Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma
Condition: Anaplastic Large Cell Lymphoma, ALK-Positive; Ann Arbor Stage II Noncutaneous Childhood Anaplastic Large Cell Lymphoma; Ann Arbor Stage III Noncutaneous Childhood Anaplastic Large Cell Lymphoma; Ann Arbor Stage IV Noncutaneous Childhood Anaplastic Large Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Anaplastic
Intervention: Brentuximab Vedotin; Crizotinib; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin Hydrochloride; Etoposide; Ifosfamide; Methotrexate
Intervention description: Given IV; Given PO; Given IV; Given IT and IV; Given PO or IV; Given IV; Given IV; Given IV; Given IT and IV
Intervention MeSH terms: Cytarabine; Dexamethasone; Dexamethasone acetate; Cyclophosphamide; Ifosfamide; Isophosphamide mustard; Doxorubicin; Liposomal doxorubicin; Methotrexate; Etoposide; Etoposide phosphate; Brentuximab Vedotin; Podophyllotoxin; Crizotinib; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal; BB 1101; Immunoconjugates; Tyrosine Protein Kinase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 137.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No

Summary:

      This partially randomized phase II trial studies how well brentuximab vedotin or crizotinib
      and combination chemotherapy works in treating patients with newly diagnosed stage II-IV
      anaplastic large cell lymphoma. Brentuximab vedotin is a monoclonal antibody, called
      brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive
      cancer cells in targeted way and delivers vedotin to kill them. Crizotinib and methotrexate
      may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
      Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either
      by killing the cells, by stopping them from dividing, or by stopping them from spreading. It
      is not yet known whether brentuximab vedotin and combination chemotherapy is more effective
      than crizotinib and combination chemotherapy in treating anaplastic large cell lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Newly diagnosed patients with histologically proven ALCL (International Classification
             of Diseases for Oncology [ICD-0] code: 9714/3)

          -  Disease must be cluster of differentiation (CD)30 positive

          -  Disease must be anaplastic lymphoma kinase (ALK) positive (defined by local
             institutional standards)

          -  Patients must have stage II, III, or IV disease

          -  Patients must have a life expectancy of >= 8 weeks

          -  Adequate Liver Function Defined As:

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
             enrollment)

          -  Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x
             upper limit of normal (ULN) for age; for the purpose of this study, the ULN for ALT is
             45 U/L (within 7 days prior to enrollment)

          -  If the lab abnormality is thought to be due to the lymphoma the patient is eligible
             and dose adjustments should be made

          -  Adequate Cardiac Function Defined As:

          -  Shortening fraction of >= 27% by echocardiogram, or

          -  Ejection fraction of >= 50% by radionuclide angiogram

          -  Adequate Pulmonary Function Defined As:

          -  Patients with a history of pulmonary dysfunction must have no evidence of dyspnea at
             rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry >
             92% while breathing room air unless current dysfunction is due to the lymphoma in
             which case the patient is eligible

        Exclusion Criteria:

          -  Patients with central nervous system (CNS) disease are not eligible

          -  Patients with disease limited to the skin are not eligible, regardless of how
             wide-spread

          -  Patients with stage I disease are not eligible

          -  Patients who have received any prior cytotoxic chemotherapy for the current diagnosis
             of ALCL or any cancer diagnosed previously are not eligible

          -  Previous steroid treatment and/or radiation treatment is not allowed unless it is for
             the emergent management of a mediastinal mass; emergent steroid treatment and/or
             radiation treatment should stop once protocol therapy is initiated

          -  Intrathecal chemotherapy prior to enrollment is allowed for the current diagnosis of
             ALCL as long as adequate cerebrospinal fluid (CSF) is obtained prior to administration
             of the intrathecal chemotherapy and subsequently demonstrated to be negative for ALCL

          -  Female patients who are pregnant are not eligible; pregnancy tests must be obtained in
             girls who are post menarchal

          -  Lactating females are not eligible unless they have agreed not to breastfeed their
             infants

          -  Sexually active patients of reproductive potential are not eligible unless they agree
             to use an effective contraceptive method for the duration of treatment and for 3
             months after stopping treatment

          -  Patients with Down syndrome are not eligible due to the amount of methotrexate and
             potential for side effects

          -  Patients with an immunodeficiency that existed prior to diagnosis such as primary
             immunodeficiency syndromes or organ transplant recipients are not eligible

          -  Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates with narrow
             therapeutic indices: Patients chronically receiving medications known to be
             metabolized by CYP3A4 and with narrow therapeutic indices including pimozide,
             aripiprazole, triazolam, ergotamine and halofantrine are not eligible; the topical use
             of these medications (if applicable) is allowed

          -  CYP3A4 inhibitors: patients chronically receiving drugs that are known potent CYP3A4
             inhibitors within 7 days prior to study enrollment, including but not limited to
             ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir, indinavir,
             nelfinavir, saquinavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit
             juice are not eligible; the topical use of these medications (if applicable), e.g. 2%
             ketoconazole cream, is allowed

          -  CYP3A4 inducers: patients chronically receiving drugs that are known potent CYP3A4
             inducers within 12 days prior to study enrollment, including but not limited to
             carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, ritonavir, and St.
             John's wort are not eligible; the topical use of these medications (if applicable) is
             allowed

          -  Patients that are known to be positive for human immunodeficiency virus (HIV) are not
             eligible; note: inclusion of HIV positive patients will be considered at a later date

          -  Patients who weigh < 10 kg are not eligible