Nilotinib and Imatinib Mesylate After Donor Stem Cell Transplant in Treating Patients With ALL or CML

Not Recruiting

Trial ID: NCT00702403

Purpose

This phase I/II trial is studying the side effects and best way to give nilotinib when given alone or sequentially after imatinib mesylate after donor stem cell transplant in treating patients with acute lymphoblastic leukemia or chronic myelogenous leukemia. Nilotinib and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Official Title

A Multicenter Phase I/II Study of the Prophylactic Inhibition of BCR-ABL Tyrosine Kinase by Tasigna ® (Nilotinib) After Hematopoietic Cell Transplantation for Philadelphia Chromosome-Positive Leukemias.

Stanford Investigator(s)

Wen-Kai Weng, MD, PhD
Wen-Kai Weng, MD, PhD

Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy) and, by courtesy, of Dermatology

Robert Lowsky
Robert Lowsky

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Laura Johnston
Laura Johnston

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Robert Negrin
Robert Negrin

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Sally Arai
Sally Arai

Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Judith Shizuru
Judith Shizuru

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy) and of Pediatrics (Stem Cell Transplantation)

Eligibility


Inclusion Criteria:

   - Body surface area >= 1 m^2

   - Allogeneic HCT

   - Acute lymphocytic leukemia (ALL) or chronic myelogenous leukemia (CML) characterized
   by the p190 and/or p210 BCR/ABL gene rearrangement

   - CML in accelerated phase, blast crisis, or blast crisis remission as defined by World
   Health Organization (WHO) criteria

   - CML in chronic phase if patient age =< 17 years or a patient of any age with CML in
   second chronic phase or beyond

   - Patients with minimal residual disease (MRD) that is not declining in response to
   tyrosine kinase inhibitor therapy must be screened for the T315I and other mutations

   - An appropriately matched related or unrelated donor

   - Signed informed consent

   - Patient must have a life expectancy of at least 2 months

   - Stated willingness of the patient to comply with study procedures and reporting
   requirements

   - Creatinine =< 2.0 x upper limit normal (ULN)

   - Platelets > 20 x 10^9 /L

   - Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN,
   conjugated bilirubin < 3 x ULN

   - Serum potassium phosphorus, magnesium, and calcium >= lower limit normal (LLN) or
   correctable with supplements prior to first dose of study drug; calcium levels may be
   corrected for hypoalbuminemia

   - Serum amylase and lipase < 1.5 x ULN

   - 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

   - Careful rationalization with a view to discontinuing or considering alternatives to
   any concomitant medications that have potential to prolong the QT interval

Exclusion Criteria:

   - Autologous transplant

   - Non-myeloablative transplant

   - Patient age > 17 years with CML in first chronic phase

   - Aberrant antigen expression on marrow leukemic blasts >= 5% by multidimensional flow
   cytometric assay immediately before conditioning (CML patients in chronic phase exempt
   from flow cytometry screening)

   - Ph+ ALL without complete cytogenetic remission immediately before conditioning

   - Known T315I mutation

   - Hypersensitivity to Gleevec or Tasigna

   - Patients who are Tasigna-resistant or intolerant

   - Central nervous system (CNS) involvement with leukemia at baseline (pre-imatinib
   therapy); CML chronic phase (CP), accelerated phase (AP) patients exempt from CNS
   involvement screening

   - Female patients who are pregnant, breast-feeding, or of childbearing potential without
   a negative serum pregnancy test at screening; male or female patients of childbearing
   potential unwilling to use effective contraceptive precautions throughout the trial;
   post-menopausal women must be amenorrheic for at least 12 months to be considered of
   non-childbearing potential

   - Life expectancy severely limited by diseases other than leukemia

   - Myocardial infarction within one year prior to starting nilotinib

   - Other clinically significant heart disease (e.g. congestive heart failure,
   uncontrolled hypertension, unstable angina)

   - Absolute neutrophil count (ANC) less than 1500 per microliter at study entry despite
   the use of filgrastim (G-CSF)

   - Impaired cardiac function, including any one of the following:

      - Complete left bundle branch block or bifascicular block (right bundle branch
      block plus left anterior hemiblock) or use of ventricular-paced pacemaker

      - Congenital long QT syndrome or a family history of long QT syndrome

      - History of or presence of significant ventricular or atrial tachyarrhythmias

      - Clinically significant resting bradycardia (< 50 beats per minute)

   - Corrected QT interval (QTc) > 450 milliseconds on screening electrocardiogram (ECG);
   if QTc > 450 and electrolytes are not within normal ranges, electrolytes should be
   corrected and then the patient rescreened for QTc

Intervention(s):

other: pharmacological study

drug: imatinib mesylate

drug: nilotinib

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Physician Referrals
6507230822

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