Crizotinib and Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma
Condition: Childhood Solid Neoplasm; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Neuroblastoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Neuroblastoma; Lymphoma, Large-Cell, Anaplastic; Recurrence
Intervention: Crizotinib; Cyclophosphamide; Dexrazoxane Hydrochloride; Doxorubicin Hydrochloride; Laboratory Biomarker Analysis; Pharmacological Study; Questionnaire Administration; Topotecan Hydrochloride; Vincristine Sulfate
Intervention description: Given PO; Given IV; Given IV; Given IV; Correlative studies; Correlative studies; Ancillary studies; Given IV; Given IV
Intervention MeSH terms: Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Vincristine; Topotecan; Crizotinib; Dexrazoxane; Razoxane; Tyrosine Protein Kinase Inhibitors
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 13 Months
Maximum age: 21 Years
Healthy volunteers: No
Keywords: Crizotinib; Chemotherapy; Solid Tumors; Anaplastic Large Cell Lymphoma

Summary:

      This phase I trial studies the side effects and the best dose of crizotinib when given
      together with combination chemotherapy in treating younger patients with solid tumors or
      anaplastic large cell lymphoma that has returned or does not respond to treatment. Crizotinib
      may stop the growth of tumor or cancer cells by blocking some of the enzymes needed for cell
      growth. Drugs used in chemotherapy, such as cyclophosphamide, topotecan hydrochloride,
      dexrazoxane hydrochloride, doxorubicin hydrochloride, and vincristine sulfate, work in
      different ways to stop the growth of cancer cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. Giving crizotinib together with
      combination chemotherapy may be a better treatment for patients with solid tumors or
      anaplastic large cell lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have had histologic verification of malignancy at original diagnosis or
             relapse; all patients with relapsed or refractory solid tumors or anaplastic large
             cell lymphoma (ALCL) are eligible except for patients with primary or metastatic
             central nervous system (CNS) tumors or patients with primary cutaneous ALCL

          -  Patients must have either measurable or evaluable disease

          -  Patients current disease state must be one for which there is no known curative
             therapy or therapy proven to prolong survival with an acceptable quality of life

          -  Karnofsky >= 60% for patients > 16 years of age and Lansky >= 50 for patients =< 16
             years of age; Note: 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

               -  Myelosuppressive chemotherapy:

                    -  Solid tumors: at least 21 days after the last dose of myelosuppressive
                       chemotherapy (42 days if prior nitrosourea)

                    -  ALCL:

                         -  Patients with ALCL who relapse while receiving standard maintenance
                            chemotherapy will not be required to have a waiting period before
                            enrollment onto this study

                         -  Patients who relapse while they are not receiving standard maintenance
                            therapy, must have fully recovered from all acute toxic effects of
                            prior therapy; at least 14 days must have elapsed after the completion
                            of cytotoxic therapy

               -  Hematopoietic growth factors: 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

               -  Biologic (anti-neoplastic agent): 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

               -  Immunotherapy: at least 42 days after the completion of any type of
                  immunotherapy, e.g. tumor vaccines

               -  Monoclonal antibodies: at least 3 half-lives of the antibody after the last dose
                  of a monoclonal antibody

               -  Radiation therapy (XRT):

                    -  Solid tumors: at least 14 days after local palliative XRT (small port); >= 6
                       weeks must have elapsed since treatment with therapeutic doses of
                       metaiodobenzylguanidine (MIBG); 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

                    -  ALCL: at least 14 days after local palliative XRT (small port); at least 84
                       days must have elapsed if prior TBI, craniospinal XRT or if >= 50% radiation
                       of pelvis; at least 42 days must have elapsed if other substantial BM
                       radiation

               -  Stem cell infusion without TBI: no evidence of active graft vs. host disease and
                  at least 84 days must have elapsed after transplant and >= 42 days for autologous
                  stem cell infusion after iodine (I)131-MIBG therapy

