NCT01670084

Brief Summary

In this study researchers want to find out more about the side effects of a new drug for Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) and chronic myelogenous leukemia (CML) blastic phase (BP) and if this disease will respond better to nilotinib combined with standard hyper-CVAD therapy rather than hyper-CVAD alone. Hyper-CVAD is a combination of cyclophosphamide, mesna, vincristine (vincristine sulfate), doxorubicin (doxorubicin hydrochloride), dexamethasone, methotrexate, cytarabine, and rituximab (only for patients with cluster of differentiation \[CD\]20 positive disease). Researchers don't know all the ways that this drug may affect people

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Dec 2012

Longer than P75 for phase_2

Geographic Reach
1 country

2 active sites

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 17, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 21, 2012

Completed
3 months until next milestone

Study Start

First participant enrolled

December 1, 2012

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2015

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2017

Completed
Last Updated

October 30, 2015

Status Verified

October 1, 2015

Enrollment Period

2.8 years

First QC Date

August 17, 2012

Last Update Submit

October 29, 2015

Conditions

Outcome Measures

Primary Outcomes (1)

  • Disease-free survival rate, defined as a patient who is alive and relapse-free, in patients who achieve a CR during the first 2 courses out to 2 years

    The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.

    2 years

Secondary Outcomes (4)

  • Overall survival time, defined as the time from registration to death due to any cause out to 2 years

    2 years

  • Complete response (CR) rate estimated by the number of patients achieving an objective status of CR during the first 2 courses of treatment divided by the total number of evaluable patients

    56 days

  • Complete response (CR) as defined for all evaluable patients who have achieved a CR as the date at which the patient's objective status is first noted to be a CR to the earliest date relapse is documented out to 4 years

    Up to 4 years

  • Maximum grade for each type of adverse event, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0

    Up to 30 days after last dose of study drug

Study Arms (1)

Treatment (nilotinib, combination chemotherapy)

EXPERIMENTAL

See Detailed Description

Drug: nilotinibBiological: rituximabDrug: cyclophosphamideDrug: doxorubicin hydrochlorideDrug: vincristine sulfateDrug: methotrexateDrug: cytarabineDrug: prednisoneDrug: mesnaDrug: dexamethasoneDrug: leucovorin calcium

Interventions

Given PO

Also known as: AMN 107, Tasigna
Treatment (nilotinib, combination chemotherapy)
rituximabBIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Treatment (nilotinib, combination chemotherapy)

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Treatment (nilotinib, combination chemotherapy)

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF
Treatment (nilotinib, combination chemotherapy)

Given IV

Also known as: leurocristine sulfate, VCR, Vincasar PFS
Treatment (nilotinib, combination chemotherapy)

Given IV or IT

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX
Treatment (nilotinib, combination chemotherapy)

Given IV or IT

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside
Treatment (nilotinib, combination chemotherapy)

Given PO

Also known as: DeCortin, Deltra
Treatment (nilotinib, combination chemotherapy)
mesnaDRUG

Given IV

Also known as: mercaptoethane sulfonate, Mesnex, MSA
Treatment (nilotinib, combination chemotherapy)

Given IV or PO

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM
Treatment (nilotinib, combination chemotherapy)

Given IV

Also known as: CF, CFR, LV
Treatment (nilotinib, combination chemotherapy)

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Untreated, histological confirmed Philadelphia positive B-cell acute lymphoblastic leukemia or chronic myeloid leukemia blast-phase lymphoid lineage (bilineal, biphenotypic or undifferentiated) per World Health Organization (WHO) criteria; NOTE: Dexamethasone (or corticosteroids) use is allowed if needed before starting chemotherapy; prior imatinib or dasatinib therapy for CML chronic phase (CP) or accelerated phase (AP) is allowed
  • Molecular or cytogenetic documentation of BCR-ABL fusion gene via any of the following: reverse transcriptase-polymerase chain reaction (RT-PCR), G-banding, or fluorescence in situ hybridization (FISH) testing from peripheral blood and/or bone marrow sampling
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Magnesium/potassium/phosphorus within normal limits (WNL)
  • Serum amylase =\< 1.5 x upper limit of normal (ULN)
  • Lipase =\< 1.5 x ULN
  • Total bilirubin \< 1.5 x ULN (does not apply to patients with isolated hyperbilirubinemia \[e.g., Gilbert's disease\], in this situation the direct bilirubin =\< 2 x ULN)
  • Alkaline phosphatase =\< 3 x ULN
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 3 x ULN
  • Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 3 x ULN
  • Creatinine =\< 1.5 x ULN
  • Negative serum pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
  • Provide informed written consent
  • Willing to return to Mayo Clinic Rochester or Mayo Clinic Arizona for follow-up during the active monitoring phase of the study
  • Willing to provide CSF and blood samples for correlative research purposes

You may not qualify if:

  • Any of the following because this study involves investigational agent(s) whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the study and for 3 months after completion of study treatment
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive (even if on highly active antiretroviral therapy \[HAART\])
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Other active malignancy =\< 3 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
  • History of myocardial infarction =\< 12 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • Previous treatment with chemotherapy or any other tyrosine kinase inhibitor (prior imatinib or dasatinib for CML-CP/-AP is allowed)
  • Impaired cardiac function including any one of the following:
  • Inability to monitor the QT interval on electrocardiogram (ECG)
  • Congenital long QT syndrome or a known family history of long QT syndrome
  • Cardiac ejection fraction (EF) \< 45%
  • +43 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Blast CrisisLeukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

nilotinibRituximabCyclophosphamideDoxorubicinVincristineMethotrexatemerphosCytarabinePrednisoneMesnaDexamethasoneCalcium DobesilateLeucovorin

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsCell Transformation, NeoplasticCarcinogenesisNeoplastic ProcessesMyeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizinesAminopterinPterinsPteridinesCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingArabinonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesPregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, AcyclicSulfhydryl CompoundsSulfur CompoundsSulfonic AcidsSulfur AcidsPregnadienetriolsSteroids, FluorinatedBenzenesulfonatesBenzene DerivativesArylsulfonatesArylsulfonic AcidsFormyltetrahydrofolatesTetrahydrofolatesFolic AcidCoenzymesEnzymes and Coenzymes

Study Officials

  • Aref Al-Kali, M.D.

    Mayo Clinic

    STUDY CHAIR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 17, 2012

First Posted

August 21, 2012

Study Start

December 1, 2012

Primary Completion

September 1, 2015

Study Completion

September 1, 2017

Last Updated

October 30, 2015

Record last verified: 2015-10

Locations