Nilotinib Pre and Post Allogeneic Stem Cell Transplantation

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT00750659
First received: September 9, 2008
Last updated: November 22, 2013
Last verified: November 2013
  Purpose

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)


Condition Intervention Phase
Chronic Myeloid Leukemia
Acute Lymphoblastic Leukemia
Stem Cell Transplantation
Drug: Nilotinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Sheba Medical Center:

Primary Outcome Measures:
  • Safety [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • response [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: July 2009
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Nilotinib treatment
Drug: Nilotinib
Nilotinib 400 mg po/BID until transplant. Nilotinib 200-400 mg po/BID post transplant in escalated doses.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with Ph+ advanced CML (>CR1) or Ph+ALL.
  2. Hematological, Cytogenetic (Ph+) and/or BCR/ABL positive documented at diagnosis of CML or Ph+ALL pre- alloSCT.
  3. Patients age 18-65 years of age.
  4. .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.
  5. 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

  6. Patient must have LVEF>45% prior entry into study.
  7. Patient must have QTc <450 msec at study entry.
  8. Lung diffusion capacity (DLCO>40% predicted)
  9. 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.
  10. Written, voluntary informed consent.

Exclusion Criteria:

  1. Patients with CML in first chronic phase
  2. Patient has received any other investigational agents within 28 days of first day of study drug dosing, unless the disease is rapidly progressing.
  3. ECOG performance status > 2
  4. 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.
  5. 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).
  6. Female patients who are pregnant or breast-feeding.
  7. Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
  8. Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
  9. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
  10. Patient had a major surgery within 2 weeks prior to study entry.
  11. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
  12. Patients with active CNS disease (patients with history of CNS disease are allowed).
  13. Patients with pleural effusion or ascites
  14. Patients with a history of pancreatitis.
  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: NCT00750659

Locations
Israel
Chaim Sheba Medical Center
Tel-Hashomer, Israel, 52621
Sponsors and Collaborators
Sheba Medical Center
Investigators
Principal Investigator: Arnon Nagler, MD Sheba Medical Center
  More Information

No publications provided

Responsible Party: Sheba Medical Center
ClinicalTrials.gov Identifier: NCT00750659     History of Changes
Other Study ID Numbers: SHEBA-08-5288-AN-CTIL
Study First Received: September 9, 2008
Last Updated: November 22, 2013
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Sheba Medical Center:
Chronic myeloid leukemia
Ph+ acute lymphoblastic leukemia
stem cell transplantation
nilotinib

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on August 19, 2014