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Accelerated Phase Chronic Myelogenous LeukemiaPhase 1/2NCT00702403

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

A Phase 1/2 study testing nilotinib, imatinib mesylate and pharmacological study in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Lymphoblastic Leukemia in Remission, run by Fred Hutchinson Cancer Center at 5 sites in United States.

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 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. Read more about this study

Who is it for?
Any age
What is being tested?
nilotinib, imatinib mesylate and pharmacological study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
5 sitesUnited States
Study dates
14 Aug 2008to 1 Dec 2013
Phase
Phase 1/2

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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

  • Stanford University Hospitals and Clinics

    Stanford, California, 94305

  • H Lee Moffitt Cancer Center and Research Institute Phase 2 Consortium

    Tampa, Florida, 33612

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

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.

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety of the administration of nilotinib between Day 81 and Day 365 after hematopoietic cell transplantation (HCT) in patients with Philadelphia chromosome positive (Ph+) leukemia.

SECONDARY OBJECTIVES:

  1. To quantify the breakpoint cluster region (BCR)/Abelson murine leukemia (ABL) transcript load after HCT during tyrosine kinase inhibitor therapy in patients with Ph+ leukemia treated sequentially with imatinib (imatinib mesylate) and nilotinib from the time of engraftment.

II. To evaluate survival at 1 year in patients with Ph+ leukemia who received sequential imatinib and nilotinib from the time of engraftment.

III. To determine if imatinib can be co-administered with nilotinib for patients with rising levels of BCR/ABL on 2 consecutive occasions after HCT.

IV. To confirm that imatinib can be delivered at an average daily dose of 400 mg at least 85% of the time in the majority of adults during the first 80 days after HCT.

  1. To determine whether nilotinib can be administered safely at a daily dose of at least 300 mg (175 mg/m^2 in children < 17 years) at least 70% of the time to patients with imatinib resistant Ph+ leukemia during the first 80 days after HCT.

VI. To determine treatment efficacy success at 1 year post-transplant as demonstrated by complete hematological remission, absence of Philadelphia chromosome, and not satisfying any of the criteria for treatment failure.

OUTLINE:

Beginning after engraftment and blood count recovery (21-28 days after allogeneic stem cell transplant), patients with imatinib-sensitive leukemia receive imatinib mesylate orally (PO) once daily (QD) until day 80 and then nilotinib PO twice daily (BID) on days 81-445. Patients with imatinib-resistant leukemia receive nilotinib PO BID beginning after engraftment and blood count recovery until day 445.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Being tested
nilotinib, imatinib mesylate, pharmacological study
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Blast Crisis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Chronic-Phase, 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 AMN 107, Tasigna

    Given PO

  • imatinib mesylateDrug

    Also called CGP 57148, Gleevec, Glivec

    Given PO

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00702403
Study groupRoleWhat they receive
Treatment (prophylactic inhibition of BCR-ABL tyrosine kinase)ExperimentalBeginning after engraftment and blood count recovery (21 to 28 days after allogeneic stem cell transplant), patients with imatinib-sensitive leukemia receive imatinib mesylate PO QD until day 80 and then nilotinib PO BID on days 81-445. Patients with imatinib-resistant leukemia receive nilotinib PO BID beginning after engraftment and blood count recovery until day 445. Treatment continues in the absence of disease progression or unacceptable toxicity.
Receives: Drug: nilotinib; Drug: imatinib mesylate; Other: pharmacological study

What is being measured

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

  1. Number of Participants With Treatment Safety Failure

    Safety and tolerability of nilotinib therapy in patients with imatinib-sensitive leukemia graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0. Treatment safety failure is defined for a patient with imatinib sensitive Ph+ leukemia as the inability to be able to deliver at least 400 milligrams per day of nilotinib in adults, and 230 milligrams/m2 per day in children, for at least 85% of the time interval between 81 and 365 days after transplant. The overall study will be considered successful if nilotinib is deliverable to more than 75% of the study participants at this minimum specified dose intensity.

    Measured: Up to 365 days post-transplant

Secondary outcomes (4)

  1. The Proportion of Patients at 1 Year With Treatment Efficacy Success

    To be considered a treatment efficacy success at 1 year posttransplant, the patient's bone marrow must demonstrate complete hematological remission, absence of Philadelphia chromosomes, and not satisfy any of the criteria for treatment failure (>/= 1% aberrantly expressing marrow blasts by multiparameter flow cytometry, >5% BCR/ABL in marrow by fluorescent in situ hybridization, or >1 log rise in peripheral blood BCR/ABL by quantitative polymerase chain reaction (PCR) since day 80).

    Measured: Up to 1 year

  2. Survival

    The proportion of study participants alive at 1, 2 and 3 years

    Measured: Up to 3 years

  3. Patients Alive With Out Relapse

    The proportion of study participants alive and without hematologic, cytogenetic or molecular evidence of BCR/ABL-positive leukemia at 1 year

    Measured: Up to 1 year

  4. Relapse

    The proportion of patients with hematologic, cytogenetic or molecular relapse of BCR/ABL-positive leukemia

    Measured: 1 and 3 years

Timeline

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

  1. First posted20 Jun 2008 (estimated)
  2. Study start14 Aug 2008
  3. Primary completionDec 2013
  4. Study completion1 Dec 2013

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00702403
Sponsor's protocol ID
2223.00
Other IDs
NCI-2010-00402, P30CA015704, P01CA018029
Status last verified
Jul 2017
First submitted
19 Jun 2008
Last updated
10 Aug 2017
Data monitoring committee
Yes
Individual data sharing
No

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