NCT00750659

Brief 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. 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)

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jul 2009

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 9, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 10, 2008

Completed
10 months until next milestone

Study Start

First participant enrolled

July 1, 2009

Completed
6.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2016

Completed
Last Updated

April 20, 2016

Status Verified

April 1, 2016

Enrollment Period

6.8 years

First QC Date

September 9, 2008

Last Update Submit

April 19, 2016

Conditions

Chronic Myeloid LeukemiaAcute Lymphoblastic LeukemiaStem Cell Transplantation

Keywords

Chronic myeloid leukemiaPh+ acute lymphoblastic leukemiastem cell transplantationnilotinib

Outcome Measures

Primary Outcomes (1)

  • Safety

    12 months

Secondary Outcomes (1)

  • response

    12 months

Study Arms (1)

1

EXPERIMENTAL

Nilotinib treatment

Drug: Nilotinib

Interventions

NilotinibDRUG

Nilotinib 400 mg po/BID until transplant. Nilotinib 200-400 mg po/BID post transplant in escalated doses.

1

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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.

You may not qualify if:

  • 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
  • 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).
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Chaim Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

Related Publications (1)

  • 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.

    PMID: 25387866DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL PositivePrecursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsMyeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Arnon Nagler, MD

    Sheba Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 9, 2008

First Posted

September 10, 2008

Study Start

July 1, 2009

Primary Completion

April 1, 2016

Study Completion

April 1, 2016

Last Updated

April 20, 2016

Record last verified: 2016-04

Locations

IL(1)