Clinical trial NCT01842672: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
Lymphoblastic Lymphoma
Diffuse Large B-cell Lymphoma
Burkitt Lymphoma/Leukemia
Keywords: pediatric non-hodgkins lymphoma
pediatric acute leukemia
clofarabine
mitoxantrone
Lead sponsor: New York Medical College
Sponsor class: OTHER
First posted: 2013-04-30
Enrollment: 41
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Determine MTD
timeFrame: 100 days
Secondary outcomes:
measure: Response Rate
timeFrame: 1 year
measure: Monitor for Minimal Residual Disease
timeFrame: 1 Year
Other outcomes:
Locations:
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
Study officials:
References: