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

October 24, 2022 updated by: New York Medical College

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

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

41

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Levine Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 30 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / 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: Mitoxantrone
Other Names:
  • Novantrone
Drug: Clofarabine
Dose Escalation of Clofarabine
Other Names:
  • Evoltra
  • Clolar™
  • NSC# 606,869
  • IND # 73,789

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine MTD
Time Frame: 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.
100 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rate
Time Frame: 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.
1 year
Monitor for Minimal Residual Disease
Time Frame: 1 Year
To determine the percent of minimal residual disease (MRD) in the peripheral blood following reinduction with mitoxantrone and clofarabine reinduction therapy.
1 Year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York Medical College

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (ACTUAL)

August 1, 2021

Study Completion (ACTUAL)

September 1, 2022

Study Registration Dates

First Submitted

April 22, 2013

First Submitted That Met QC Criteria

April 29, 2013

First Posted (ESTIMATE)

April 30, 2013

Study Record Updates

Last Update Posted (ACTUAL)

October 25, 2022

Last Update Submitted That Met QC Criteria

October 24, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NYMC 542
  • L 10, 819 (OTHER: New York Medical College Institutional Review Board)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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