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

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase II, Phase IBiomarker/Laboratory analysis, Treatment13 to 30AHOD1221
NCI-2013-00107, COG-AHOD1221, 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:

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

Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4) resulting from prior therapy must be < grade 2

Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled

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

No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry > 92% while breathing room air

Serum albumin >= 2 g/dL

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

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)

Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 OR

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

Platelet count >= 75,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)

Peripheral absolute neutrophil count (ANC) >= 750/uL

PART B: FOR PATIENTS WITHOUT KNOWN BONE MARROW INVOLVEMENT

Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)

Peripheral absolute neutrophil count (ANC) >= 1000/uL

PART A: FOR PATIENTS WITH KNOWN BONE MARROW INVOLVEMENT (Completed as of Amendment 4)

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

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 a life expectancy of >= 8 weeks (>= 56 days)

Patients must have measurable disease, documented by clinical and radiographic criteria

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

Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age

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)

Exclusion Criteria:

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

Patients with known hypersensitivity to Escherichia coli (E.coli)-derived proteins, filgrastim, or any component of filgrastim 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 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 who have an uncontrolled infection are not eligible

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

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

All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

All patients and/or their parents or legal guardians must sign a written informed consent

Patients who have received a prior solid organ transplantation are not eligible

Patients known to be positive for human immunodeficiency virus (HIV) are not eligible

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

National Cancer Institute

  • National Cancer Institute
Peter David Cole, Principal Investigator

Trial Sites

U.S.A.

Alabama
Birmingham

Children's Hospital of Alabama

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

Alyssa Terry Reddy
Principal Investigator

California
Downey

Southern California Permanente Medical Group

Robert Michael Cooper
Ph: 626-564-3455

Robert Michael Cooper
Principal Investigator

Loma Linda

Loma Linda University Medical Center

Albert Kheradpour
Ph: 909-558-3375

Albert Kheradpour
Principal Investigator

Los Angeles

Children's Hospital Los Angeles

Leo Mascarenhas
Ph: 323-361-4110

Leo Mascarenhas
Principal Investigator

Madera

Children's Hospital Central California

Vonda Lee Crouse
Ph: 866-353-5437

Vonda Lee Crouse
Principal Investigator

Oakland

Children's Hospital and Research Center at Oakland

Carla Barbara Golden
Ph: 510-450-7600

Carla Barbara Golden
Principal Investigator

Orange

Childrens Hospital of Orange County

Violet Shen
Ph: 714-997-3000

Violet Shen
Principal Investigator

Palo Alto

Lucile Packard Children's Hospital Stanford University

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

Neyssa Maria Marina
Principal Investigator

Sacramento

Sutter General Hospital

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

Yung Soon Yim
Principal Investigator

University of California Davis Comprehensive Cancer Center

Jay Michael S. Balagtas
Ph: 916-734-3089

Jay Michael S. Balagtas
Principal Investigator

San Diego

Rady Children's Hospital - San Diego

William D. Roberts
Ph: 858-966-5934

William D. Roberts
Principal Investigator

San Francisco

UCSF Medical Center-Mission Bay

Michelle Lynn Hermiston
Ph: 877-827-3222

Michelle Lynn Hermiston
Principal Investigator

Connecticut
New Haven

Yale University

Nina Singh Kadan-Lottick
Ph: 203-785-5702

Nina Singh Kadan-Lottick
Principal Investigator

Delaware
Wilmington

Alfred I duPont Hospital for Children

Ramamoorthy Nagasubramanian
Ph: 407-650-7150

Ramamoorthy Nagasubramanian
Principal Investigator

District of Columbia
Washington

Children's National Medical Center

Jeffrey Stuart Dome
Ph: 202-884-2549

Jeffrey Stuart Dome
Principal Investigator

MedStar Georgetown University Hospital

Aziza Tahir Shad
Ph: 202-444-0381

Aziza Tahir Shad
Principal Investigator

Florida
Hollywood

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Iftikhar Hanif
Ph: 954-265-2234

