Temsirolimus, Dexamethasone, Mitoxantrone Hydrochloride, Vincristine Sulfate, and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma
Condition: Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma
MeSH terms: Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, T-Cell; Recurrence
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase I trial studies the side effects and the best dose of temsirolimus when given
      together with dexamethasone, mitoxantrone hydrochloride, vincristine sulfate, and
      pegaspargase in treating young patients with relapsed acute lymphoblastic leukemia or
      non-Hodgkin lymphoma. Temsirolimus may stop the growth of cancer cells by blocking some of
      the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone,
      mitoxantrone hydrochloride, vincristine sulfate, and pegaspargase work in different ways to
      stop the growth of cancer cells, either by killing the cells or by stopping them from
      dividing. Giving temsirolimus with combination chemotherapy may be and effective treatment
      for acute lymphoblastic leukemia or non-Hodgkin lymphoma.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To estimate the maximum-tolerated dose (MTD) and/or recommended phase 2 dose of
      temsirolimus administered weekly for 2 doses in combination with intensive re-induction
      chemotherapy in children with relapsed acute lymphoblastic leukemia (ALL) or non-Hodgkin
      lymphoma (NHL).

      II. To define and describe the toxicities of temsirolimus in combination with intensive
      re-induction chemotherapy in children with relapsed ALL or NHL administered on this schedule.

      SECONDARY OBJECTIVES:

      I. To compare minimal-residual disease (MRD) levels present at end of induction to historical
      control in patients with relapsed ALL or NHL with bone marrow involvement of disease.

      II. To determine the complete remission (CR) rate in patients with ALL or NHL who receive
      this regimen.

      III. To evaluate responsiveness of patient ALL cells to mammalian target of rapamycin (mTOR)
      inhibition using in vitro and in vivo pharmacodynamic assessment of the response of ALL
      blasts to temsirolimus.

      OUTLINE: This is a dose-escalation study of temsirolimus.

      Patients receive dexamethasone orally (PO) or intravenously (IV) on days 1-5 and 15-19;
      mitoxantrone hydrochloride IV over 30 minutes on days 1-2; temsirolimus IV over 30 minutes on
      days 1 and 8; vincristine sulfate IV on days 1, 8, 15, and 22; and pegaspargase IV over 1
      hour on days 3 and 17. Some patients may also receive methotrexate intrathecally (IT) up to
      72 hours prior to or on day 1 and on day 8.

      After completion of study therapy, patients are followed up for 30 days.
    

Intervention name(s): Dexamethasone; Laboratory Biomarker Analysis; Methotrexate; Mitoxantrone Hydrochloride; Pegaspargase; Pharmacological Study; Temsirolimus; Vincristine Sulfate
Intervention type(s): Drug; Other; Drug; Drug; Drug; Other; Drug; Drug
Intervention description(s): Given PO or IV; Correlative studies; Given IT; Given IV; Given IV; Correlative studies; Given IV; Given IV
Other intervention name(s): Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; Visumetazone; Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate; Mexate-AQ; MTX; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039; CL 232315; DHAD; DHAQ; Dihydroxyanthracenedione Dihydrochloride; Mitoxantrone Dihydrochloride; Mitoxantroni Hydrochloridum; Mitozantrone Hydrochloride; Mitroxone; Neotalem; Novantrone; Onkotrone; Pralifan; L-Asparaginase with Polyethylene Glycol; Oncaspar; PEG-Asparaginase; PEG-L-Asparaginase; PEG-L-Asparaginase (Enzon - Kyowa Hakko); PEGLA; Polyethylene Glycol L-Asparaginase; Polyethylene Glycol-L-Asparaginase; CCI-779; CCI-779 Rapamycin Analog; Cell Cycle Inhibitor 779; Rapamycin Analog; Rapamycin Analog CCI-779; Torisel; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Oncovin; Vincasar; Vincosid; Vincrex; Vincristine, sulfate
Intervention MeSH terms: Sirolimus; Dexamethasone; Dexamethasone acetate; Methotrexate; Vincristine; Asparaginase; Temsirolimus; Mitoxantrone; Pegaspargase; MTOR Inhibitors; BB 1101
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment