Imatinib Mesylate and Nilotinib After Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia - Full Text View

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00702403

Purpose

RATIONALE: Imatinib mesylate and nilotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I/II trial is studying the side effects of nilotinib when given together with or without imatinib mesylate and to see how well they work when given after donor stem cell transplant in treating patients with acute lymphoblastic leukemia or chronic myelogenous leukemia.

Condition	Intervention	Phase
Leukemia	Drug: imatinib mesylate Drug: nilotinib	Phase I Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Imatinib Imatinib mesylate Tyrosine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety and tolerability [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Efficacy of treatment as demonstrated by complete hematological remission, absence of Philadelphia chromosome, and absence of treatment failure at 1 year post-transplant [ Designated as safety issue: No ]
Molecular minimal residual disease as determined by PCR analysis [ Designated as safety issue: No ]
Survival [ Designated as safety issue: No ]
Relapse [ Designated as safety issue: No ]
Relapse-free survival [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	August 2008
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Imatinib mesylate-sensitive leukemia: Experimental Patients receive oral imatinib mesylate once daily beginning on the day of engraftment (between 21 and 42 days after transplant) and continuing until day 80. Patients then receive oral nilotinib twice daily on days 81-445 in the absence of disease progression or unacceptable toxicity.	Drug: imatinib mesylate Given orally Drug: nilotinib Given orally
Imatinib mesylate-resistant leukemia: Experimental Patients receive oral nilotinib twice daily beginning on the day of engraftment (between 21 and 42 days after transplant) and continuing until day 445 in the absence of disease progression or unacceptable toxicity.	Drug: nilotinib Given orally

Detailed Description:

OBJECTIVES:

Primary

To determine the safety of nilotinib when administered between days 81 and 445 after allogeneic hematopoietic stem cell transplantation (HSCT) in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia or chronic myelogenous leukemia.

Secondary

To quantify the BCR/ABL transcript load during tyrosine kinase inhibitor therapy in patients treated sequentially with imatinib mesylate and nilotinib from the time of engraftment.
To evaluate survival at 1 year in patients treated sequentially with imatinib mesylate and nilotinib from the time of engraftment.
To determine if imatinib mesylate can be coadministered with nilotinib in patients with rising levels of BCR/ABL on 2 consecutive occasions after HSCT.
To confirm that imatinib mesylate can be delivered at an average daily dose of 400 mg at least 85% of the time during the first 80 days after HSCT in the majority of adult patients.
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 of age) at least 70% of the time during the first 80 days after HSCT in patients with imatinib mesylate-resistant Ph+ leukemia.
To determine treatment efficacy success at 1 year post-transplant as demonstrated by complete hematological remission, absence of Philadelphia chromosome, and absence of treatment failure in these patients.

OUTLINE: This is a multicenter study.

Patients undergo standard conditioning therapy followed by allogeneic hematopoietic stem cell transplantation on day 0. Patients proceed to further therapy based on known response to imatinib mesylate (sensitive or resistant).

Imatinib mesylate-sensitive leukemia: Patients receive oral imatinib mesylate once daily beginning on the day of engraftment (between 21 and 42 days after transplant) and continuing until day 80. Patients then receive oral nilotinib twice daily on days 81-445 in the absence of disease progression or unacceptable toxicity.
Imatinib mesylate-resistant leukemia: Patients receive oral nilotinib twice daily beginning on the day of engraftment (between 21 and 42 days after transplant) and continuing until day 445 in the absence of disease progression or unacceptable toxicity.

Bone marrow and blood samples are collected periodically for laboratory studies. Samples are analyzed by PCR for quantitative levels of the BCR/ABL gene. Pharmacokinetic and flow cytometry studies are also performed.

After completion of study treatment, patients are followed periodically.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of one of the following:
- Acute lymphoblastic leukemia (ALL) in complete cytogenetic remission immediately before conditioning therapy
- Chronic myelogenous leukemia (CML) in accelerated phase, blast crisis, or blast crisis remission as defined by WHO criteria
- CML in first chronic phase (if ≤ 17 years of age) OR CML in second chronic phase or beyond (any age)
Philadelphia chromosome-positive (Ph+) disease, as characterized by the p^190 and/or p^210 BCR/ABL gene rearrangement
No known T315I mutation
- Patients with minimal residual disease must be screened for the T315I mutation and other mutations
No aberrant antigen expression on ≥ 5% of marrow leukemic blasts by multidimensional flow cytometric assay immediately before conditioning therapy
- Patients with CML in chronic phase are exempt from flow cytometry screening
Must not be resistant or intolerant to nilotinib
Planning to undergo allogeneic hematopoietic stem cell transplantation
- Matched related or unrelated donor available
No CNS involvement with leukemia
- Patients with CML (chronic phase [CP] or accelerated phase [AP]) are exempt from CNS involevment screening

PATIENT CHARACTERISTICS:

Life expectancy ≥ 2 months
- Must not be severely limited by another disease
ANC ≥ 1,500/mm³ (filgrastim [G-CSF] allowed to maintain count)
Platelet count > 20,000/mm³
Creatinine < 1.5 times upper limit of normal (ULN)
Serum potassium, phosphorus, magnesium, and calcium normal OR correctable with supplements prior to first dose of study drug
Serum amylase and lipase ≤ 1.5 times ULN
AST and ALT ≤ 3 times ULN
Conjugated bilirubin < 3 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for up to 3 months after completion of study treatment
Body surface area ≥ 1 m²
No impaired cardiac function, including any of the following:
- Complete left bundle branch block or bifascicular block (i.e., right bundle branch block plus left anterior hemiblock) or use of ventricular-paced pacemaker
- LVEF < 45% by MUGA or ECHO
- 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 (i.e., heart rate < 50 beats per minute)
- QTcF > 450 msec on screening ECG
No myocardial infarction within the past year
No other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, unstable angina)
No hypersensitivity to imatinib mesylate or nilotinib

PRIOR CONCURRENT THERAPY:

No prior autologous or nonmyeloablative stem cell transplantation
No concurrent grapefruit or grapefruit juice

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00702403

Locations

United States, Washington
Fred Hutchinson Cancer Research Center	Recruiting
Seattle, Washington, United States, 98109-1024
Contact: Paul Carpenter, MD 206-667-3786

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Paul Carpenter, MD

Fred Hutchinson Cancer Research Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	Fred Hutchinson Cancer Research Center ( Paul Carpenter )
Study ID Numbers:	CDR0000597945, FHCRC-2223.00, FHCRC-IR-6691, NOVARTIS-FHCRC-2223.00
Study First Received:	June 19, 2008
Last Updated:	January 6, 2009
ClinicalTrials.gov Identifier:	NCT00702403
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia
Philadelphia chromosome positive childhood precursor acute lymphoblastic leukemia
Philadelphia chromosome positive chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia

childhood chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
childhood acute lymphoblastic leukemia in remission

Study placed in the following topic categories:

Chromosomal abnormalities
Philadelphia Chromosome
Blast Crisis
Leukemia, Lymphoid
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Chronic myelogenous leukemia
Hematologic Diseases
Myeloproliferative Disorders
Leukemia, Myeloid
Leukemia, Myeloid, Chronic-Phase

Acute lymphoblastic leukemia, adult
Imatinib
Leukemia
Lymphatic Diseases
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chromosome Aberrations
Bone Marrow Diseases
Lymphoproliferative Disorders
Lymphoma

Additional relevant MeSH terms:

Neoplasms
Pathologic Processes
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents

Therapeutic Uses
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions
Translocation, Genetic

ClinicalTrials.gov processed this record on January 15, 2009