Iftikhar Hanif
Principal Investigator

Jacksonville

Nemours Children's Clinic-Jacksonville

Ramamoorthy Nagasubramanian
Ph: 407-650-7150

Ramamoorthy Nagasubramanian
Principal Investigator

Orlando

Arnold Palmer Hospital for Children

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

Vincent Ferdinando Giusti
Principal Investigator

Nemours Children's Hospital

Ramamoorthy Nagasubramanian
Ph: 407-650-7150

Ramamoorthy Nagasubramanian
Principal Investigator

Pensacola

Nemours Children's Clinic - Pensacola

Ramamoorthy Nagasubramanian
Ph: 407-650-7150

Ramamoorthy Nagasubramanian
Principal Investigator

Saint Petersburg

All Children's Hospital

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

Gregory Alan Hale
Principal Investigator

Georgia
Atlanta

Children's Healthcare of Atlanta - Egleston

Glen Lew
Ph: 404-785-1112

Glen Lew
Principal Investigator

Illinois
Chicago

Lurie Children's Hospital-Chicago

Joanna Lynn Weinstein
Ph: 773-880-4562

Joanna Lynn Weinstein
Principal Investigator

University of Chicago Comprehensive Cancer Center

Tara Olive Henderson
Ph: 773-834-7424

Tara Olive Henderson
Principal Investigator

University of Illinois

Mary Lou Schmidt
Ph: 312-355-3046

Mary Lou Schmidt
Principal Investigator

Peoria

Saint Jude Midwest Affiliate

Karen Sofia Fernandez
Ph: 309-655-3258

Karen Sofia Fernandez
Principal Investigator

Springfield

Southern Illinois University School of Medicine

Gregory P. Brandt
Ph: 217-545-7929

Gregory P. Brandt
Principal Investigator

Indiana
Indianapolis

Riley Hospital for Children

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

James Merrill Croop
Principal Investigator

Kentucky
Lexington

University of Kentucky/Markey Cancer Center

Lars Martin Wagner
Ph: 859-257-3379

Lars Martin Wagner
Principal Investigator

Louisiana
New Orleans

Ochsner Medical Center Jefferson

Craig Lotterman
Ph: 888-562-4763

Craig Lotterman
Principal Investigator

Maine
Scarborough

Maine Children's Cancer Program

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

Aaron Robert Weiss
Principal Investigator

Maryland
Baltimore

Johns Hopkins University/Sidney Kimmel Cancer Center

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

Allen R. Chen
Principal Investigator

Massachusetts
Boston

Dana-Farber Cancer Institute

Carlos Rodriguez-Galindo
Ph: 877-442-3324

Carlos Rodriguez-Galindo
Principal Investigator

Massachusetts General Hospital Cancer Center

Howard Jeffrey Weinstein
Ph: 877-726-5130

Howard Jeffrey Weinstein
Principal Investigator

Springfield

Baystate Medical Center

Joanna G. Luty
Ph: 413-794-3565
Email: tamara.wrenn@baystatehealth.org

Joanna G. Luty
Principal Investigator

Michigan
Detroit

Saint John Hospital and Medical Center

Hadi Sawaf
Ph: 313-343-3166

Hadi Sawaf
Principal Investigator

Kalamazoo

Bronson Methodist Hospital

Katharina Elisabeth Elliott
Ph: 800-227-2345

Katharina Elisabeth Elliott
Principal Investigator

Minnesota
Minneapolis

University of Minnesota Medical Center-Fairview

Emily G. Greengard
Ph: 612-624-2620

Emily G. Greengard
Principal Investigator

Mississippi
Jackson

University of Mississippi Medical Center

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

Anderson (Andy) Burton Collier
Principal Investigator

Missouri
Saint Louis

Washington University School of Medicine

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

Robert J. Hayashi
Principal Investigator

New Jersey
Hackensack

Hackensack University Medical Center

Burton Eliot Appel
Ph: 201-996-2879

Burton Eliot Appel
Principal Investigator

New Brunswick

UMDNJ - Robert Wood Johnson University Hospital

Richard A. Drachtman
Ph: 732-235-8675

Richard A. Drachtman
Principal Investigator

Paterson

Saint Joseph's Regional Medical Center

Mary Ann Bonilla
Ph: 973-754-2909

Mary Ann Bonilla
Principal Investigator

New York
Albany

Albany Medical Center

Vikramjit Singh Kanwar
Ph: 518-262-3368

Vikramjit Singh Kanwar
Principal Investigator

Bronx

Montefiore Medical Center - Moses Campus

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

Peter David Cole
Principal Investigator

New York

Columbia University Medical Center

Alice Lee
Ph: 212-305-8615

Alice Lee
Principal Investigator

Rochester

University of Rochester

Jeffrey Robert Andolina
Ph: 585-275-5830

Jeffrey Robert Andolina
Principal Investigator

Syracuse

State University of New York Upstate Medical University

Karol Hicks Kerr
Ph: 315-464-5476

Karol Hicks Kerr
Principal Investigator

North Carolina
Charlotte

Carolinas Medical Center/Levine Cancer Institute

Joel A. Kaplan
Ph: 704-355-2884

Joel A. Kaplan
Principal Investigator

Winston-Salem

Wake Forest University Health Sciences

Sharon M. Castellino
Ph: 336-713-6771

Sharon M. Castellino
Principal Investigator

North Dakota
Fargo

Sanford Medical Center-Fargo

Samuel Odame Anim
Ph: 701-234-6161

Samuel Odame Anim
Principal Investigator

Ohio
Cincinnati

Cincinnati Children's Hospital Medical Center

John Peter Perentesis
Ph: 513-636-2799

John Peter Perentesis
Principal Investigator

Columbus

Nationwide Children's Hospital

Mark Anthony Ranalli
Ph: 614-722-2708

Mark Anthony Ranalli
Principal Investigator

Oklahoma
Oklahoma City

University of Oklahoma Health Sciences Center

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

Rene Yvonne McNall-Knapp
Principal Investigator

Oregon
Portland

Oregon Health and Science University

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

Susan Joy Lindemulder
Principal Investigator

Pennsylvania
Hershey

Penn State Hershey Children's Hospital

Lisa MacNabb McGregor
Ph: 717-531-6012

Lisa MacNabb McGregor
Principal Investigator

Philadelphia

Children's Hospital of Philadelphia

Leslie S. Kersun
Ph: 215-590-2810

Leslie S. Kersun
Principal Investigator

South Dakota
Sioux Falls

Sanford USD Medical Center - Sioux Falls

Kayelyn Jean Wagner
Ph: 605-328-1367

Kayelyn Jean Wagner
Principal Investigator

Tennessee
Knoxville

East Tennessee Childrens Hospital

Ray C. Pais
Ph: 865-541-8266

Ray C. Pais
Principal Investigator

Memphis

St. Jude Children's Research Hospital

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

Monika Metzger
Principal Investigator

Nashville

Vanderbilt University/Ingram Cancer Center

Kristen Marie Snyder
Ph: 800-811-8480

Kristen Marie Snyder
Principal Investigator

Texas
Austin

Dell Children's Medical Center of Central Texas

Amy Catherine Fowler
Ph: 214-648-7097

Amy Catherine Fowler
Principal Investigator

Dallas

UT Southwestern/Simmons Cancer Center-Dallas

Martha Marie Stegner
Ph: 214-648-7097

Martha Marie Stegner
Principal Investigator

Houston

Baylor College of Medicine

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

Terzah M. Horton
Principal Investigator

San Antonio

Methodist Children's Hospital of South Texas

Jaime Estrada
Ph: 210-575-7000

Jaime Estrada
Principal Investigator

Utah
Salt Lake City

Primary Children's Hospital

Phillip Evan Barnette
Ph: 801-585-5270

Phillip Evan Barnette
Principal Investigator

Virginia
Norfolk

Childrens Hospital-King's Daughters

Eric Jeffrey Lowe
Ph: 757-668-7243

Eric Jeffrey Lowe
Principal Investigator

Richmond

Virginia Commonwealth University/Massey Cancer Center

Gita Vasers Massey
Ph: 804-628-1939

Gita Vasers Massey
Principal Investigator

Washington
Seattle

Seattle Children's Hospital

Douglas S. Hawkins
Ph: 866-987-2000

Douglas S. Hawkins
Principal Investigator

Spokane

Providence Sacred Heart Medical Center and Children's Hospital

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

Judy L. Felgenhauer
Principal Investigator

West Virginia
Morgantown

West Virginia University Healthcare

Stephan R. Paul
Ph: 304-293-2745
Email: sfilburn@hsc.wvu.edu

Stephan R. Paul
Principal Investigator

Wisconsin
Madison

University of Wisconsin Hospital and Clinics

Kenneth Brian DeSantes
Ph: 608-262-5223

Kenneth Brian DeSantes
Principal Investigator

Milwaukee

Midwest Children's Cancer Center

Michael Edward Kelly
Ph: 414-805-4380

Michael Edward Kelly
Principal Investigator

Canada

Ontario
Hamilton

McMaster Children's Hospital at Hamilton Health Sciences

Carol Portwine
Ph: 905-521-2100ext74595

Carol Portwine
Principal Investigator

Quebec
Montreal

Centre Hospitalier Universitaire Sainte-Justine

Yvan Samson
Ph: 514-345-4931

Yvan Samson
Principal Investigator

Quebec

Centre Hospitalier Universitaire de Quebec

Bruno Michon
Ph: 418-525-4444

Bruno Michon
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01780662

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.