Clinical Trials /

Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma

NCT01979536

Description:

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.

Related Conditions:
  • Anaplastic Large Cell Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma
  • Official Title: A Randomized Phase 2 Trial of Brentuximab Vedotin (SGN35, NSC# 749710), or Crizotinib (NSC#749005, Commercially Labeled) in Combination With Chemotherapy for Newly Diagnosed Patients With Anaplastic Large Cell Lymphoma (ALCL)

Clinical Trial IDs

  • ORG STUDY ID: NCI-2013-02167
  • SECONDARY ID: NCI-2013-02167
  • SECONDARY ID: s14-01970
  • SECONDARY ID: COG-ANHL12P1
  • SECONDARY ID: ANHL12P1
  • SECONDARY ID: ANHL12P1
  • SECONDARY ID: U10CA180886
  • SECONDARY ID: U10CA098543
  • NCT ID: NCT01979536

Conditions

  • 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
  • CD30-Positive Neoplastic Cells Present

Interventions

DrugSynonymsArms
Brentuximab VedotinADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35Arm BV (brentuximab vedotin, combination chemotherapy)
CrizotinibMET Tyrosine Kinase Inhibitor PF-02341066, PF-02341066, PF-2341066, XalkoriArm CZ (crizotinib, combination chemotherapy)
Cyclophosphamide(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719Arm BV (brentuximab vedotin, combination chemotherapy)
Cytarabine.beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453Arm BV (brentuximab vedotin, combination chemotherapy)
DexamethasoneAacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDexArm BV (brentuximab vedotin, combination chemotherapy)
Doxorubicin Hydrochloride5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, RubexArm BV (brentuximab vedotin, combination chemotherapy)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16Arm BV (brentuximab vedotin, combination chemotherapy)
IfosfamideAsta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942Arm BV (brentuximab vedotin, combination chemotherapy)
MethotrexateAbitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039Arm BV (brentuximab vedotin, combination chemotherapy)

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. 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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the tolerability of brentuximab vedotin given in combination with standard
      chemotherapy (anaplastic large cell lymphoma [ALCL]99) and to determine the tolerability of
      crizotinib given in combination with chemotherapy (ALCL99).

      II. To estimate the event free survival (EFS) of Arm brentuximab vedotin (BV) and Arm
      crizotinib (CZ) and contrast these to historical control data.

      SECONDARY OBJECTIVES:

      I. To determine the prognostic significance of minimal disseminated disease (MDD) at
      diagnosis and minimal residual disease (MRD) as measured by real-time (RT)-polymerase chain
      reaction (PCR) in peripheral blood.

      OUTLINE: Patients are assigned or randomized into 1 of 2 treatment arms.

      ARM BV:

      COURSE A (CYCLES 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 1-30 minutes every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2
      hours on days 4 and 5.

      COURSE B (CYCLES 2, 4, AND 6): Patients receive brentuximab vedotin, dexamethasone, and
      methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 15-30
      minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5.

      ARM CZ:

      COURSE A (CYCLES 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 (CYCLES 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 cycles 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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm BV (brentuximab vedotin, combination chemotherapy)ExperimentalCOURSE A (CYCLES 1, 3, AND 5): Patients receive brentuximab vedotin IV over 30 minutes on day 1, dexamethasone PO 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 1-30 minutes every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2 hours on days 4 and 5. COURSE B (CYCLES 2, 4, AND 6): Patients receive brentuximab vedotin, dexamethasone, and methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 15-30 minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5.
  • Brentuximab Vedotin
  • Cyclophosphamide
  • Cytarabine
  • Dexamethasone
  • Doxorubicin Hydrochloride
  • Etoposide
  • Ifosfamide
  • Methotrexate
Arm CZ (crizotinib, combination chemotherapy)ExperimentalCOURSE A (CYCLES 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 (CYCLES 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.
  • Crizotinib
  • Cyclophosphamide
  • Cytarabine
  • Dexamethasone
  • Doxorubicin Hydrochloride
  • Etoposide
  • Ifosfamide
  • Methotrexate

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

          -  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

          -  Shortening fraction of >= 27% by echocardiogram, or

          -  Ejection fraction of >= 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 >
             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
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Occurrence of grade 3+ non-hematologic adverse events
Time Frame:Up to 60 months
Safety Issue:
Description:Will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Toxicities will be summarized by individual toxicity counts and incidence rate separated by arm and course.

Secondary Outcome Measures

Measure:Changes on levels of minimal residual disease
Time Frame:Baseline up to day 21 (course 1)
Safety Issue:
Description:Analyzed using the log-rank test.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

August 10, 2021