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CompletedNCT00702403Updated Aug 10, 2017Results posted

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

A Phase 1/2 interventional study of nilotinib and imatinib mesylate in Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission and Blastic Phase Chronic Myelogenous Leukemia, sponsored by Fred Hutchinson Cancer Center. Completed at 5 sites in United States. Per ClinicalTrials.gov, last updated 2017-08-10.

Sponsored by Fred Hutchinson Cancer Center · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
40
Allocation
Not applicable
Sex
All
01

Study 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. 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:

I. 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:

I. 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.

V. 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.

02

Conditions studied

  • Accelerated Phase Chronic Myelogenous Leukemia
  • Adult Acute Lymphoblastic Leukemia in Remission
  • Blastic Phase Chronic Myelogenous Leukemia
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Childhood Chronic Myelogenous Leukemia
  • Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Chronic Phase Chronic Myelogenous Leukemia
  • Philadelphia Positive Adult Acute Lymphoblastic Leukemia
  • Philadelphia Positive Childhood Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Relapsing Chronic Myelogenous Leukemia
  • Untreated Adult Acute Lymphoblastic Leukemia
  • Untreated Childhood Acute Lymphoblastic Leukemia
03

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 40 is close to the median of 38 across 4,247 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

Fred Hutchinson Cancer Center is the lead sponsor of 537 studies on the registry; 79 are open to participants now.

Of its 57 completed or terminated interventional studies of FDA-regulated products, 45 (79%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
40 participants (actual)

Study arms

  • Experimental
    Treatment (prophylactic inhibition of BCR-ABL tyrosine kinase)

    Beginning 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.

    Drug: nilotinib · Drug: imatinib mesylate · Other: pharmacological study

Interventions

  • Drugnilotinib

    Given PO

    Also known as: AMN 107, Tasigna

  • Drugimatinib mesylate

    Given PO

    Also known as: CGP 57148, Gleevec, Glivec

  • Otherpharmacological study

    Correlative studies

    Also known as: pharmacological studies

06

What researchers measure

Primary outcomes

  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.

    Time frame: Up to 365 days post-transplant

Secondary outcomes

  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).

    Time frame: Up to 1 year

  2. Survival

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

    Time frame: 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

    Time frame: Up to 1 year

  4. Relapse

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

    Time frame: 1 and 3 years

07

Results

Posted May 15, 2017

Participant flow

From Consent to Engraftment
Participant flow — From Consent to Engraftment
MilestoneSingle Arm Nilotinib Relapse Prophylaxis
Started57
Ineligible for study drug17
Completed40
Not completed17
Withdrew: Progressive leukemia6
Withdrew: Critically ill2
Withdrew: Corrected qt interval (qtc) >450 msec2
Withdrew: Myocardial infarction1
Withdrew: Anc<1500, plts<20k or hyperbilirubinemia4
Withdrew: Miscellaneous (unanticipated) other2
From Engraftment to Study Completion
Participant flow — From Engraftment to Study Completion
MilestoneSingle Arm Nilotinib Relapse Prophylaxis
Started40
Patient drop-outs27
Completed13
Not completed27
Withdrew: Failed pre-1st dose criteria11
Withdrew: Relapse (1 central nervous system, 3 bm)4
Withdrew: Non-compliance2
Withdrew: Adenocarcinoma1
Withdrew: Liver gvhd1
Withdrew: Suicide1
Withdrew: Acute respiratory distress syndrome1
Withdrew: Dyspnea (unrelated to nilotinib)1
Withdrew: Toxicity attributed to nilotinib5

Outcome measures

PrimaryNumber 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.

Time frame:
Up to 365 days post-transplant
Reported as:
Count of participants · Participants
Number of Participants With Treatment Safety Failure
ParticipantsSingle Arm Nilotinib Relapse Prophylaxis
Number of Participants With Treatment Safety Failure13
SecondaryThe 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).

