Chronic Myeloid LeukemiaPhase 2NCT00750659
Nilotinib Pre and Post Allogeneic Stem Cell Transplantation
A Phase 2 study testing Nilotinib in people with Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Sheba Medical Center at 1 site in Israel.
Trial summary
Current therapeutic results in advanced chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) are rather disappointing. Most of these patients will eventually undergo allogeneic stem cell transplantation. Nilotinib is a novel TKI tyrosine kinase inhibitor with 30 fold more potency than Imatinib. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Myeloid Leukemia, Acute Lymphoblastic Leukemia, Stem Cell Transplantation
- What is being tested?
- Nilotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteIsrael
- Study dates
- Jul 2009to Apr 2016
- Phase
- Phase 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with Ph+ advanced CML (>CR1) or Ph+ALL.
- Hematological, Cytogenetic (Ph+) and/or BCR/ABL positive documented at diagnosis of CML or Ph+ALL pre- alloSCT.
- Patients age 18-65 years of age.
- .Patients must have an HLA compatible donor willing and capable of donating peripheral blood stem cells (first choice) or bone marrow progenitor cells using conventional techniques, and blood lymphocytes if indicated (HLA compatible defined as 5/6 or 6/6 matched related or matched unrelated donor.
- Adequate end organ function, defined as the following:
- total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x UNL , creatinine < 1.5 x ULN
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- Patient must have LVEF>45% prior entry into study.
- Patient must have QTc <450 msec at study entry.
- Lung diffusion capacity (DLCO>40% predicted)
- 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.
Who cannot join
- Patients with CML in first chronic phase
- Patient has received any other investigational agents within 28 days of first day of study drug dosing, unless the disease is rapidly progressing.
- ECOG performance status > 2
- Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
- Impaired cardiac function including any one of the following:
- LVEF < 45% or below the institutional lower limit of the normal range (whichever is higher) as determined by echocardiogram
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- Inability to determine the QT interval on ECG
- Complete left bundle branch block
- Long QT syndrome or a known family history of long QT syndrome.
- Clinically significant resting bradycardia (<50 beats per minute)
- QTc > 450 msec on baseline ECG (using the QTcF formula). If QTcF >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
- Myocardial infarction within 12 months prior to starting study
- Other clinically significant heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension).
- Female patients who are pregnant or breast-feeding.
- Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
- Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
- Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
- Patient had a major surgery within 2 weeks prior to study entry.
- Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
- Patients with active CNS disease (patients with history of CNS disease are allowed).
- Patients with pleural effusion or ascites
- Patients with a history of pancreatitis.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Open-label Trial of Nilotinib in Patients With Advanced (>CP1) Chronic Myeloid Leukemia or Ph+ Acute Lymphatic Leukemia Pre- and Post- Allogeneic Stem Cell Transplantation.
Current therapeutic results in advanced chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) are rather disappointing. Most of these patients will eventually undergo allogeneic stem cell transplantation. Nilotinib is a novel TKI tyrosine kinase inhibitor with 30 fold more potency than Imatinib. Based on previous preliminary experience the author we rationalize that Nilotinib therapy pre- allogeneic transplantation for patients with advanced CML and Ph+ALL will reduce tumor mass pre- transplant achieving a state of minimal residual disease (MRD) and therefore may improve transplantation outcome without increasing toxicity. In addition it will allow time for improving patient medical condition and for finding an unrelated donor which will enable allogeneic transplantation , and to induce anti tumor effect post PBSC w\o DLI ( donor lymphocyte infusion)
- Being tested
- Nilotinib
- Keywords
- Chronic myeloid leukemia, Ph+ acute lymphoblastic leukemia, stem cell transplantation, nilotinib
- 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
Nilotinib 400 mg po/BID until transplant. Nilotinib 200-400 mg po/BID post transplant in escalated doses.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Nilotinib treatment Receives: Drug: Nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Measured: 12 months
Secondary outcomes (1)
response
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2008 (estimated)
- Study startJul 2009
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Arnon Nagler, MD, Principal investigator, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00750659
- Sponsor's protocol ID
- SHEBA-08-5288-AN-CTIL
- Status last verified
- Apr 2016
- First submitted
- 9 Sep 2008
- Last updated
- 20 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Shimoni A, Volchek Y, Koren-Michowitz M, Varda-Bloom N, Somech R, Shem-Tov N, Yerushalmi R, Nagler A. Phase 1/2 study of nilotinib prophylaxis after allogeneic stem cell transplantation in patients with advanced chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015 Mar 15;121(6):863-71. doi: 10.1002/cncr.29141. Epub 2014 Nov 11.
