Trial Search Results

Lenalidomide and Dinutuximab With or Without Isotretinoin in Treating Younger Patients With Refractory or Recurrent Neuroblastoma

This phase I trial studies the side effects and best dose of lenalidomide when given together with dinutuximab with or without isotretinoin in treating younger patients with neuroblastoma that does not respond to treatment or that has come back. Drugs used in chemotherapy, such as lenalidomide and isotretinoin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as dinutuximab, may interfere with the ability of tumor cells to grow and spread. Giving more than one drug (combination chemotherapy) together with dinutuximab therapy may kill more tumor cells.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: Dinutuximab
  • Drug: Isotretinoin
  • Other: Laboratory Biomarker Analysis
  • Drug: Lenalidomide
  • Other: Pharmacological Study

Phase:

Phase 1

Eligibility


Inclusion Criteria:

   - Patients must have a diagnosis of neuroblastoma either by histologic verification of
   neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased
   urinary catecholamines

   - Patients must have high-risk neuroblastoma

   - Patients must have at least ONE of the following:

      - Recurrent/progressive disease at any time prior to enrollment - regardless of
      response to frontline therapy

      - Refractory disease: persistent sites of disease (after less than a partial
      response to frontline therapy, following a minimum of 4 cycles of induction
      therapy) AND patient has never had a relapse/progression

      - Persistent disease: persistent disease after achieving at least a partial
      response to frontline therapy after a minimum of 4 cycles of induction therapy
      and patient has never had a relapse/progression

   - Patients must have at least ONE of the following (lesions may have received prior
   radiation therapy as long as they meet the other criteria listed below):

      - Bone disease

         - At least one metaiodobenzylguanidine (MIBG) avid bone site or diffuse MIBG
         uptake

            - For recurrent/progressive or refractory disease a biopsy is not
            required regardless of number of MIBG avid lesions

            - For persistent disease, if patient has only 1 or 2 MIBG avid lesions OR
            a Curie score of 1-2, then biopsy confirmation of neuroblastoma and/or
            ganglioneuroblastoma in at least one site present at the time of
            enrollment (bone marrow, bone, or soft tissue) is required to be
            obtained at any time point prior to enrollment and two weeks subsequent
            to most recent prior therapy; if a patient has 3 or more MIBG avid
            lesions OR a Curie score of >= 3 then no biopsy is required for
            eligibility

         - If a tumor is known to be MIBG non-avid, then a patient must have at least
         one fludeoxyglucose (FDG)-positron emission tomography (PET) avid bone site
         present at the time of enrollment with biopsy confirmation of neuroblastoma
         and/or ganglioneuroblastoma obtained at any time prior to enrollment and two
         weeks subsequent to most recent prior therapy

      - Any amount of neuroblastoma tumor cells in the bone marrow based on routine
      morphology (with or without immunocytochemistry) in at least one sample from
      bilateral aspirates and biopsies

      - At least one soft tissue lesion that meets the criteria for a TARGET lesion as
      defined by:

         - SIZE: Lesion can be accurately measured in at least one dimension with a
         longest diameter >= 10 mm, or for lymph nodes >= 15 mm on short axis;
         lesions meeting size criteria will be considered measurable

         - In addition to size, a lesion needs to meet ONE of the following criteria:

            - MIBG avid; for patients with persistent disease only: if a patient has
            only 1 or 2 MIBG avid lesions OR a Curie score of 1-2, then biopsy
            confirmation of neuroblastoma and/or ganglioneuroblastoma in at least
            one site present at time of enrollment (either bone marrow, bone and/or
            soft tissue) is required to be obtained at any time point prior to
            enrollment and at least two weeks subsequent to most recent prior
            therapy; if a patient has 3 or more MIBG avid lesions OR a Curie score
            of >= 3 then no biopsy is required for eligibility

            - FDG-PET avid (only if tumor is known to be MIBG non-avid); these
            patients must have had a biopsy confirming neuroblastoma and/or
            ganglioneuroblastoma in at least one FDG-PET avid site present at the
            time of enrollment done prior to enrollment and at least two weeks
            subsequent to the most recent prior therapy

            - Non-avid lesion (both MIBG and FDG-PET non-avid); these patients must
            have had a biopsy confirming neuroblastoma and/or ganglioneuroblastoma
            in at least one non-avid lesion present at the time of enrollment done
            prior to enrollment and at least two weeks subsequent to the most
            recent prior therapy

   - Patients with prior progressive disease who do not meet criteria above, are eligible
   as long as they have not been off treatment for > 3 months prior to enrollment on NANT
   2011-04

   - Patients must have a life expectancy of at least 6 weeks

   - Lansky (=< 16 years) or Karnofsky (> 16 years) score of at least 50

   - Patients must have fully recovered from the acute toxic effects of all prior
   chemotherapy, immunotherapy, or radiotherapy prior to study enrollment

   - Patients must not have received the therapies indicated below for the specified time
   period prior to the first day of administration of protocol therapy on this study

      - Myelosuppressive chemotherapy: must have received last dose at least 2 weeks
      prior to protocol therapy; this includes cytotoxic agents given on a low dose
      metronomic regimen

      - Biologic (anti-neoplastic agent) (includes retinoids): must have received last
      dose at least 7 days prior to protocol therapy

      - Monoclonal antibodies: must have received last dose at least 7 days or 3
      half-lives, whichever is longer, prior to protocol therapy

   - Radiation:

      - Patients must not have received radiation (small port) for a minimum of two weeks
      prior to protocol therapy

      - Except for patients with a history of progressive disease, patients whose only
      site(s) of disease have been radiated are eligible if at least one lesion meets
      at least one of the criteria listed in sites of disease above

      - A minimum of 12 weeks prior to start of protocol therapy is required following
      large field radiation therapy (i.e. total body irradiation, craniospinal, whole
      abdominal, total lung, > 50% marrow space)

      - A minimum of 6 weeks must have elapsed prior to start of protocol therapy for
      other substantial bone marrow radiation

   - Stem Cell Transplant (SCT):

      - Patients are eligible 6 weeks after date of autologous stem cell infusion
      following myeloablative therapy (timed from first day of protocol therapy)

      - Patients are not eligible post allogeneic stem cell transplant

      - Patients who have received an autologous stem cell infusion to support
      non-myeloablative therapy (such as 131 iodine [I]-MIBG) are eligible at any time
      as long as they meet the other criteria for eligibility

   - A minimum of 6 weeks must have elapsed after 131I-MIBG therapy prior to start of
   protocol therapy

   - Prior anti-disialoganglioside (GD2) antibody, isotretinoin, or lenalidomide therapy:

      - Patients who have received prior anti-GD2 antibody therapy are eligible if they
      did not have tumor relapse/progression while receiving this therapy

      - Patients who have received either isotretinoin or lenalidomide are eligible, but
      not if they have received the two agents concomitantly

   - All cytokines or hematopoietic growth factors must be discontinued a minimum of 7 days
   prior to protocol therapy

   - Patients must not be receiving any other anti-cancer agents or radiotherapy at the
   time of study entry or while on study

   - Absolute phagocyte count (APC = neutrophils and monocytes): >= 1000/mm^3

   - Absolute neutrophil count: >= 750/mm^3

   - Platelet count: >= 50,000/mm^3, transfusion independent (no platelet transfusions
   within 1 week)

   - Hemoglobin >= 8.0 (may transfuse)

   - Patients with known bone marrow metastatic disease will be eligible for study as long
   as they meet hematologic function criteria; patients with marrow disease are not
   evaluable for hematologic toxicity

   - Age-adjusted serum creatinine =< 1.5 x normal for age or creatinine clearance or
   glomerular filtration rate (GFR) >= 60 cc/min/1.73 m^2

