Recruitment

Recruitment Status
Active, not recruiting
Estimated Enrollment
75

Inclusion Criteria

Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 OR
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
...
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 OR
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
Serum albumin >= 2 g/dL
=< 1.2 mg/dL (for 10 to < 13 years of 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)
=< 1.4 mg/dL (for females >= 13 years of age)
PART B: FOR PATIENTS WITHOUT KNOWN BONE MARROW INVOLVEMENT
Platelet count >= 75,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
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
=< 1.7 mg/dL (for males >= 16 years of age)
=< 0.6 mg/dL (for 1 to < 2 years of age)
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
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
=< 1.5 mg/dL (for males 13 to < 16 years of age)
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
Primary refractory disease (i.e. no prior CR)
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
Very early relapse (< 6 months from the end of initial therapy, including chemotherapy ± radiation)
Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4) resulting from prior therapy must be < grade 2
Peripheral absolute neutrophil count (ANC) >= 1000/uL
Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
PART A: FOR PATIENTS WITH KNOWN BONE MARROW INVOLVEMENT (Completed as of Amendment 4)
Peripheral absolute neutrophil count (ANC) >= 750/uL
No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry > 92% while breathing room air
Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
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
=< 1.0 mg/dL (for 6 to < 10 years of age)
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
At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
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
Patients must have measurable disease, documented by clinical and radiographic criteria
Patients with prior autologous or allogeneic stem cell transplant (SCT) are excluded from this study
Advanced stage (III or IV) at diagnosis who relapse less than one year from the end of initial therapy
Patients must have a life expectancy of >= 8 weeks (>= 56 days)
At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
=< 0.8 mg/dL (for 2 to < 6 years of age)
Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)

Exclusion Criteria

Patients with known hypersensitivity to Escherichia coli (E.coli)-derived proteins, filgrastim, or any component of filgrastim 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
Patients who are currently receiving other anti-cancer agents are not eligible
...
Patients with known hypersensitivity to Escherichia coli (E.coli)-derived proteins, filgrastim, or any component of filgrastim 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
Patients who are currently receiving other anti-cancer agents are not eligible
Patients who have an uncontrolled infection are not eligible
All patients and/or their parents or legal guardians must sign a written informed consent
Patients with prior exposure to brentuximab vedotin are not eligible; NOTE: prior exposure to gemcitabine is NOT an exclusion criterion
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
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 in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
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 have undergone prior autologous or allogeneic SCT are not eligible
Patients known to be positive for human immunodeficiency virus (HIV) 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

Summary

Conditions
  • Recurrent Adult Hodgkin Lymphoma
  • Recurrent Childhood Hodgkin Lymphoma
  • Refractory Childhood Hodgkin Lymphoma
Type
Interventional
Phase
Phase 1 & Phase 2
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Younger than 1330 years
Gender
Both males and females

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 o...

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.

Inclusion Criteria

Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 OR
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
...
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 OR
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
Serum albumin >= 2 g/dL
=< 1.2 mg/dL (for 10 to < 13 years of 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)
=< 1.4 mg/dL (for females >= 13 years of age)
PART B: FOR PATIENTS WITHOUT KNOWN BONE MARROW INVOLVEMENT
Platelet count >= 75,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
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
=< 1.7 mg/dL (for males >= 16 years of age)
=< 0.6 mg/dL (for 1 to < 2 years of age)
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
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
=< 1.5 mg/dL (for males 13 to < 16 years of age)
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
Primary refractory disease (i.e. no prior CR)
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
Very early relapse (< 6 months from the end of initial therapy, including chemotherapy ± radiation)
Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4) resulting from prior therapy must be < grade 2
Peripheral absolute neutrophil count (ANC) >= 1000/uL
Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
PART A: FOR PATIENTS WITH KNOWN BONE MARROW INVOLVEMENT (Completed as of Amendment 4)
Peripheral absolute neutrophil count (ANC) >= 750/uL
No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry > 92% while breathing room air
Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
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
=< 1.0 mg/dL (for 6 to < 10 years of age)
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
At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
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
Patients must have measurable disease, documented by clinical and radiographic criteria
Patients with prior autologous or allogeneic stem cell transplant (SCT) are excluded from this study
Advanced stage (III or IV) at diagnosis who relapse less than one year from the end of initial therapy
Patients must have a life expectancy of >= 8 weeks (>= 56 days)
At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
=< 0.8 mg/dL (for 2 to < 6 years of age)
Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)

Exclusion Criteria

Patients with known hypersensitivity to Escherichia coli (E.coli)-derived proteins, filgrastim, or any component of filgrastim 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
Patients who are currently receiving other anti-cancer agents are not eligible
...
Patients with known hypersensitivity to Escherichia coli (E.coli)-derived proteins, filgrastim, or any component of filgrastim 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
Patients who are currently receiving other anti-cancer agents are not eligible
Patients who have an uncontrolled infection are not eligible
All patients and/or their parents or legal guardians must sign a written informed consent
Patients with prior exposure to brentuximab vedotin are not eligible; NOTE: prior exposure to gemcitabine is NOT an exclusion criterion
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
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 in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
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 have undergone prior autologous or allogeneic SCT are not eligible
Patients known to be positive for human immunodeficiency virus (HIV) 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

