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

NCT00702403 | Completed Phase 1 Results DMC

• 4 other identifiers: 2223.00NCI-2010-00402P30CA015704P01CA018029
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

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

Outcome Measures

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.

  Up to 365 days post-transplant

Secondary Outcomes (4)

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

  Up to 1 year

• Survival

  Up to 3 years

• Patients Alive With Out Relapse

  Up to 1 year

• Relapse

  1 and 3 years

Study Arms (1)

Treatment (prophylactic inhibition of BCR-ABL tyrosine kinase)

EXPERIMENTAL

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

nilotinib DRUG

Given PO

Also known as: AMN 107, Tasigna

Treatment (prophylactic inhibition of BCR-ABL tyrosine kinase)

imatinib mesylate DRUG

Given PO

Also known as: CGP 57148, Gleevec, Glivec

Treatment (prophylactic inhibition of BCR-ABL tyrosine kinase)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (prophylactic inhibition of BCR-ABL tyrosine kinase)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Stanford University Hospitals and Clinics

Stanford, California, 94305, United States

Location

H Lee Moffitt Cancer Center and Research Institute Phase 2 Consortium

Tampa, Florida, 33612, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Blast Crisis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

nilotinib; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Dr. Paul A. Carpenter
• Organization: Fred Hutchinson Cancer Research Center

pcarpent@fredhutch.org

(206) 667-5191

Study Officials

• Paul Carpenter

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 19, 2008
• First Posted: June 20, 2008
• Study Start: August 14, 2008
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: August 10, 2017
• Results First Posted: May 15, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)