MITCL: Mitoxantrone and Clofarabine for Treatment of Recurrent NHL or Acute Leukemia

Sponsor
New York Medical College (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01842672
Collaborator
(none)
41
Enrollment
2
Locations
1
Arm
105
Duration (Months)
20.5
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Study Design

Study Type:
Interventional
Actual Enrollment :
41 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Study Start Date :
Mar 1, 2013
Actual Primary Completion Date :
Aug 1, 2021
Anticipated Study Completion Date :
Dec 1, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: Mitoxantrone/Clofarabine

Clofarabine 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.

Drug: Clofarabine
Dose Escalation of Clofarabine
Other Names:
  • Clolar™
  • Evoltra
  • NSC# 606,869
  • IND # 73,789
  • Drug: Mitoxantrone
    Other Names:
  • Novantrone
  • Outcome Measures

    Primary Outcome Measures

    1. Determine MTD [100 days]

      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

    1. Response Rate [1 year]

      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.

    2. Monitor for Minimal Residual Disease [1 Year]

      To determine the percent of minimal residual disease (MRD) in the peripheral blood following reinduction with mitoxantrone and clofarabine reinduction therapy.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 30 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1New York Medical CollegeValhallaNew YorkUnited States10595
    2Levine Children's HospitalCharlotteNorth CarolinaUnited States28204

    Sponsors and Collaborators

    • New York Medical College

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    New York Medical College
    ClinicalTrials.gov Identifier:
    NCT01842672
    Other Study ID Numbers:
    • NYMC 542
    • L 10, 819
    First Posted:
    Apr 30, 2013
    Last Update Posted:
    Nov 3, 2021
    Last Verified:
    Oct 1, 2021

    Study Results

    No Results Posted as of Nov 3, 2021