               -  Patients must not have received prior therapy with crizotinib

               -  Prior anthracycline dose: patients with a total lifetime cumulative anthracycline
                  dose of > 650 mg/m^2 at the time of enrollment are not eligible for Part B of the
                  study

          -  For patients with solid tumors or ALCL without known bone marrow involvement:

               -  Peripheral absolute neutrophil count (ANC) >= 1000/mm^3

               -  Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
                  platelet transfusions for at least 7 days prior to enrollment)

          -  Patients with known bone marrow metastatic disease will be eligible for study provided
             they meet the blood counts (may receive transfusions provided they are not known to be
             refractory to red cell or platelet transfusions); these patients will not be evaluable
             for hematologic toxicity; if dose-limiting hematologic toxicity is observed, all
             subsequent patients enrolled 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:

               -  Age 1 to < 2 years: 0.6 mg/dL

               -  Age 2 to < 6 years: 0.8 mg/dL

               -  Age 6 to < 10 years: 1 mg/dL

               -  Age 10 to < 13 years: 1.2 mg/dL

               -  Age 13 to < 16 years: 1.5 mg/dL (males) and 1.4 mg/dL (females)

               -  Age >= 16 years: 1.7 mg/dL (males) and 1.4 mg/dL (females)

          -  Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
             age

          -  Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110
             U/L; for the purpose of this study, the ULN for SGPT is 45 U/L

          -  Serum albumin >= 2 g/dL

          -  Corrected QT interval (QTc) =< 480 msec

          -  For patients on Part B: shortening fraction of >= 27% by echocardiogram or ejection
             fraction of >= 50% by gated radionuclide study

          -  All patients and/or their parents or legally authorized representatives must sign a
             written informed consent; assent, when appropriate, will be obtained according to
             institutional guidelines

          -  Part C: Patients must have a body surface area (BSA) >= 1.07 m^2 at the time of study
             enrollment

          -  Part D: Patients must have a body surface area (BSA) >= 0.43 m^2 at the time of study
             enrollment

          -  Tumor tissue must be sent; if tumor tissue is unavailable, the study chair must be
             notified prior to enrollment

        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 treatment and for 3 months after stopping treatment

          -  Patients receiving corticosteroids who have not been on a stable or decreasing dose of
             corticosteroid for at least 7 days prior to enrollment are not eligible

          -  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 are receiving cyclosporine, tacrolimus or other agents to prevent
             graft-versus-host disease post bone marrow transplant are not eligible for this trial

          -  Patients chronically receiving medications known to be metabolized by cytochrome P
             450, family 3, subfamily A, polypeptide 4 (CYP3A4) and with narrow therapeutic indices
             including pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not
             eligible; the topical use of these medications (if applicable) is allowed

          -  Patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7
             days prior to study enrollment, including but not limited to ketoconazole,
             itraconazole, miconazole, clarithromycin, erythromycin, ritonavir, indinavir,
             nelfinavir, saquinavir, amprenavir, delavirdine, nefazodone, diltiazem, verapamil, and
             grapefruit juice are not eligible; the topical use of these medications (if
             applicable), e.g. 2% ketoconazole cream, is allowed

          -  Patients chronically receiving drugs that are known potent CYP3A4 inducers within 12
             days prior to study enrollment, including but not limited to carbamazepine,
             phenobarbital, phenytoin, rifabutin, rifampin, tipranavir, ritonavir, and St. John?s
             wort are not eligible; the topical use of these medications (if applicable) is allowed

          -  Patients receiving PPIs and H2 blockers are not eligible for Part D

          -  Patients who have an uncontrolled infection are not eligible

          -  Patients who have received a prior solid organ transplantation are not eligible

          -  Patients who have a primary or metastatic CNS tumor at the time of study enrollment
             are not eligible; a prior history of metastatic CNS tumor is allowed as long as there
             is no evidence of CNS disease at study enrollment

          -  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

          -  Parts A and B: Patients who are able to swallow liquid or use a nasogastric or
             gastrostomy (G) tube are eligible

          -  Part C: Patients must be able to swallow intact capsules

          -  Part D: Patients must be able to swallow liquid