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).
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
Drug | Synonyms | Arms |
---|
Clofarabine | Clolar™, Evoltra, NSC# 606,869, IND # 73,789 | Mitoxantrone/Clofarabine |
Mitoxantrone | Novantrone | Mitoxantrone/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
Name | Type | Description | Interventions |
---|
Mitoxantrone/Clofarabine | Experimental | 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. | |
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: | Unknown status |
Lead Sponsor: | New York Medical College |
Trial Keywords
- pediatric non-hodgkins lymphoma
- pediatric acute leukemia
- clofarabine
- mitoxantrone
Last Updated
March 13, 2019