Clinical Trials /

Mitoxantrone and Clofarabine for Treatment of Recurrent NHL or Acute Leukemia

NCT01842672

Description:

The combination of mitoxantrone and clofarabine as reinduction therapy will be safe, well tolerated and effective in children, adolescents and young adults with poor risk refractory/relapsed acute leukemia and high grade non-Hodgkin lymphoma (NHL).

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Burkitt Leukemia
  • Burkitt Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Lymphoblastic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Mitoxantrone and Clofarabine for Treatment of Recurrent NHL or Acute Leukemia
  • Official Title: A Pilot Study of Mitoxantrone in Combination With Clofarabine (MITCL) in Children, Adolescents and Young Adults (CAYA) With Refractory/Relapsed Acute Leukemia or High Grade Non-Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: NYMC 542
  • SECONDARY ID: L 10, 819
  • NCT ID: NCT01842672

Conditions

  • Acute Lymphoblastic Leukemia
  • Acute Myelogenous Leukemia
  • Lymphoblastic Lymphoma
  • Diffuse Large B-cell Lymphoma
  • Burkitt Lymphoma/Leukemia

Interventions

DrugSynonymsArms
ClofarabineClolar™, Evoltra, NSC# 606,869, IND # 73,789Mitoxantrone/Clofarabine
MitoxantroneNovantroneMitoxantrone/Clofarabine

Purpose

The combination of mitoxantrone and clofarabine as reinduction therapy will be safe, well tolerated and effective in children, adolescents and young adults with poor risk refractory/relapsed acute leukemia and high grade non-Hodgkin lymphoma (NHL).

Trial Arms

NameTypeDescriptionInterventions
Mitoxantrone/ClofarabineExperimentalClofarabine Dose escalation starting 20 mg/m2/d days 1-5 Mitoxantrone 12 mg/m2/d days 3-6. Rituximab in patient with CD20+ disease only 375 mg/m2 day 1, 8, 15. IT Depocyt 35 or 50 mg/dose day 1 per cycle. IT ARA-C in children < 3 years age based dosing.
  • Clofarabine
  • Mitoxantrone

Eligibility Criteria

        Inclusion Criteria:

        Age ≤30.99 years old

        Disease Status (Part A - Safety Phase)

          -  ALL in 1st, 2nd or 3rd relapse OR primary induction failure.

          -  AML in 1st ,2nd or 3rd relapse OR primary induction failure.

          -  T-or B -- Lymphoblastic Lymphoma (T-LBL, B-LBL); Diffuse Large B-cell Lymphoma (DLBCL)
             or Burkitt Lymphoma/Leukemia in 1st, 2nd or 3rd relapse OR primary induction failure.

        5.1.2.2 (Part B - Efficacy Phase)

          -  ALL in 2nd or 3rd relapse OR primary induction failure.

          -  AML in 2nd or 3rd relapse OR primary induction failure.

          -  T-or B -- Lymphoblastic Lymphoma (T-LBL, B-LBL); Diffuse Large B-cell Lymphoma (DLBCL)
             or Burkitt Lymphoma/Leukemia in 1st, 2nd or 3rd relapse OR primary induction failure.

        Adequate renal function defined as:

        - Normal Serum creatinine based on age or Creatinine clearance > 60 ml/min or >60
        ml/min/1.73 m2 or an equivalent radioisotope glomerular filtration rate (GFR) as determined
        by the institutional normal range.

        Adequate liver function defined as:

          -  Direct bilirubin < 1.5 upper limit of normal (ULN) for age, and SGOT (AST) or SGPT
             (ALT) <3 x ULN

        Adequate cardiac function defined as:

          -  Shortening fraction >27% by echocardiogram, or

          -  Ejection fraction of >50% by radionuclide angiogram or echocardiogram.

        Performance Status

          -  For patients age 1-16 years, Lansky score of ≥60.

          -  For patients > 16 years, Karnofsky score of ≥60.

        Negative urine pregnancy test for females of child bearing age.

        Prior Therapy - Patients are eligible if they have been treated with clofarabine,
        mitoxantrone, or a combination of both in the past. However, the maximal lifetime
        cumulative previous anthracycline dose should not exceed doxorubicin dose equivalent of 450
        mg/m2 (see Table 1). Patients who received more than one anthracycline prior to study entry
        should have each individual agent cumulative dose converted to doxorubicin equivalent and
        added together (eg, a patient who received cumulative dose of Daunorubicin at 200 mg/m2 and
        Mitoxantrone 48 mg/m2 has a total doxorubicin dose equivalent of 358.6 mg/m2 (200 mg/m2 x
        0.833 + 48 mg/m2 x 4).

        Table 1. Anthracycline Conversion Agent Conversion Factor to Doxorubicin Dose Doxorubicin
        Multiply total dose x 1 Daunorubicin Multiply total dose x 0.833 Idarubicin Multiply total
        dose x 5 Mitoxantrone Multiply total dose x 4

        Informed Consent

        - Patients or the patient's legally authorized guardian must be fully informed about their
        illness and the investigational nature of this protocol (including foreseeable risks and
        possible side effects), and must sign an informed consent in accordance with the
        institutional policies approved by the U.S. Department of Health and Human Services.

        Exclusion Criteria:

        Patients with prior myeloablative allogeneic stem cell transplantation <3 months prior to
        proposed enrollment on study and/or ≥Grade II active acute GVHD or extensive chronic GVHD.

        Females who are pregnant (positive HCG) or lactating.

        Karnofsky <60% or Lansky <60% if less than 16 years of age.

        Age >30.99 years of age.

        Patients with active CNS disease.

        Any patient with uncontrolled infection prior to study entry.

        Patients with Down syndrome are excluded.
      
Maximum Eligible Age:30 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine MTD
Time Frame:100 days
Safety Issue:
Description:2.1 To determine the maximal tolerated dose (MTD) and/or tolerable dose of escalating doses of clofarabine starting from 20mg/m2/day to 40mg/m2/day from Day 1 to Day 5 in combination with mitoxantrone 12mg/m2/day on Day 3-6 as reinduction therapy for children, adolescents and young adults with poor risk refractory/relapsed acute leukemia or high grade NHL.

Secondary Outcome Measures

Measure:Response Rate
Time Frame:1 year
Safety Issue:
Description:To determine the overall complete and partial response rate (OR) of the combination of mitoxantrone and clofarabine as reinduction therapy for children, adolescents and young adults with refractory/relapsed acute leukemia or high grade NHL.
Measure:Monitor for Minimal Residual Disease
Time Frame:1 Year
Safety Issue:
Description:To determine the percent of minimal residual disease (MRD) in the peripheral blood following reinduction with mitoxantrone and clofarabine reinduction therapy.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:New York Medical College

Trial Keywords

  • pediatric non-hodgkins lymphoma
  • pediatric acute leukemia
  • clofarabine
  • mitoxantrone

Last Updated

March 11, 2019