Brentuximab Vedotin and Gemcitabine Hydrochloride in Treating Younger Patients With Relapsed or Refractory Hodgkin Lymphoma

  • Resize font
  • Print
  • Email
  • Facebook
  • Twitter
  • Google+
  • Pinterest

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase II, Phase IBiomarker/Laboratory analysis, TreatmentActive13 to 30NCINCI-2013-00107
COG-AHOD1221, AHOD1221, UM1CA097452, NCT01780662

Trial Description

Summary

This phase I/II trial studies the side effects and the best dose of brentuximab vedotin when given together with gemcitabine hydrochloride and to see how well they work in treating younger patients with Hodgkin lymphoma that has returned or does not respond to treatment. Monoclonal antibodies, such as brentuximab vedotin, may find cancer cells and help kill them. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving brentuximab vedotin together with gemcitabine hydrochloride may kill more cancer cells.

Further Study Information

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of brentuximab vedotin in combination with gemcitabine (gemcitabine hydrochloride) administered every three weeks to children with relapsed or primary refractory Hodgkin lymphoma (HL).

II. To define and describe the toxicities of brentuximab vedotin in combination with gemcitabine administered on this schedule.

III. To determine the complete response (CR) rate after treatment with four cycles of gemcitabine with brentuximab vedotin among patients with relapsed or refractory HL.

SECONDARY OBJECTIVES:

I. To preliminarily define the antitumor activity of brentuximab vedotin in combination with gemcitabine within the confines of a Phase 1 study.

II. To describe the overall response rate (ORR) after 4 cycles of therapy among patients with relapsed or refractory HL.

III. To describe the proportion of patients with HL able to mobilize an adequate yield of cluster of differentiation (CD) 34+ stem cells after gemcitabine with brentuximab vedotin.

IV. To describe the relationship between disease response among patients with HL and changes in thymus and activation-regulated chemokine (TARC) during treatment, and to determine if specific micro ribonucleic acid (miRNA) profiles correlate with response to treatment.

V. To describe the frequency of the Fc gamma receptor IIIa (FcγRIIIa)-158 valine (V)/phenylalanine (F) polymorphism among patients who experience pulmonary toxicity on this protocol.

OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase II study. (Phase I completed as of amendment 4)

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and gemcitabine hydrochloride IV over 100 minutes on days 1 and 8. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity. Patients with CR after any course may go off protocol therapy for stem cell transplant.

After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months.

Eligibility Criteria

Inclusion Criteria:

  • Patients must have had histologic verification of the malignancy at original diagnosis; patients must have histologic verification of recurrent Hodgkin disease at the time of relapse; no additional biopsy is required for patients with primary refractory disease (i.e. no prior CR)
  • PARTS A AND B: Patients with Hodgkin lymphoma (HL) are eligible for both the phase 1 and 2 portions, if they are in one of the following categories:
  • Primary refractory disease (i.e. no prior CR)
  • Very early relapse (< 6 months from the end of initial therapy, including chemotherapy ± radiation)
  • Advanced stage (III or IV) at diagnosis who relapse less than one year from the end of initial therapy
  • Note that patients with low-stage disease (IA or IIA) at initial diagnosis, who were treated with radiation alone or fewer than four cycles of chemotherapy will NOT be eligible
  • Patients must have measurable disease, documented by clinical and radiographic criteria
  • Patients must have a life expectancy of >= 8 weeks (>= 56 days)
  • Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
  • At least 14 days after the last dose of myelosuppressive chemotherapy (28 days if prior nitrosourea); Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of therapy
  • At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
  • At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
  • At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
  • At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
  • At least 14 days after local palliative radiation therapy (XRT) (small port); at least 150 days must have elapsed if prior total body irradiation (TBI), craniospinal XRT or if >= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
  • Patients with prior autologous or allogeneic stem cell transplant (SCT) are excluded from this study
  • At least 28 days must have elapsed since the most recent dose of bleomycin, to allow adequate time to detect evidence of bleomycin-related pulmonary toxicity
  • PART A: FOR PATIENTS WITH KNOWN BONE MARROW INVOLVEMENT (Completed as of Amendment 4)
  • Peripheral absolute neutrophil count (ANC) >= 1000/uL
  • Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • PART B: FOR PATIENTS WITHOUT KNOWN BONE MARROW INVOLVEMENT
  • Peripheral absolute neutrophil count (ANC) >= 750/uL
  • Platelet count >= 75,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • Patients with lymphoma metastatic to bone marrow who have granulocytopenia, anemia, and/or thrombocytopenia will be eligible for study but not evaluable for hematologic toxicity (in Part A, there will be a maximum of one per cohort); such patients must meet the blood counts as in Part A (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled in Part A must be evaluable for hematologic toxicity
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 OR
  • A serum creatinine based on age/gender as follows:
  • =< 0.6 mg/dL (for 1 to < 2 years of age)
  • =< 0.8 mg/dL (for 2 to < 6 years of age)
  • =< 1.0 mg/dL (for 6 to < 10 years of age)
  • =< 1.2 mg/dL (for 10 to < 13 years of age)
  • =< 1.4 mg/dL (for females >= 13 years of age)
  • =< 1.5 mg/dL (for males 13 to < 16 years of age)
  • =< 1.7 mg/dL (for males >= 16 years of age)
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age; for the purpose of this study, the ULN for SGPT is 45 U/L
  • Serum albumin >= 2 g/dL
  • No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry > 92% while breathing room air
  • Forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and forced vital capacity all > 50% predicted value; Note: pulmonary function testing is not required for children < 8 years old, or for any child who is developmentally unable to comply with pulmonary function testing
  • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
  • Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4) resulting from prior therapy must be < grade 2
  • All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria:

  • Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during protocol therapy and for at least 30 days after the last dose of brentuximab vedotin; abstinence is an acceptable method of birth control
  • Concomitant medications
  • Patients receiving stable or decreasing corticosteroids are not eligible for other concurrent conditions (e.g. asthma, autoimmune diseases, rash, documented adrenal insufficiency) are eligible for this study
  • Patients who are currently receiving another investigational drug are not eligible
  • Patients who are currently receiving other anti-cancer agents are not eligible
  • Patients who have an uncontrolled infection are not eligible
  • Patients with an immunodeficiency that existed prior to diagnosis, such as primary immunodeficiency syndromes, organ transplant recipients and children on current systemic immunosuppressive agents are not eligible
  • Patients known to be positive for human immunodeficiency virus (HIV) are not eligible
  • Prior therapy
  • Patients with prior exposure to brentuximab vedotin are not eligible; NOTE: prior exposure to gemcitabine is NOT an exclusion criterion
  • Patients who have undergone prior autologous or allogeneic SCT are not eligible
  • Patients with HL who were stage IA or IIA at initial diagnosis and treated with either radiation alone or < 4 cycles of chemotherapy are not eligible
  • Patients who have received a prior solid organ transplantation are not eligible
  • Patients with known hypersensitivity to Escherichia coli (E.coli)-derived proteins, filgrastim, or any component of filgrastim are not eligible
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

    Peter Cole, Principal Investigator

    Trial Sites

    U.S.A.

    Alabama
    Birmingham

    Children's Hospital of Alabama at University of Alabama at Birmingham

    Alyssa T Reddy
    Ph: 888-823-5923
    Email: ctsucontact@westat.com

    California
    Loma Linda

    Loma Linda University Cancer Institute at Loma Linda University Medical Center

    Albert Kheradpour
    Ph: 909-558-3375

    Los Angeles

    Children's Hospital Los Angeles

    Leo Mascarenhas
    Ph: 323-361-4110

    Oakland

    Children's Hospital and Research Center Oakland

    Carla B Golden
    Ph: 510-450-7600

    Orange

    Children's Hospital of Orange County

    Violet Shen
    Ph: 714-997-3000

    Palo Alto

    Lucile Packard Children's Hospital at Stanford University Medical Center

    Neyssa M Marina
    Ph: 650-498-7061
    Email: clinicaltrials@med.stanford.edu

    Sacramento

    Sutter Cancer Center

    Yung S Yim
    Ph: 415-209-2686
    Email: bernicl@sutterhealth.org

    University of California Davis Cancer Center

    Jay Michael S Balagtas
    Ph: 916-734-3089

    San Diego

    Rady Children's Hospital - San Diego

    William D Roberts
    Ph: 858-966-5934

    San Francisco

    UCSF Helen Diller Family Comprehensive Cancer Center

    Michelle L Hermiston
    Ph: 877-827-3222

    District of Columbia
    Washington

    Children's National Medical Center

    Jeffrey S Dome
    Ph: 202-884-2549

    Florida
    Hollywood

    Joe DiMaggio Children's Hospital

    Iftikhar Hanif
    Ph: 954-265-2234

    Orlando

    Arnold Palmer Hospital for Children

    Vincent F Giusti
    Ph: 321-841-7246
    Email: CancerClinicalTrials@orlandohealth.com

    Saint Petersburg

    All Children's Hospital

    Gregory A Hale
    Ph: 727-767-2423
    Email: HamblinF@allkids.org

    Georgia
    Atlanta

    AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

    Todd M Cooper
    Ph: 404-785-1112

    Illinois
    Chicago

    Ann and Robert H. Lurie Children's Hospital of Chicago

    Joanna L Weinstein
    Ph: 773-880-4562

    University of Chicago Cancer Research Center

    Tara O Henderson
    Ph: 773-834-7424

    University of Illinois Cancer Center

    Mary L Schmidt
    Ph: 312-355-3046

    Peoria

    Saint Jude Midwest Affiliate

    Karen S Fernandez
    Ph: 309-655-3258

    Springfield

    Simmons Cooper Cancer Institute

    Gregory P Brandt
    Ph: 217-545-7929

    Indiana
    Indianapolis

    Riley's Children Cancer Center at Riley Hospital for Children

    James M Croop
    Ph: 888-823-5923
    Email: ctsucontact@westat.com

    Kentucky
    Lexington

    University of Kentucky Chandler Medical Center

    Lars M Wagner
    Ph: 859-257-3379

    Louisiana
    New Orleans

    Ochsner Cancer Institute at Ochsner Clinic Foundation

    Craig Lotterman
    Ph: 888-562-4763

    Maine
    Scarborough

    Maine Children's Cancer Program at Barbara Bush Children's Hospital

    Aaron R Weiss
    Ph: 207-396-8090
    Email: wrighd@mmc.org

    Maryland
    Baltimore

    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Allen R. Chen
    Ph: 410-955-8804
    Email: jhcccro@jhmi.edu

    Massachusetts
    Boston

    Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

    Carlos Rodriguez-Galindo
    Ph: 866-790-4500

    Massachusetts General Hospital

    Howard J Weinstein
    Ph: 877-726-5130

    Michigan
    Detroit

    Van Elslander Cancer Center at St. John Hospital and Medical Center

    Hadi Sawaf
    Ph: 313-343-3166

    Minnesota
    Minneapolis

    Masonic Cancer Center at University of Minnesota

    Emily G Greengard
    Ph: 612-624-2620

    Mississippi
    Jackson

    University of Mississippi Cancer Clinic

    Anderson (Andy) B Collier
    Ph: 601-815-6700

    Missouri
    Saint Louis

    Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    Robert J Hayashi
    Ph: 800-600-3606
    Email: info@siteman.wustl.edu

    New Jersey
    Hackensack

    Hackensack University Medical Center Cancer Center

    Burton E Appel
    Ph: 201-996-2879

    New Brunswick

    Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

    Richard A Drachtman
    Ph: 732-235-8675

    Paterson

    St. Joseph's Hospital and Medical Center

    Mary A Bonilla
    Ph: 973-754-2909

    New York
    Albany

    Albany Medical Center Hospital

    Vikramjit S Kanwar
    Ph: 518-262-3368

    Bronx

    Montefiore Medical Center

    Peter D Cole
    Ph: 718-904-2730
    Email: aecc@aecom.yu.edu

    New York

    Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

    Alice Lee
    Ph: 212-305-8615

    Rochester

    James P. Wilmot Cancer Center at University of Rochester Medical Center

    Jeffrey R Andolina
    Ph: 585-275-5830

    Syracuse

    SUNY Upstate Medical University Hospital

    Karol H Kerr
    Ph: 315-464-5476

    North Carolina
    Winston-Salem

    Wake Forest University Comprehensive Cancer Center

    Sharon M Castellino
    Ph: 336-713-6771

    North Dakota
    Fargo

    Roger Maris Cancer Center at MeritCare Hospital

    Samuel O Anim
    Ph: 701-234-6161

    Ohio
    Cincinnati

    Cincinnati Children's Hospital Medical Center

    John P Perentesis
    Ph: 513-636-2799

    Columbus

    Nationwide Children's Hospital

    Mark A Ranalli
    Ph: 614-722-2708

    Oklahoma
    Oklahoma City

    Stephenson Cancer Center at the University of Oklahoma

    Rene Y McNall-Knapp
    Ph: 405-271-4272
    Email: julie-traylor@ouhsc.edu

    Oregon
    Portland

    Knight Cancer Institute at Oregon Health and Science University

    Susan J Lindemulder
    Ph: 503-494-1080
    Email: trials@ohsu.edu

    Pennsylvania
    Hershey

    Penn State Children's Hospital

    Lisa M McGregor
    Ph: 717-531-6012

    Philadelphia

    Children's Hospital of Philadelphia

    Leslie S Kersun
    Ph: 215-590-2810

    South Dakota
    Sioux Falls

    Sanford Cancer Center at Sanford USD Medical Center

    Kayelyn J Wagner
    Ph: 605-328-1367

    Tennessee
    Memphis

    St. Jude Children's Research Hospital

    Monika Metzger
    Ph: 866-278-5833
    Email: info@stjude.org

    Texas
    Austin

    Dell Children's Medical Center of Central Texas

    Amy C Fowler
    Ph: 214-648-7097

    Dallas

    Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Martha M Stegner
    Ph: 214-648-7097

    Houston

    Dan L. Duncan Cancer Center at Baylor College of Medicine

    Terzah M Horton
    Ph: 713-798-1354
    Email: burton@bcm.edu

    Virginia
    Norfolk

    Children's Hospital of The King's Daughters

    Eric J Lowe
    Ph: 757-668-7243

    Richmond

    Virginia Commonwealth University Massey Cancer Center

    Gita V Massey
    Ph: 804-628-1939

    Washington
    Seattle

    Children's Hospital and Regional Medical Center - Seattle

    Douglas S Hawkins
    Ph: 866-987-2000

    Spokane

    Providence Cancer Center at Sacred Heart Medical Center

    Judy L Felgenhauer
    Ph: 800-228-6618
    Email: HopeBeginsHere@providence.org

    Wisconsin
    Milwaukee

    Midwest Children's Cancer Center at Children's Hospital of Wisconsin

    Michael E Kelly
    Ph: 414-805-4380

    Canada

    Quebec
    Montreal

    Hopital Sainte Justine

    Yvan Samson
    Ph: 514-345-4931

    Link to the current ClinicalTrials.gov record.
    NLM Identifier NCT01780662
    ClinicalTrials.gov processed this data on May 18, 2015

    Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.