Locations

Indianapolis, Indiana, 46202
Loma Linda, California, 92354
Toronto, Ontario, M5G 1X8
Palo Alto, California, 94304
Seattle, Washington, 98105
...
Indianapolis, Indiana, 46202
Loma Linda, California, 92354
Toronto, Ontario, M5G 1X8
Palo Alto, California, 94304
Seattle, Washington, 98105
Cleveland, Ohio, 44106
Kalamazoo, Michigan, 49007
Norfolk, Virginia, 23507
Pensacola, Florida, 32504
Richmond, Virginia, 23298
Birmingham, Alabama, 35233
Cleveland, Ohio, 44195
Spokane, Washington, 99204
Orlando, Florida, 32803
Akron, Ohio, 44308
Washington, District of Columbia, 20007
Kansas City, Missouri, 64108
New York, New York, 10065
Philadelphia, Pennsylvania, 19134
Washington, District of Columbia, 20010
Saint Petersburg, Florida, 33701
Minneapolis, Minnesota, 55455
Ann Arbor, Michigan, 48109
Detroit, Michigan, 48236
Morristown, New Jersey, 07960
Valhalla, New York, 10595
Boise, Idaho, 83712
Charlotte, North Carolina, 28203
West Palm Beach, Florida, 33407
Paterson, New Jersey, 07503
Scarborough, Maine, 04074
Jacksonville, Florida, 32207
Des Moines, Iowa, 50309
Chicago, Illinois, 60611
Baltimore, Maryland, 21287
Milwaukee, Wisconsin, 53226
Springfield, Massachusetts, 01199
Wilmington, Delaware, 19803
Sacramento, California, 95817
Cincinnati, Ohio, 45229
Syracuse, New York, 13210
Hershey, Pennsylvania, 17033
Morgantown, West Virginia, 26506
Tacoma, Washington, 98431
Greenville, South Carolina, 29605
Jackson, Mississippi, 39216
Baltimore, Maryland, 21215
Winston-Salem, North Carolina, 27157
Hamilton, Ontario, L8N 3Z5
Sioux Falls, South Dakota, 57117-5134
Albany, New York, 12208
Philadelphia, Pennsylvania, 19104
Montreal, Quebec, H3T 1C5
Bronx, New York, 10467
San Antonio, Texas, 78207
Hackensack, New Jersey, 07601
Portland, Oregon, 97227
Knoxville, Tennessee, 37916
Phoenix, Arizona, 85016
Lexington, Kentucky, 40536
Fort Worth, Texas, 76104
Las Vegas, Nevada, 89109
Peoria, Illinois, 61637
Houston, Texas, 77030
Buffalo, New York, 14263
Aurora, Colorado, 80045
Pittsburgh, Pennsylvania, 15224
Boston, Massachusetts, 02215
Los Angeles, California, 90027
Saint Louis, Missouri, 63110
Austin, Texas, 78723
Kingston, Ontario, K7L 2V7
Downey, California, 90242
Memphis, Tennessee, 38105
New Orleans, Louisiana, 70121
Sacramento, California, 95816
Montreal, Quebec, H3H 1P3
Orange, California, 92868
Orlando, Florida, 32806
Fargo, North Dakota, 58122
Dallas, Texas, 75390
Madison, Wisconsin, 53792
San Francisco, California, 94158
Boston, Massachusetts, 02114
Columbus, Ohio, 43205
Gainesville, Florida, 32610
Portland, Oregon, 97239
New Brunswick, New Jersey, 08903
San Antonio, Texas, 78229
Oklahoma City, Oklahoma, 73104
Dayton, Ohio, 45404
Nashville, Tennessee, 37232
Chicago, Illinois, 60612
Newark, New Jersey, 07112
Springfield, Illinois, 62702
Quebec, G1V 4G2
Lebanon, New Hampshire, 03756
Miami, Florida, 33155
Corpus Christi, Texas, 78411
Atlanta, Georgia, 30322
Chicago, Illinois, 60637
Oakland, California, 94609
Orlando, Florida, 32827
Las Vegas, Nevada, 89135
Hollywood, Florida, 33021
San Antonio, Texas, 78229
London, Ontario, N6A 5W9
Rochester, New York, 14642
Fort Myers, Florida, 33908
Salt Lake City, Utah, 84113
New York, New York, 10032
Savannah, Georgia, 31404
San Diego, California, 92123
Stony Brook, New York, 11794
Madera, California, 93636
New Haven, Connecticut, 06520

Tracking Information

NCT #
NCT01780662
Collaborators
Not Provided
Investigators
  • Principal Investigator: Peter D Cole Children's Oncology Group
  • Peter D Cole Children's Oncology Group