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

Not Recruiting

Trial ID: NCT01780662


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.

Official Title

A Phase 1/2 Study of Brentuximab Vedotin (SGN35) in Combination With Gemcitabine for Pediatric and Young Adult Patients With Relapsed or Refractory Hodgkin Lymphoma

Stanford Investigator(s)


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

   - 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

      - At least 3 half-lives of the antibody after the last dose of a monoclonal

      - 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


   - 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)


   - 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

   - 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

   - 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

      - 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

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


drug: brentuximab vedotin

drug: gemcitabine hydrochloride

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Christina Baggott

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