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Title:
ANHL12P1, A Randomized Phase II Trial of Brentuximab Vedotin or Crizotinib in Combination with Chemotherapy for Newly Diagnosed Patients with Anaplastic Large Cell Lymphoma (ALCL)
Protocol Number:
PANHL12P1
Phase:
Phase II
Physician:
Stacy Cooper
Sites:
Johns Hopkins Kimmel Cancer Center in Baltimore
Purpose:
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. Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells. 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 or by stopping them from dividing. 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:
Ages Eligible for Study: up to 21 YearsGenders Eligible for Study: BothAccepts Healthy Volunteers: NoCriteriaInclusion Criteria: Newly diagnosed patients with histologically proven anaplastic large cell lymphoma (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 greater than equal to 8 weeks Total bilirubin equal to less than 1.5 x upper limit of normal (ULN) for age Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) less than 2.5 x upper limit of normal (ULN) for age; for the purpose of this study, the ULN for ALT is 45 U/L If the lab abnormality is thought to be due to the lymphoma the patient is eligible and dose adjustments should be made Shortening fraction of greater than equal to 27% by echocardiogram, or Ejection fraction of greater than equal to 50% by radionuclide angiogram 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 greater than 92% while breathing room air unless current dysfunction is due to the lymphoma in which case the patient is eligibleExclusion 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 Intrathecal chemotherapy prior to enrollment will not be allowed for the current diagnosis of ALCL unless the 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 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 CYP3A4 Inhibitors: Patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to itraconazole, clarithromycin, erythromycin, many non-nucleoside reverse transcriptase inhibitors (NNRTIs), diltiazem, verapamil, and grapefruit juice are not eligible 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, rifampin, and St. John's wort are not eligible Patients positive for human immunodeficiency virus (HIV) are not eligible; Note: Inclusion of HIV positive patients will be considered at a later date
Treatment:
OUTLINE: Patients are randomized into 1 of 2 treatment arms.ARM BV:COURSE A (COURSES 1, 3, AND 5): Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1, dexamethasone orally (PO) twice daily (BID) or IV on days 1-5, ifosfamide IV over 60 minutes on days 1-5, methotrexate IV over 3 hours on day 1, cytarabine IV over 1 hour every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2 hours on days 4 and 5.COURSE B (COURSES 2, 4, AND 6): Patients receive brentuximab vedotin, dexamethasone, and methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 30-60 minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5.ARM CZ:COURSE A (COURSES 1, 3, AND 5): Patients receive crizotinib PO BID on days 1-21 and dexamethasone, ifosfamide, methotrexate, cytarabine, and etoposide as in Arm BV, Course A.COURSE B (COURSES 2, 4, AND 6): Patients receive crizotinib as in Arm CZ, Course A and dexamethasone, cyclophosphamide, methotrexate, and doxorubicin hydrochloride as in Arm BV, Course B.In all arms, treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months.
Population:
Both
Last Update
03/05/2019 05:03 AM