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B-cell Adult Acute Lymphoblastic LeukemiaPhase 2NCT01670084

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

A Phase 2 study testing nilotinib, rituximab and cyclophosphamide in people with B-cell Adult Acute Lymphoblastic Leukemia and Blastic Phase Chronic Myelogenous Leukemia, run by Mayo Clinic at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
nilotinib, rituximab and cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesUnited States
Study dates
Dec 2012to Sep 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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])
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  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

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

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the clinical efficacy (2-year disease-free survival rate) of nilotinib and combination chemotherapy in adult patients newly diagnosed with Philadelphia chromosome positive B-cell acute lymphoblastic leukemia or blast crisis of chronic myeloid leukemia.

SECONDARY OBJECTIVES:

  1. Determine the 2-year overall survival rate. II. Determine the complete response (CR) rates (hematological, cytogenetic, and molecular) in patients treated with this regimen.

III. Determine the CR duration in patients treated with this regimen. IV. Assess the safety and toxicity of this regimen by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

TERTIARY OBJECTIVES:

  1. Assess the prognostic and predictive factors for patients treated with this regimen.

II. Assess the cerebrospinal fluid (CSF) penetration for Nilotinib (CSF Nilotinib levels) in humans.

III. Assess the Abelson (ABL) kinase domain mutations frequency at diagnosis, during therapy, and at relapse.

OUTLINE:

INDUCTION AND CONSOLIDATION SCHEDULE A (COURSES 1, 3, 5, 7): Patients receive cyclophosphamide intravenously (IV) twice daily (BID) over 2 hours on days 1-3, mesna IV continuously on days 1-3, doxorubicin hydrochloride IV push on day 4, vincristine sulfate IV on days 4 and 11, dexamethasone IV or orally (PO) on days 1-4 and 11-14, methotrexate intrathecally (IT) on day 2, cytarabine IT on day 8, and nilotinib PO BID on days 1-14. Patients with CD20-positive disease also receive rituximab IV on days 1 and 11.

INDUCTION AND CONSOLIDATION SCHEDULE B (COURSES 2, 4, 6, 8): Patients receive methotrexate IV continuously over 24 hours on day 1, cytarabine IV over 2 hours on days 2-3, leucovorin calcium IV every 6 hours on days 2-3, methotrexate IT on day 2, cytarabine IT on day 8, and nilotinib PO BID on days 1-14. Patients with CD20-positive disease also receive rituximab IV on days 1 and 11.

MAINTENANCE (COURSES 9-32): Patients receive nilotinib PO BID on days 1-28 (days 1-14 for minimal residual disease [MRD]-positive patients), vincristine sulfate IV on day 1, and prednisone PO on days 1 to 5. Patients also receive rituximab IV on day 1 of each course if CD20-positive, every sixth course if MRD-negative, or every third course if MRD-positive.

INTENSIFICATION: Patients receive treatment as in Schedule A in courses 14 and 21 of maintenance therapy and treatment as in Schedule B in courses 15 and 22 of maintenance therapy.

DELAYED MAINTENANCE (COURSES 33-36): Patients receive nilotinib PO BID on days 1 to 84. Treatment repeats every 84 days for up to 4 courses.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6-12 months for 4 years.

Medical subject headings
Blast Crisis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • nilotinibDrug

    Also called AMN 107, Tasigna

    Given PO

  • rituximabBiological

    Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8

    Given IV

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • doxorubicin hydrochlorideDrug

    Also called ADM, ADR, Adria, Adriamycin PFS

    Given IV

  • vincristine sulfateDrug

    Also called leurocristine sulfate, VCR, Vincasar PFS

    Given IV

  • methotrexateDrug

    Also called amethopterin, Folex, methylaminopterin, Mexate

    Given IV or IT

  • cytarabineDrug

    Also called ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U

    Given IV or IT

  • prednisoneDrug

    Also called DeCortin, Deltra

    Given PO

  • mesnaDrug

    Also called mercaptoethane sulfonate, Mesnex, MSA

    Given IV

  • dexamethasoneDrug

    Also called Aeroseb-Dex, Decaderm, Decadron, DM

    Given IV or PO

  • leucovorin calciumDrug

    Also called CF, CFR, LV

    Given IV

Study groups in NCT01670084
Study groupRoleWhat they receive
Treatment (nilotinib, combination chemotherapy)ExperimentalSee Detailed Description
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2 years

Secondary outcomes (4)

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

    Measured: 2 years

  2. 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

    Measured: 56 days

  3. 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

    Measured: Up to 4 years

  4. 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

    Measured: Up to 30 days after last dose of study drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2012 (estimated)
  2. Study startDec 2012
  3. Primary completionSep 2015 (estimated)
  4. Study completionSep 2017 (estimated)

Why it stopped: No Accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01670084
Sponsor's protocol ID
MC1184
Other IDs
NCI-2012-01061
Status last verified
Oct 2015
First submitted
17 Aug 2012
Last updated
30 Oct 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing nilotinib, rituximab and cyclophosphamide in people with B-cell Adult Acute Lymphoblastic Leukemia and Blastic Phase Chronic Myelogenous Leukemia, run by Mayo Clinic at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 58 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 30 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01670084.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2015.

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