Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01780662
Other study ID # NCI-2013-00107
Secondary ID NCI-2013-00107AH
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date January 31, 2013
Est. completion date September 30, 2021

Study information

Verified date October 2021
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of brentuximab vedotin in combination with gemcitabine 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 15 more 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.


Recruitment information / eligibility

Status Completed
Enrollment 46
Est. completion date September 30, 2021
Est. primary completion date September 30, 2017
Accepts healthy volunteers No
Gender All
Age group 13 Months to 30 Years
Eligibility 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 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Brentuximab Vedotin
Given IV
Gemcitabine Hydrochloride
Given IV

Locations

Country Name City State
Canada McMaster Children's Hospital at Hamilton Health Sciences Hamilton Ontario
Canada Kingston Health Sciences Centre Kingston Ontario
Canada Children's Hospital London Ontario
Canada Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec
Canada The Montreal Children's Hospital of the MUHC Montreal Quebec
Canada Centre Hospitalier Universitaire de Quebec Quebec
Canada Hospital for Sick Children Toronto Ontario
United States Children's Hospital Medical Center of Akron Akron Ohio
United States Albany Medical Center Albany New York
United States C S Mott Children's Hospital Ann Arbor Michigan
United States Children's Healthcare of Atlanta - Egleston Atlanta Georgia
United States Children's Hospital Colorado Aurora Colorado
United States Dell Children's Medical Center of Central Texas Austin Texas
United States Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland
United States Sinai Hospital of Baltimore Baltimore Maryland
United States Children's Hospital of Alabama Birmingham Alabama
United States Saint Luke's Cancer Institute - Boise Boise Idaho
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Cancer Center Boston Massachusetts
United States Montefiore Medical Center - Moses Campus Bronx New York
United States Roswell Park Cancer Institute Buffalo New York
United States Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina
United States Lurie Children's Hospital-Chicago Chicago Illinois
United States University of Chicago Comprehensive Cancer Center Chicago Illinois
United States University of Illinois Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Cleveland Clinic Foundation Cleveland Ohio
United States Rainbow Babies and Childrens Hospital Cleveland Ohio
United States Nationwide Children's Hospital Columbus Ohio
United States Driscoll Children's Hospital Corpus Christi Texas
United States UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas
United States Dayton Children's Hospital Dayton Ohio
United States Blank Children's Hospital Des Moines Iowa
United States Ascension Saint John Hospital Detroit Michigan
United States Kaiser Permanente Downey Medical Center Downey California
United States Sanford Broadway Medical Center Fargo North Dakota
United States Golisano Children's Hospital of Southwest Florida Fort Myers Florida
United States Cook Children's Medical Center Fort Worth Texas
United States University of Florida Health Science Center - Gainesville Gainesville Florida
United States BI-LO Charities Children's Cancer Center Greenville South Carolina
United States Hackensack University Medical Center Hackensack New Jersey
United States Penn State Children's Hospital Hershey Pennsylvania
United States Memorial Regional Hospital/Joe DiMaggio Children's Hospital Hollywood Florida
United States Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas
United States Riley Hospital for Children Indianapolis Indiana
United States University of Mississippi Medical Center Jackson Mississippi
United States Nemours Children's Clinic-Jacksonville Jacksonville Florida
United States Bronson Methodist Hospital Kalamazoo Michigan
United States Children's Mercy Hospitals and Clinics Kansas City Missouri
United States East Tennessee Childrens Hospital Knoxville Tennessee
United States Alliance for Childhood Diseases/Cure 4 the Kids Foundation Las Vegas Nevada
United States Sunrise Hospital and Medical Center Las Vegas Nevada
United States Dartmouth Hitchcock Medical Center Lebanon New Hampshire
United States University of Kentucky/Markey Cancer Center Lexington Kentucky
United States Loma Linda University Medical Center Loma Linda California
United States Children's Hospital Los Angeles Los Angeles California
United States Valley Children's Hospital Madera California
United States University of Wisconsin Hospital and Clinics Madison Wisconsin
United States Saint Jude Children's Research Hospital Memphis Tennessee
United States Nicklaus Children's Hospital Miami Florida
United States Children's Hospital of Wisconsin Milwaukee Wisconsin
United States University of Minnesota/Masonic Cancer Center Minneapolis Minnesota
United States West Virginia University Healthcare Morgantown West Virginia
United States Morristown Medical Center Morristown New Jersey
United States Vanderbilt University/Ingram Cancer Center Nashville Tennessee
United States Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital New Brunswick New Jersey
United States Yale University New Haven Connecticut
United States Ochsner Medical Center Jefferson New Orleans Louisiana
United States NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center New York New York
United States NYP/Weill Cornell Medical Center New York New York
United States Newark Beth Israel Medical Center Newark New Jersey
United States Children's Hospital of The King's Daughters Norfolk Virginia
United States UCSF Benioff Children's Hospital Oakland Oakland California
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Children's Hospital of Orange County Orange California
United States AdventHealth Orlando Orlando Florida
United States Arnold Palmer Hospital for Children Orlando Florida
United States Nemours Children's Hospital Orlando Florida
United States Lucile Packard Children's Hospital Stanford University Palo Alto California
United States Saint Joseph's Regional Medical Center Paterson New Jersey
United States Nemours Children's Clinic - Pensacola Pensacola Florida
United States Saint Jude Midwest Affiliate Peoria Illinois
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Saint Christopher's Hospital for Children Philadelphia Pennsylvania
United States Phoenix Childrens Hospital Phoenix Arizona
United States Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania
United States Legacy Emanuel Children's Hospital Portland Oregon
United States Oregon Health and Science University Portland Oregon
United States Virginia Commonwealth University/Massey Cancer Center Richmond Virginia
United States University of Rochester Rochester New York
United States Sutter Medical Center Sacramento Sacramento California
United States University of California Davis Comprehensive Cancer Center Sacramento California
United States Washington University School of Medicine Saint Louis Missouri
United States Johns Hopkins All Children's Hospital Saint Petersburg Florida
United States Primary Children's Hospital Salt Lake City Utah
United States Children's Hospital of San Antonio San Antonio Texas
United States Methodist Children's Hospital of South Texas San Antonio Texas
United States University of Texas Health Science Center at San Antonio San Antonio Texas
United States Rady Children's Hospital - San Diego San Diego California
United States UCSF Medical Center-Mission Bay San Francisco California
United States Memorial Health University Medical Center Savannah Georgia
United States Maine Children's Cancer Program Scarborough Maine
United States Seattle Children's Hospital Seattle Washington
United States Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota
United States Providence Sacred Heart Medical Center and Children's Hospital Spokane Washington
United States Baystate Medical Center Springfield Massachusetts
United States Southern Illinois University School of Medicine Springfield Illinois
United States Stony Brook University Medical Center Stony Brook New York
United States State University of New York Upstate Medical University Syracuse New York
United States Madigan Army Medical Center Tacoma Washington
United States New York Medical College Valhalla New York
United States Children's National Medical Center Washington District of Columbia
United States MedStar Georgetown University Hospital Washington District of Columbia
United States Saint Mary's Hospital West Palm Beach Florida
United States Alfred I duPont Hospital for Children Wilmington Delaware
United States Wake Forest University Health Sciences Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum Tolerated Dose (MTD) for Brentuximab Vedotin MTD was determined as the maximum dose at which fewer than one-third of patients experience Dose Limiting Toxicities (DLT) as assessed by National Cancer Institute (NCI) CTCAE v 4.0 during Cycle 1 of therapy. Gemcitabine was administered on days 1 and 8 of a 21 day cycle at a fixed dose. Brentuximab vedotin was investigated at a starting dose of 1.4 mg/kg administered on day 1 and escalated if tolerated. During cycle 1 of protocol therapy (21 days)
Primary Adverse Events Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 The number of eligible patients assigned to receive brentuximab vedotin in combination with gemcitabine that experienced CTC Version 4, grade 3 or higher adverse events during Phase 1 and Phase 2. 13 months from first dose
Primary The Number of Patients With Relapsed or Refractory HL Who Achieved Complete Response (CR) The number of patients who experienced complete Response (CR) within the first four cycles. By modern response criteria, those with partial response (PR) or stable disease with all target lesions with Deauville scores <=3 after cycle 4 are also considered as CR. Patients were assessed after treatment with four cycles of gemcitabine with brentuximab vedotin. CR was only reported for Dose level 2 across both phases of study. After 4 cycles (21 days per cycle) of protocol therapy
Secondary The Number of Patients Who Had Disease Response Assessed by Deauville Scales Among Those in Phase I With Dose Level 2. The Deauville five-point scale was used to assess the number of participants with complete response (CR) and partial response (PR). A lower score indicates a better outcome. Scores of 1-3 represent CR and 4-5 represent PR. Up to 13 months from first dose
Secondary Percentage of Patients Who Achieved Overall Response (OR) as Measured by Complete Response (CR) and Partial Response (PR) The percentage of patients who experienced complete Response (CR) within the first four cycles.By modern response criteria, those with partial response (PR) or stable disease with all target lesions with Deauville scores <=3 after cycle 4 are also considered as CR. Patients were assessed after treatment with four cycles of gemcitabine with brentuximab vedotin. CR was only reported for Dose level 2 across both phases of study. After 4 cycles (21 days per cycle) of protocol therapy
Secondary The Number of Patients Who Had Successful Peripheral Blood Stem Cell (PBSC) Collection Successful PBSC collection was defined as a collection of more than 2x10^6 CD34 positive cells. From 1 to 5 cycles
Secondary Plasma Level of Thymus and Activation-Regulated Chemokine (TARC) Limit to 41 evaluable patients who received dose 1.8 mg/kg From baseline to time prior to cycle 2
Secondary Correlation Between Micro Ribonucleic Acid (miRNA) and Disease Response to Protocol Treatment Limit to 41 evaluable patients who received dose 1.8 mg/kg From the end of first dose to the end of last dose (Up to 13 Months)
Secondary Number of Patients With FcyRIIIa-158 V/F (Valine/Phenylalanine) Polymorphism Among patients who received 1.8mg/kg dose, the frequency of the Fc?RIIIa-158 V/F polymorphism are described. From the end of first dose to the end of last dose (Up to 13 Months)
See also
  Status Clinical Trial Phase
Completed NCT02168140 - CPI-613 and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma Phase 1
Completed NCT01902160 - Temsirolimus and Brentuximab Vedotin in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma Phase 1
Completed NCT01427881 - Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies Phase 2
Completed NCT01165112 - Bendamustine Hydrochloride, Rituximab, Etoposide, and Carboplatin in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma or Hodgkin Lymphoma Phase 1/Phase 2
Completed NCT01233921 - Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer N/A
Completed NCT00132028 - Vorinostat in Treating Patients With Relapsed or Refractory Advanced Hodgkin's Lymphoma Phase 2
Completed NCT00078858 - Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant Phase 1/Phase 2
Completed NCT00005803 - Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma Phase 1/Phase 2
Terminated NCT01678443 - Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies Phase 1
Completed NCT01588015 - Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant Phase 1
Completed NCT02240719 - Everolimus and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory Hematologic Cancer Phase 1
Completed NCT00608361 - Dasatinib in Treating Patients With Solid Tumors or Lymphomas That Are Metastatic or Cannot Be Removed By Surgery Phase 1
Terminated NCT00288067 - Fenretinide and Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma Phase 1/Phase 2
Completed NCT00098891 - MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas Phase 1
Completed NCT00004241 - 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma Phase 1
Completed NCT01460940 - A Phase II Trial of Panobinostat and Lenalidomide in Patients With Relapsed or Refractory Hodgkin's Lymphoma Phase 2
Active, not recruiting NCT01476839 - Radiolabeled Monoclonal Antibody Therapy and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With Primary Refractory or Relapsed Hodgkin Lymphoma Phase 1
Completed NCT01748721 - MORAb-004 in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma Phase 1
Terminated NCT00101244 - SB-715992 in Treating Patients With Metastatic or Unresectable Solid Tumors or Hodgkin's or Non-Hodgkin's Lymphoma Phase 1
Terminated NCT00096005 - Tanespimycin and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas Phase 1