Time frame:
Up to 1 year
Reported as:
Count of participants · Participants
The Proportion of Patients at 1 Year With Treatment Efficacy Success
ParticipantsTreatment (Prophylactic Inhibition of BCR-ABL Tyrosine Kinase)
By intention to treat29
Excluding early non-relapse deaths29
SecondarySurvival

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

Time frame:
Up to 3 years
Reported as:
Count of participants · Participants
Survival
ParticipantsTreatment (Prophylactic Inhibition of BCR-ABL Tyrosine Kinase)
Overall Survival at 1 year31
Overal Survival at 2 years28
Overall Survival at 3 years28
SecondaryPatients 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

Time frame:
Up to 1 year
Reported as:
Count of participants · Participants
Patients Alive With Out Relapse
ParticipantsSingle Arm Nilotinib Relapse Prophylaxis
Patients Alive With Out Relapse29
SecondaryRelapse

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

Time frame:
1 and 3 years
Reported as:
Count of participants · Participants
Relapse
ParticipantsTreatment (Prophylactic Inhibition of BCR-ABL Tyrosine Kinase)
Proportion with relapse at 1 year5
Proportion with relapse at 3 years6

Adverse events

Collected over Adverse Events: Conditioning through Day 100; Severe Adverse Events Conditioning >Day 100. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Single Arm Nilotinib Relapse Prophylaxis9/40 (22.5%)20/40 (50%)31/40 (77.5%)
Most frequent serious events
Showing 10 of 46
Most frequent serious events
EventSingle Arm Nilotinib Relapse Prophylaxis
NauseaGastrointestinal disorders3/40
Fever/URIInfections and infestations2/40
DiarrheaGastrointestinal disorders2/40
VomitingGastrointestinal disorders2/40
Respiratory FailureRespiratory, thoracic and mediastinal disorders2/40
Acute acalculous cholecystitisHepatobiliary disorders1/40
Hepatic FailureHepatobiliary disorders1/40
TransaminitisHepatobiliary disorders1/40
Pseudomonas bacteremiaInfections and infestations1/40
Gram negative rod bacteremia with possible urosepsisInfections and infestations1/40
Most frequent other events
Showing 10 of 45
Most frequent other events
EventSingle Arm Nilotinib Relapse Prophylaxis
ThrombocytopeniaBlood and lymphatic system disorders19/40
LymphocytopeniaBlood and lymphatic system disorders11/40
Elevated Serum AST/ALTMetabolism and nutrition disorders10/40
CMV ReactivationInfections and infestations7/40
AnemiaBlood and lymphatic system disorders7/40
NeutropeniaBlood and lymphatic system disorders7/40
LeukopeniaBlood and lymphatic system disorders6/40
Coagulase-negative staphInfections and infestations3/40
BK VirusInfections and infestations2/40
CytopeniaBlood and lymphatic system disorders2/40

Baseline characteristics

Age, Continuous
Age, Continuous(years)Single Arm Nilotinib Relapse Prophylaxis
Median42.5 (11 to 65)
Sex: Female, Male
Sex: Female, Male(Participants)Single Arm Nilotinib Relapse Prophylaxis
Female15
Male25
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Single Arm Nilotinib Relapse Prophylaxis
Hispanic or Latino4
Not Hispanic or Latino36
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Single Arm Nilotinib Relapse Prophylaxis
American Indian or Alaska Native3
Asian1
Native Hawaiian or Other Pacific Islander1
Black or African American0
White33
More than one race1
Unknown or Not Reported1
Region of Enrollment
Region of Enrollment(participants)Single Arm Nilotinib Relapse Prophylaxis
United States40
08

Study locations

5 sites
  • Stanford University Hospitals and Clinics
    Stanford, California 94305, United States
  • H Lee Moffitt Cancer Center and Research Institute Phase 2 Consortium
    Tampa, Florida 33612, United States
  • H. Lee Moffitt Cancer Center and Research Institute
    Tampa, Florida 33612, United States
  • Oregon Health and Science University
    Portland, Oregon 97239, United States
  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    Seattle, Washington 98109, United States
09

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 10, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00702403
Lead sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
Responsible party
Paul Carpenter (Principal Investigator, Fred Hutchinson Cancer Center) — Principal investigator
First posted
Jun 20, 2008
Start date
Aug 14, 2008
Primary completion
Dec 2013
Completion
Dec 1, 2013
Results posted
May 15, 2017
Last update
Aug 10, 2017

Study contacts

Paul Carpenter
principal investigator · Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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