PubMed 25387866
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label Trial of Nilotinib in Patients With Advanced (>CP1) Chronic Myeloid Leukemia or Ph+ Acute Lymphatic Leukemia Pre- and Post- Allogeneic Stem Cell Transplantation.
- ClinicalTrials.gov ID
- NCT00750659
- Acronym / sponsor ID
- SHEBA-08-5288-AN-CTIL
- Keywords
- Chronic myeloid leukemia, Ph+ acute lymphoblastic leukemia, stem cell transplantation, nilotinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- Jul 2009
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 10 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Current therapeutic results in advanced chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) are rather disappointing. Most of these patients will eventually undergo allogeneic stem cell transplantation. Nilotinib is a novel TKI tyrosine kinase inhibitor with 30 fold more potency than Imatinib. Based on previous preliminary experience the author we rationalize that Nilotinib therapy pre- allogeneic transplantation for patients with advanced CML and Ph+ALL will reduce tumor mass pre- transplant achieving a state of minimal residual disease (MRD) and therefore may improve transplantation outcome without increasing toxicity. In addition it will allow time for improving patient medical condition and for finding an unrelated donor which will enable allogeneic transplantation , and to induce anti tumor effect post PBSC w\o DLI ( donor lymphocyte infusion)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: NilotinibNilotinib treatment |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with Ph+ advanced CML (>CR1) or Ph+ALL.
- Hematological, Cytogenetic (Ph+) and/or BCR/ABL positive documented at diagnosis of CML or Ph+ALL pre- alloSCT.
- Patients age 18-65 years of age.
- .Patients must have an HLA compatible donor willing and capable of donating peripheral blood stem cells (first choice) or bone marrow progenitor cells using conventional techniques, and blood lymphocytes if indicated (HLA compatible defined as 5/6 or 6/6 matched related or matched unrelated donor.
- Adequate end organ function, defined as the following:
Key exclusion criteria (22 listed)
- Patients with CML in first chronic phase
- Patient has received any other investigational agents within 28 days of first day of study drug dosing, unless the disease is rapidly progressing.
- ECOG performance status > 2
- Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
- Impaired cardiac function including any one of the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NilotinibNilotinib 400 mg po/BID until transplant. Nilotinib 200-400 mg po/BID post transplant in escalated doses. | Drug | 1 |
Primary outcome
Safety
Time frame: 12 months
1 secondary outcome
response
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2016.
- Derived from this study: PubMed 25387866Shimoni A, Volchek Y, Koren-Michowitz M, Varda-Bloom N, Somech R, Shem-Tov N, Yerushalmi R, Nagler A. Phase 1/2 study of nilotinib prophylaxis after allogeneic stem cell transplantation in patients with advanced chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015 Mar 15;121(6):863-71. doi: 10.1002/cncr.29141. Epub 2014 Nov 11.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arnon Nagler, MD principal investigator
Sheba Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nilotinib in people with Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Sheba Medical Center at 1 site in Israel.
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 11 inclusion and 22 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 20 Apr 2016. 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 Israel. 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 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 (time frame: 12 months). 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 NCT00750659, which also lists 1 linked publication.
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 2016; AzTrials last refreshed its copy on 1 Nov 2026.