Mitoxantrone and Clofarabine for Treatment of Recurrent NHL or Acute Leukemia

NCT ID: NCT01842672

Last Updated: 2022-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2022-09-30

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).

Conditions

Acute Lymphoblastic Leukemia; Acute Myelogenous Leukemia; Lymphoblastic Lymphoma; Diffuse Large B-cell Lymphoma; Burkitt Lymphoma/Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Clofarabine

Intervention Type: DRUG

Dose Escalation of Clofarabine

Mitoxantrone

Intervention Type: DRUG

Interventions

Clofarabine

Dose Escalation of Clofarabine

Intervention Type: DRUG

Mitoxantrone

Intervention Type: DRUG

Other Intervention Names

Clolar™; Evoltra; NSC# 606,869; IND # 73,789; Novantrone

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
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

New York Medical College

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

New York Medical College

Valhalla, New York, United States

Levine Children's Hospital

Charlotte, North Carolina, United States

Countries

United States

References

Hochberg J, Oesterheld J, Gardenswartz A, Flower A, Klejmont L, Basso J, Shi Q, Harrison L, Borowitz MJ, Loken MR, Cairo MS. Mitoxantrone in combination with clofarabine (MITCL) in children, adolescents and young adults with relapsed/refractory acute leukaemia: final results of a phase I/II trial. EClinicalMedicine. 2025 Apr 28;83:103211. doi: 10.1016/j.eclinm.2025.103211. eCollection 2025 May.

Reference Type: DERIVED

PMID: 40641817 (View on PubMed)

Other Identifiers

L 10, 819

Identifier Type: OTHER

Identifier Source: secondary_id

NYMC 542

Identifier Type: -

Identifier Source: org_study_id