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

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 ( = 8 weeks (>= 56 days)
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients = = 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:
• = = 13 years of age)
• = = 16 years of age)
• Bilirubin (sum of conjugated + unconjugated) = = 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 w