Trial record 1 of 341 for:    "Anaplastic large cell lymphoma"
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Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma

This study is currently recruiting participants.
Verified December 2013 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01979536
First received: November 4, 2013
Last updated: January 20, 2014
Last verified: December 2013
  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.


Condition Intervention Phase
Stage II Childhood Anaplastic Large Cell Lymphoma
Stage III Childhood Anaplastic Large Cell Lymphoma
Stage IV Childhood Anaplastic Large Cell Lymphoma
Drug: brentuximab vedotin
Drug: crizotinib
Drug: dexamethasone
Drug: ifosfamide
Drug: methotrexate
Drug: cytarabine
Drug: etoposide
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II 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) IND # 117117

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Occurrence of grade 3+ non-hematologic adverse events, using the National Cancer Institute (NCI) CTCAE version (v)4.0 [ Time Frame: Up to 60 months ] [ Designated as safety issue: Yes ]
    These adverse event rates will be compared to the null hypothesis rate of 5% using an exact test for proportions. Toxicities will be summarized by individual toxicity counts and incidence rate separated by arm and course.

  • EFS [ Time Frame: Time from study entry until progressive disease, relapse, or death, assessed up to 60 months ] [ Designated as safety issue: No ]
    The EFS for each of the treatment regimens will be compared to the fixed standard using Woolson's 1-sample log-rank test.


Secondary Outcome Measures:
  • Changes on levels of MRD [ Time Frame: Baseline up to day 21 (course 1) ] [ Designated as safety issue: No ]
    Analyzed using the log-rank test.


Estimated Enrollment: 140
Study Start Date: November 2013
Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm BV (brentuximab vedotin, combination chemotherapy)

COURSE A (COURSES 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 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.

Drug: brentuximab vedotin
Given IV
Other Names:
  • Adcetris
  • anti-CD30 ADC SGN-35
  • anti-CD30 antibody-drug conjugate SGN-35
  • antibody-drug conjugate SGN-35
  • SGN-35
Drug: dexamethasone
Given PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Drug: methotrexate
Given IT and IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cytarabine
Given IT and IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
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
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm CZ (crizotinib, combination chemotherapy)

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.

Drug: crizotinib
Given PO
Other Names:
  • c-met/hepatocyte growth factor receptor tyrosine kinase inhibitor PF-02341066
  • c-met/HGFR tyrosine kinase inhibitor PF-02341066
  • MET Tyrosine Kinase Inhibitor PF-02341066
  • PF-02341066
Drug: dexamethasone
Given PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Drug: methotrexate
Given IT and IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cytarabine
Given IT and IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
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
Other: laboratory biomarker analysis
Correlative studies

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 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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion 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 >= 8 weeks
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • 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
  • 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
  • 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
  • Patients who weigh < 10 kg are not eligible
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01979536

  Show 27 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Eric Lowe Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01979536     History of Changes
Other Study ID Numbers: NCI-2013-02167, NCI-2013-02167, COG-ANHL12P1, ANHL12P1, ANHL12P1, U10CA098543
Study First Received: November 4, 2013
Last Updated: January 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Anaplastic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, T-Cell
Cyclophosphamide
Cytarabine
Methotrexate
Ifosfamide
Isophosphamide mustard
Etoposide phosphate
Dexamethasone
Doxorubicin
Etoposide
Antibodies, Monoclonal
Immunoconjugates
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014