Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Mayo Clinic
Sponsor:
Information provided by (Responsible Party):
Aref Al-Kali, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01670084
First received: August 17, 2012
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
B-cell Adult Acute Lymphoblastic Leukemia
Blastic Phase Chronic Myelogenous Leukemia
Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia
Untreated Adult Acute Lymphoblastic Leukemia
Drug: nilotinib
Biological: rituximab
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
Drug: methotrexate
Drug: cytarabine
Drug: prednisone
Drug: mesna
Drug: dexamethasone
Drug: leucovorin calcium
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Combination Nilotinib and Hyper-CVAD in Patients Newly Diagnosed With Philadelphia-Chromosome Positive Acute Lymphoblastic Leukemia or Chronic Myeloid Leukemia Blast-Phase Lymphoid Lineage

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall survival time, defined as the time from registration to death due to any cause out to 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 56 days ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Up to 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 44
Study Start Date: December 2012
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (nilotinib, combination chemotherapy)
See Detailed Description
Drug: nilotinib
Given PO
Other Names:
  • AMN 107
  • Tasigna
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: methotrexate
Given IV or IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cytarabine
Given IV or IT
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra
Drug: mesna
Given IV
Other Names:
  • mercaptoethane sulfonate
  • Mesnex
  • MSA
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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%
    • Clinically significant resting brachycardia (< 50 beats per minute)
    • Corrected QT interval (QTc) > 450 msec on baseline ECG; if QTc > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
    • Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension)
    • History of or presence of clinically significant ventricular or atrial tachyarrhythmias
  • Patients receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450 3A4 (CYP3A4); use of the following strong or moderate inhibitors are prohibited =< 7 days prior to registration:

    • Strong Inhibitors of CYP3A4; > 5-fold increase in the plasma area under the curve (AUC) values or more than 80% decrease in clearance

      • Indinavir (Crixivan®)
      • Nelfinavir (Viracept®)
      • Atazanavir (Reyataz®)
      • Ritonavir (Norvir®)
      • Clarithromycin (Biaxin®, Biaxin XL®)
      • Itraconazole (Sporanox®)
      • Ketoconazole (Nizoral®)
      • Nefazodone (Serzone®)
      • Saquinavir (Fortovase®, Invirase®)
      • Telithromycin (Ketek®)
    • Moderate Inhibitors of CYP3A4; > 2-fold increase in the plasma AUC values or 50-80% decrease in clearance

      • Aprepitant (Emend®)
      • Erythromycin (Erythrocin®, E.E.S. ®, Ery-Tab®, Eryc®, EryPed®, PCE®)
      • Fluconazole (Diflucan®)
      • Grapefruit juice
      • Verapamil (Calan®, Calan SR®, Covera-HS®, Isoptin SR®, Verelan®, Verelan PM®)
      • Diltiazem (Cardizem®, Cardizem CD®, Cardizem LA®, Cardizem SR®, Cartia XT™, Dilacor XR®, Diltia XT®, Taztia XT™, Tiazac®)
  • Patients receiving any medications or substances that are inducers of CYP3A4; use of the following inducers are prohibited =< 7 days prior to registration

    * Inducers of CYP3A4

    • Efavirenz (Sustiva®)
    • Nevirapine (Viramune®)
    • Carbamazepine (Carbatrol®, Epitol®, Equetro™, Tegretol®, Tegretol-XR®)
    • Modafinil (Provigil®)
    • Phenobarbital (Luminal®)
    • Phenytoin (Dilantin®, Phenytek®)
    • Pioglitazone (Actos®)
    • Rifabutin (Mycobutin®)
    • Rifampin (Rifadin®)
    • St. John's wort
  • Patients currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug
  • Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery)
  • Acute or chronic pancreatic disease
  • Known cytopathologically confirmed central nervous system (CNS) infiltration
  • Acute or chronic liver disease or severe renal disease considered unrelated to the cancer
  • History of significant congenital or acquired bleeding disorder unrelated to cancer
  • Major surgery =< 4 weeks prior to registration or not recovered from prior surgery
  • Treatment with other investigational agents =< 14 days of registration
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01670084

Locations
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Mayo Clinic Clinical Trials Referral Office    507-538-7623      
Principal Investigator: Raoul Tibes, M.D., Ph.D.         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Contact: Aref Al-Kali, M.D.    507-538-0591    alkali.aref@mayo.edu   
Principal Investigator: Aref Al-Kali, M.D.         
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Aref Al-Kali, M.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: Aref Al-Kali, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01670084     History of Changes
Other Study ID Numbers: MC1184, NCI-2012-01061
Study First Received: August 17, 2012
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Blast Crisis
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Abnormal Karyotype
Neoplasms by Histologic Type
Neoplasms
Cell Transformation, Neoplastic
Carcinogenesis
Neoplastic Processes
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Pathologic Processes
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Mesna
Levoleucovorin
Antibodies, Monoclonal
Cyclophosphamide
Cytarabine
Methotrexate
Rituximab

ClinicalTrials.gov processed this record on August 21, 2014