
  • Impaired cardiac function, including any one of the following
  • LVEF < 45% as determined by echocardiogram
  • Complete left bundle branch block
  • Use of a cardiac pacemaker
  • ST depression of > 1mm in 2 or more leads and/or T-wave inversions in 2 or more contiguous leads
Show all 31Show fewer
  • Congenital long QT syndrome
  • History of or presence of significant ventricular or atrial tachyarrhythmias
  • Clinically significant resting bradycardia (< 50 beats per minute)
  • QTc > 480 msec on screening ECG (using the QTcF formula)
  • Right bundle branch block plus left anterior hemiblock, bifascicular block
  • Myocardial infarction within 3 months prior to starting AMN107
  • Uncontrolled angina pectoris
  • Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of AMN107 (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • Use of therapeutic warfarin
  • Acute or chronic liver or renal disease considered unrelated to tumor (e.g., hepatitis, cirrhosis, renal insufficiency, etc.)
  • Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
  • Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF) ≤ 1 week prior to starting study drug.
  • Patients who are currently receiving treatment with any of the medications listed in (cf. Post-text suppl. 5) that cannot be either discontinued or switched to a different medication prior to starting study drug. The medications listed in (cf. Post-text suppl. 5) have the potential to prolong the Q-T interval.
  • Patients who have received chemotherapy ≤ 1 week or who are within 5 half-lives of their last dose chemotherapy (6 weeks for nitrosurea or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy. Hydroxyurea is permitted at the investigator's discretion prior to enrollment.
  • Patients who have received Glivec® ≤ 1 week or who have not recovered from side effects of such therapy.
  • Patients who have received immunotherapy ≤ 1 week prior to starting study drug or who have not recovered from side effects of such therapy.
  • Patients who have received any investigational drug (excluding STI571/Glivec) ≤ 4 weeks or investigational cytotoxic agent within 1 week (or who are within 5 half-lives of a previous investigational cytotoxic agent) prior to starting study drug or who have not recovered from side effects of such therapy.
  • Patients who have received wide field radiotherapy ≤ 4 week or limited field radiation for palliation ≤ 2 week prior to starting study drug or who have not recovered from side effects of such therapy.
  • 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 breast feeding, 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 AMN107). Post-menopausal 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 study and for up to 3 months following discontinuation of study drug
  • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
  • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
  • Patients unwilling or unable to comply with the protocol
  • Other protocol-defined inclusion and exclusion criteria may apply.

Trial locations and contacts

1 site in 1 country.

Japan1 site

  • Novartis Investigative Site

    Tokyo

Other trials in Japan

About this study

Official title: A Phase I/II Multicenter, Dose-escalation Study of Oral Nilotinib on a Continuous Daily Dosing Schedule in Adult Patients With Imatinib-resistant or Imatinib-intolerant CML, or Relapse/Refractory Ph+ALL

This study will investigate if nilotinib provides an improved safety and efficacy profile over that seen in patients receiving Imatinib.

Being tested
Nilotinib
Keywords
Chronic Myelogenous Leukemia, Acute Lymphoblastic Leukemia
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • NilotinibDrug

    Also called AMN107

Study groups in NCT00384228
Study groupRoleWhat they receive
NilotinibExperimentalNot described
Receives: Drug: Nilotinib

What is being measured

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

  1. Safety evaluation assessed by dose limiting toxicity within first cycle of 28 day treatment and AEs within 3 cycles

    Measured: every first 28 days

  2. Pharmacokinetic (PK) profile of single and multiple doses

    Measured: day 1 and 15 of cycle 1,day 6, 8, 10, 12, 22 and 28 of cycle 1, day 15 of cycle 2

Secondary outcomes (2)

  1. Anti-leukemic activity within 3 cycles of 28 days treatment

    Measured: Day 28 cycle 1, 2 and 3, at the time of disease progression, and at the time of study completion

  2. Bone marrow and/or blood assessments to detect the presence of Bcr-Abl transcript and mutational analysis of Bcr-Abl before, during and after therapy.

    Measured: Day 28 cycle 1, 2 and 3, at the time of disease progression, and at the time of study comp

Timeline

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

  1. First posted6 Oct 2006 (estimated)
  2. Study startMay 2005
  3. Primary completionJan 2007

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00384228
Sponsor's protocol ID
CAMN107A1101
Status last verified
Apr 2012
First submitted
5 Oct 2006
Last updated
8 Dec 2020
Results posted
No

Publications

  • Lange T, Ernst T, Gruber FX, Maier J, Cross M, Muller MC, Niederwieser D, Hochhaus A, Pfirrmann M. The quantitative level of T315I mutated BCR-ABL predicts for major molecular response to second-line nilotinib or dasatinib treatment in patients with chronic myeloid leukemia. Haematologica. 2013 May;98(5):714-7. doi: 10.3324/haematol.2012.068890. Epub 2012 Oct 12.

    PubMed 23065514

  • le Coutre P, Ottmann OG, Giles F, Kim DW, Cortes J, Gattermann N, Apperley JF, Larson RA, Abruzzese E, O'Brien SG, Kuliczkowski K, Hochhaus A, Mahon FX, Saglio G, Gobbi M, Kwong YL, Baccarani M, Hughes T, Martinelli G, Radich JP, Zheng M, Shou Y, Kantarjian H. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia. Blood. 2008 Feb 15;111(4):1834-9. doi: 10.1182/blood-2007-04-083196. Epub 2007 Nov 29.

    PubMed 18048643

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nilotinib in people with Chronic Myelogenous Leukemia and Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive), run by Novartis Pharmaceuticals at 1 site in Japan.

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 6 inclusion and 31 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: finished, as of the sponsor's last update on 8 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Safety evaluation assessed by dose limiting toxicity within first cycle of 28 day treatment and AEs within 3 cycles (time frame: every first 28 days). 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 NCT00384228, which also lists 2 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 8 Dec 2020.

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