Clinical Trials /

Intravenous Erwinia Chrysanthemi Asparaginase in Patients With Newly Diagnosed Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia Aged 60 Years or Older

NCT02647190

Description:

The purpose of this study is to test the safety of Erwinia Chrysanthemi asparaginase when used alone and together with chemotherapy and find out what effects, if any, it has on people.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Withdrawn

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02647190

Trial Eligibility

Document

Title

  • Brief Title: Intravenous Erwinia Chrysanthemi Asparaginase in Patients With Newly Diagnosed Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia Aged 60 Years or Older
  • Official Title: A Phase I Study to Determine the Safety and Pharmacokinetics of Intravenous Erwinia Chrysanthemi Asparaginase in Patients With Newly Diagnosed Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia Aged 60 Years or Older

Clinical Trial IDs

  • ORG STUDY ID: 15-107
  • NCT ID: NCT02647190

Conditions

  • Acute Lymphoblastic Leukemia (ALL)
  • Newly Diagnosed Philadelphia Chromosome Negative
  • Aged 60 Years or Older

Interventions

DrugSynonymsArms
Erwinia Chrysanthemi asparaginaseErwinia Chrysanthemi asparaginase

Purpose

The purpose of this study is to test the safety of Erwinia Chrysanthemi asparaginase when used alone and together with chemotherapy and find out what effects, if any, it has on people.

Detailed Description

      The study consists of three treatment phases.

        1. Steroid prophase (days -3 to -1):

           To prevent rapid leukemia progression and reduce tumor load, patients will receive
           either prednisone 60mg/m2 oral daily or equivalent corticosteroid daily for 3 days.

        2. Asparaginase phase (days 1 - 14):

           Patients will receive Erwinia asparaginase 25,000 IU/m2 IV three times a week on a
           Monday, Wednesday, Friday (MWF) schedule for 2 weeks. Patients are permitted to begin
           Erwinia asparaginase on Monday, Wednesday, or Friday, so that their schedules are
           defined as MWF, WFM, or FMW. For rapid progression of disease (defined by rising WBC
           >30K with > 50% peripheral blasts), prednisone 60mg/m2 oral daily or equivalent
           corticosteroid daily may be added.

           Bone marrow aspirate and/or biopsy will be performed on days 13-15 of the asparaginase
           treatment for early disease response assessment.

        3. Chemotherapy phase (days 15 - 42):

             -  Cyclophosphamide 650 mg/m2 IV on day 15

             -  Vincristine 1.4 mg/m2 (max 2mg) IV on days 15, 22, 29, and 36

             -  Prednisone 60mg/m2 (or equivalent corticosteroid) oral daily for 28 days on days 15
                - 42

             -  Erwinia asparaginase 25,000 IU/m2 IV three times a week on a MWF schedule for 2
                weeks on days 29 - 42 (after a two week interval without Erwinia asparaginase
                administered on days 1 - 14) Upon cell count recovery, a bone marrow aspirate
                and/or biopsy will be performed to assess the disease response. Subsequent
                treatments following the bone marrow evaluation will be left up to the discretion
                of the treating physicians. If the first 6 patients have no response or progress
                during the 2 weeks of asparaginase phase of treatment with or without steroid, the
                next 6 patients will start directly with the chemotherapy phase (days 15-42) of
                treatment consisting of cyclophosphamide, vincristine, and prednisone with Erwinia
                asparaginase.

      CNS prophylaxis:

        -  IT methotrexate 12mg (flat dose) between days 15 - 22

        -  IT methotrexate 12mg (flat dose) between days 22- 29

        -  There will be a minimal interval between doses of 7 days

Trial Arms

NameTypeDescriptionInterventions
Erwinia Chrysanthemi asparaginaseExperimentalThis is a phase I trial designed to assess the safety of IV Erwinia Chrysanthemi asparaginase during initial induction in patients aged 60 years or older with newly diagnosed Ph-negative ALL. A total of 12 patients will be accrued to the study.
  • Erwinia Chrysanthemi asparaginase

Eligibility Criteria

        Inclusion Criteria:

          -  Ages 60 years or older

          -  Previously untreated Philadelphia chromosome negative acute lymphoblastic leukemia

          -  No prior treatment for ALL, except steroids or hydroxyurea (stopped within 24 hour
             before start of protocol treatment)

          -  Serum creatinine ≤ 2 x upper limit of normal (ULN)

          -  Adequate liver function, including total bilirubin ≤ 1.5 x ULN unless the patient has
             documented Gilbert syndrome, and aspartate and alanine aminotransferase (AST and ALT)
             ≤ 5 x ULN. If organ function abnormalities are considered due to leukemic
             infiltration, total bilirubin must be ≤ 2 x ULN.

          -  ECOG performance status ≤3

          -  Male and female patients of childbearing potential must agree to use a highly
             effective method of contraception throughout the study and for a minimum of 90 days
             after the last dose of treatment on protocol. A patient is of childbearing potential
             if, in the opinion of the investigator, he/she is biologically capable of having
             children and is sexually active. Female patients who are not of childbearing potential
             should meet at least one of the following criteria:

               -  Have undergone hysterectomy or bilateral oophorectomy; or

               -  Have medically confirmed ovarian failure; or

               -  Are medically confirmed to be post-menopausal (cessation of regular menses for at
                  least 12 consecutive months with no alternative pathological or physiological
                  cause

        Exclusion Criteria:

          -  Lymphoblastic crisis of CML

          -  Mature B cell (Burkitt's) ALL

          -  Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic
             evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local
             treatment for active disease within the prior 28 days, symptomatic CNS leukemia (i.e.,
             cranial nerve palsies or other significant neurologic dysfunction) within 28 days.
             Prophylactic intrathecal medication is not a reason for exclusion.

          -  Pregnant women or women who are breast-feeding

          -  Concurrent active malignancy requiring immediate therapy

          -  Patients with human immunodeficiency virus (HIV)
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:proportion of patients who have a dose limiting toxicity (DLT)
Time Frame:with in 6 weeks of starting the study drug
Safety Issue:
Description:DLTs are defined as any of the following: grade 4 pancreatitis, grade 4 hemorrhage, grade 4 thromboembolism, grade 4 hyperbilirubinemia and any grade 5 toxicity attributable (definitely, probably or possible) to Erwinia asparaginase.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Withdrawn
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Erwinia Chrysanthemi Asparaginase
  • 15-107

Last Updated

June 2, 2017