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

Study Description

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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).

Condition or disease	Intervention/treatment	Phase
Acute Lymphoblastic Leukemia; Acute Myelogenous Leukemia; Lymphoblastic Lymphoma; Diffuse Large B-cell Lymphoma; Burkitt Lymphoma/Leukemia	Drug: Clofarabine; Drug: Mitoxantrone	Phase 1; Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	55 participants
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 :	March 2013
Estimated Primary Completion Date :	December 2018
Estimated Study Completion Date :	December 2018

Arms and Interventions

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

Outcome Measures

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Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.

Eligibility Criteria

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Ages Eligible for Study:	up to 30 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Contacts

Contact: Mitchell Cairo, MD	914-594-3650	mitchell_cairo@nymc.edu
Contact: Lauren Harrison, MSN	617-285-7844	lauren_harrison@nymc.edu

Locations

United States, New York
New York Medical College	Recruiting
Valhalla, New York, United States, 10595
Contact: Mitchell Cairo, MD 914-594-3650 mitchell_cairo@nymc.edu
Contact: Lauren Harrison, MSN 617-285-7844 lauren_harrison@nymc.edu
United States, North Carolina
Levine Children's Hospital	Recruiting
Charlotte, North Carolina, United States, 28204
Contact: Javier Oesterheld, MD 704-381-9900 Javier.Oesterheld@carolinashealthcare.org

Sponsors and Collaborators

New York Medical College

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	New York Medical College
ClinicalTrials.gov Identifier:	NCT01842672 History of Changes
Other Study ID Numbers:	NYMC 542; L 10, 819 ( Other Identifier: New York Medical College Institutional Review Board )
First Posted:	April 30, 2013
Last Update Posted:	March 29, 2018
Last Verified:	March 2018

Keywords provided by New York Medical College:

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

Additional relevant MeSH terms:

Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, B-Cell; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders	Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Mitoxantrone; Clofarabine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors