Clinical Trials /

Chemotherapy With Liposomal Cytarabine CNS Prophylaxis for Adult Acute Lymphoblastic Leukemia & Lymphoblastic Lymphoma

NCT02043587

Description:

The objective of this protocol is to improve survival for adults with acute lymphoblastic leukemia or acute lymphoblastic lymphoma by reducing systemic and central nervous system (CNS) relapse with acceptable toxicity using intensive chemotherapy with liposomal cytarabine (Depocyt®) CNS prophylaxis.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Chemotherapy</span> With <span class="go-doc-concept go-doc-intervention">Liposomal Cytarabine</span> <span class="go-doc-concept go-doc-disease">CNS</span> Prophylaxis for Adult <span class="go-doc-concept go-doc-disease">Acute Lymphoblastic Leukemia</span> & Lymphoblastic Lymphoma

Title

  • Brief Title: Chemotherapy With Liposomal Cytarabine CNS Prophylaxis for Adult Acute Lymphoblastic Leukemia & Lymphoblastic Lymphoma
  • Official Title: A Phase II Study of Punctual, Cyclic, and Intensive Chemotherapy With Liposomal Cytarabine (Depocyt) CNS Prophylaxis for Adults With Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
  • Clinical Trial IDs

    NCT ID: NCT02043587

    ORG ID: 130934

    Trial Conditions

    Acute Lymphocytic Leukemia

    Adult Lymphoblastic Lymphoma

    Trial Interventions

    Drug Synonyms Arms
    DNR Daunorubicin, Daunorubicin Hydrochloride, Cerubidine, Daunomycin, Rubidomycin Chemotherapy for ALL
    VCR Vincristine, Oncovin, Vincasar, PFS, Vincrex, Leurocritine, LCR Chemotherapy for ALL
    PEG-asp PEG-L-asparaginase, Oncaspar, PEG-asparaginase, pegasparagase Chemotherapy for ALL
    CTX Cyclophosphamide, Cytoxan, Endoxan, Neosar, Procytox, Revimmune, cytophosphane, CPM, CYT Chemotherapy for ALL
    Prednisone Deltasone Chemotherapy for ALL
    Liposomal AraC Liposomal cytarabine, DepoCyt Chemotherapy for ALL
    MTX Methotrexate, Rheumatrex, Trexall Chemotherapy for ALL
    LCV Leucovorin Chemotherapy for ALL
    AraC Cytarabine, Ara-C, Arabinosylcytosine, Cytosar-U Chemotherapy for ALL
    Etoposide VP-16, VePesid, Toposar Chemotherapy for ALL
    Dasatinib Sprycel Chemotherapy for ALL
    Rituximab Rituxan Chemotherapy for ALL
    Hydrocortisone Hydrocortisone sodium succinate, Solu-Cortef Chemotherapy for ALL

    Trial Purpose

    The objective of this protocol is to improve survival for adults with acute lymphoblastic
    leukemia or acute lymphoblastic lymphoma by reducing systemic and central nervous system
    (CNS) relapse with acceptable toxicity using intensive chemotherapy with liposomal
    cytarabine (Depocyt) CNS prophylaxis.

    Detailed Description

    This treatment regimen builds on the "Linker" regimen/UCSF Protocol 8707 ALL regimen
    backbone with the goal of improved efficacy and acceptable toxicity by substituting
    pegylated asparaginase for native L-asparaginase, the addition of rituximab for pre-B-cell
    ALL, and the addition of dasatinib for Philadelphia chromosome/BCR-ABL positive ALL, and the
    addition of cyclophosphamide for younger adults. In addition, the study regimen aims to
    reduce CNS relapse through the use of intrathecal liposomal cytarabine in place of
    intrathecal methotrexate for CNS relapse prophylaxis and

    The regimen uses 3 modules of therapy with non-cross-resistant chemotherapy agents.
    Rituximab is added for a total of 8 doses for patients with pre-B-cell ALL. Dasatinib is
    added for patients with Ph+ ALL.

    Course 1A (Induction): Daunorubicin, vincristine, PEG-asparaginase, and prednisone for all
    patients with the addition of cyclophosphamide for patients 18-39 years of age. Treatment is
    intensified for patients with disease present on a day 14 bone marrow biopsies during
    Induction Course 1A. In addition to standard analyses, minimal residual disease will be
    assessed on day 14 and remission bone marrow aspirates and correlated with outcomes.

    Course 1B: High-dose methotrexate, oral 6-mercaptopurine, and PEG-asparaginase.

    Course 1C: High-dose cytarabine and etoposide.

    The 3 courses then repeat (2A (Intensification), 2B, 2C) followed by a final "B" cycle (3B)
    of high-dose methotrexate, 6-mercaptopurine, and PEG-asparaginase.

    After completion of Course 3B, patients proceed to maintenance chemotherapy with monthly
    methotrexate, vincristine, 6-mercaptopurine, and prednisone cycles for 24 months with a
    single dose PEG-asparaginase given in month 1 of Maintenance.

    CNS prophylaxis: Intrathecal liposomal cytarabine replaces intrathecal methotrexate CNS
    prophylaxis and is given every 2 weeks during the "A" Induction and Intensification courses
    then every 3 months during Maintenance for a total of 8 doses. Given the presence of CNS
    penetrating chemotherapy in the "B" and "C" cycles, intrathecal liposomal cytarabine is not
    given due to risk of excessive CNS toxicity.