      - Age 1 month to < 6 months: 0.4 mg/dL for males and 0.4 mg/dL for females

      - Age 6 months to < 1 year: 0.5 mg/dL for males and 0.5 mg/dL for females

      - Age 1 to < 2 years: 0.6 mg/dL for males and 0.6 mg/dL for females

      - Age 2 to < 6 years: 0.8 mg/dL for males and 0.8 mg/dL for females

      - Age 6 to < 10 years: 1.0 mg/dL for males and 1.0 mg/dL for females

      - Age 10 to < 13 years: 1.2 mg/dL for males and 1.2 mg/dL for females

      - Age 13 to < 16 years: 1.5 mg/dL for males and 1.4 mg/dL for females

      - Age >= 16 years: 1.7 mg/dL for males and 1.4 mg/dL for females

   - =< grade 2 hematuria (criteria applicable only for dose levels that include
   isotretinoin) and =< grade 2 proteinuria

   - Total bilirubin =< 1.5 x upper limit of normal for age

   - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
   and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])
   =< 3 x upper limit of normal (note that for ALT, the upper limit of normal is defined
   as 45 U/L)

   - Sinusoidal obstruction syndrome (SOS) if present, must be stable or improving
   clinically

   - Cardiac function:

      - Normal ejection fraction (>= 55%) documented by either echocardiogram or
      radionuclide multi gated acquisition scan (MUGA) evaluation; OR

      - Normal fractional shortening (>= 27%) documented by echocardiogram

   - No dyspnea at rest

   - Serum triglyceride =< 300 mg/dL (applicable only for dose levels that include
   isotretinoin) (note that a non-fasting triglyceride value could be obtained, if this
   is > 300 mg/dL then a fasting triglyceride should be obtained and patient will be
   eligible if the fasting level is =< 300 mg/dL)

   - =< grade 2 hypercalcemia (applicable only for dose levels that include cis retinoic
   acid [RA])

   - Skin toxicity =< grade 1

   - All post-menarchal females must have a negative beta-human chorionic gonadotropin
   (HCG); males and females of reproductive age and childbearing potential must use
   effective contraception for the duration of their participation; females of
   childbearing potential (FCBP) must have a negative serum or urine pregnancy test with
   a sensitivity of at least 25 mIU/mL within 10-14 days and again within 24 hours prior
   to prescribing lenalidomide for cycle 1 and must either commit to continued abstinence
   from heterosexual intercourse or begin TWO acceptable methods of birth control, one
   highly effective method and one additional effective method AT THE SAME TIME, at least
   28 days before she starts taking lenalidomide; FCBP must also agree to ongoing
   pregnancy testing; men must agree to use a latex condom during sexual contact with a
   FCBP even if they have had a successful vasectomy

   - Patients with other ongoing serious medical issues must be approved by the study chair
   prior to registration

Exclusion Criteria:

   - Quantitative serum b-HCG must be negative 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; pregnant or breast-feeding women will not be
   entered on this study

   - Breast feeding women are not eligible

   - Patients who have an active or uncontrolled infection are excluded

   - Patients with a paraben allergy cannot take isotretinoin preparations containing this
   compound (i.e. Accutane, Sotret) but are eligible if they can take an alternate
   preparation without paraben; (applicable only for entry onto dose levels receiving
   isotretinoin)

   - Patients with a history of venous or arterial thrombosis personally before the age of
   40 years unless associated with a central line

   - Patients with a history of prior central nervous system (CNS) metastases or skull
   lesions with intracranial extension will be required to have a head computed
   tomography (CT) or magnetic resonance imaging (MRI) at study entry demonstrating no
   active CNS metastases; patients with skull metastases with associated intracranial
   soft tissue masses will remain eligible

   - Inability to swallow lenalidomide capsules whole; capsules of 13-isotretinoin may be
   opened

   - Patient declines participation in NANT 2004-05; unless the institution has been
   granted special exemption from mandatory enrollment on NANT 2004-05 by the NANT
   Operations Center

Ages Eligible for Study

N/A - 21 Years

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Peds Hem/Onc CRAs
Recruiting