    There is a randomization to hydrocortisone or placebo premedication prior to
    PEG-asparaginase.

    Trial Arms

    Name Type Description Interventions
    Chemotherapy for ALL Experimental Course 1A: DNR 60 mg/m2 IV d1,2,3; VCR 1.4 mg/m2 d1,8,15,22 (cap 2 mg age >50); PEG-asp 2000 IU/m2 IV d16, age >50 1000 IU/m2, cap 3750 IU/m2; CTX 750 mg/m2 d1,15 age < 40; Prednisone 60 mg/m2 PO d1-28; Liposomal AraC 25 mg IT d1, 15 1B: MTX 220 mg/m2 IV then 60 mg/m2/h for 36h d2-3,d16-17; LCV 50 mg/m2 IV q6h x3 then 10 mg/m2 PO/IV q6h til MTX <0.1 uM; 6-MP 60 mg/m2 PO d2-8, d16-22; PEG-asp 2000 IU/m2 IV d18, age >50 1000 IU/m2, cap 3750 IU/m2 1C: AraC 2 g/m2 IV d1-4; Etoposide 500 mg/m2 IV d1-4 1A-C repeat x1(2A-C) then 3rd Course B (3B) Maintenance (monthly, 24 mo): Prednisone 60 mg/m2 PO d1-5; VCR 1.4 mg/m2 IV d1 (cap 2 mg age >50); MTX 20 mg/m2 PO wkly; 6-MP 60 mg/m2 PO qd PEG-asp 2000 IU/m2 IV d16, age >50 1000 IU/m2, cap 3,750 IU/m2 (Mo. 1) Maintenance mo. 1-4: Liposomal AraC 50 mg IT d1 Dasatinib 140 mg PO qd if Ph/BCR-ABL+; Rituximab 375 mg/m2 IV d1,15 of 1A-C, 2A (Pre-B) 1:1 randomization: hydrocortisone v. placebo before PEG-asp 1B, 2B, & Maint. DNR, VCR, PEG-asp, CTX, Prednisone, Liposomal AraC, MTX, LCV, AraC, Etoposide, Dasatinib, Rituximab, Hydrocortisone

    Eligibility Criteria

    Inclusion Criteria:

    - Ability to understand and the willingness to sign a written informed consent.

    - Diagnosis of acute lymphoblastic leukemia or lymphoblastic lymphoma as defined by the
    World Health Organization [94]

    - Untreated disease EXCEPT for corticosteroids, hydroxyurea, leukapheresis, and/or
    tyrosine kinase inhibitors for up to 2 weeks prior to initiation of study therapy.

    - Age 18 through 60 years

    - ECOG performance status 0,1, or 2 (see Appendix A)

    - Adequate organ function defined as:

    - Total bilirubin < 2 mg/dL (unless due to ALL)

    - AST(SGOT)/ALT(SGPT) < 3 times institutional upper limit of normal (unless due to
    ALL)

    - Serum creatinine < 2 mg/dL (unless elevated creatinine felt by investigator to be
    acute and reversible) OR creatinine clearance >60 mL/min/1.73 m2 for patients with
    creatinine levels above institutional normal

    - Left ventricular ejection fraction 50%

    - Women of child-bearing potential and men with partners of child- bearing potential
    must agree to use adequate contraception (hormonal or barrier method of birth
    control; abstinence) prior to study entry, for the duration of study participation,
    and for 90 days following completion of therapy. Should a woman become pregnant or
    suspect she is pregnant while participating in this study, she should inform her
    treating physician immediately.

    - A woman of child-bearing potential is any female (regardless of sexual orientation,
    having undergone a tubal ligation, or remaining celibate by choice) who meets the
    following criteria:

    - Has not undergone a hysterectomy or bilateral oophorectomy; or

    - Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
    has had menses at any time in the preceding 12 consecutive months)

    Exclusion Criteria:

    - Current or anticipated use of other investigational agents during the study

    - Known central nervous system mass lesion

    - History of allergic reactions attributed to compounds of similar chemical or biologic
    composition to liposomal cytarabine or other agents used in study inclusive of known
    allergy to polyethylene glycol.

    - History of unprovoked venous thrombosis/thromboembolism

    - Recurrent or chronic pancreatitis

    - Uncontrolled diabetes mellitus

    - Uncontrolled intercurrent illness that would limit compliance with study requirements
    including, but not limited to, ongoing or active infection, symptomatic congestive
    heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
    illness/social situations that would limit compliance with study requirements.

    - Pregnant or nursing.

    - Any condition, in the opinion of the investigator, that compromises compliance with
    study requirements

    - Known HIV positivity

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 60 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Event-free survival

    Secondary Outcome Measures

    Liposomal cytarabine toxicity

    CNS relapse rate

    Overall survival

    Leukemia-free survival

    Efficacy of hydrocortisone premedication for reduced PEG-asparaginase allergic reactions

    PEG-asparaginase toxicities

    Complete and overall response rates

    Non-relapse mortality

    Trial Keywords

    Acute lymphoblastic leukemia

    Lymphoblastic leukemia

    Lymphoblastic lymphoma