Phase I Dose Escalation and Pharmacokinetics Clinical Trial of Mitoxantrone Hydrochloride Liposome in Children With Relapsed and Refractory Lymphoma and Solid Tumors

NCT05620862 | Active Not Recruiting Phase 1

• 1 other identifier: CSPC-DED-Ly -K01
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I dose escalation clinical trial: to explore the dose limiting toxicity (DLT) of mitoxantrone hydrochloride liposome injection in the treatment of children with relapsed and refractory lymphoma and solid tumors. Pharmacokinetics clinical trial: to observe the pharmacokinetics of mitoxantrone hydrochloride liposomes in children with relapsed and refractory lymphoma and solid tumors. To evaluate the safety and efficacy of mitoxantrone hydrochloride liposomes in children with lymphoma and solid tumors.

Conditions

Pediatric Solid Tumor

Outcome Measures

Primary Outcomes (6)

• Maximum-tolerated dose

  To investigate the safety and preliminary antitumor efficacy

  Up to 21 days

• peak time (Tmax)

  To evaluate the pharmacokinetics of mitoxantrone hydrochloride liposome at different doses in subjects

  Up to 18 weeks

• Maximum Plasma Concentration (Cmax)

  To evaluate the pharmacokinetics of mitoxantrone hydrochloride liposome at different doses in subjects

  Up to 18 weeks

• Area under the plasma concentration versus time curve (AUC)

  To evaluate the pharmacokinetics of mitoxantrone hydrochloride liposome at different doses in subjects

  Up to 18 weeks

• Elimination half life (t1/2)

  To evaluate the pharmacokinetics of mitoxantrone hydrochloride liposome at different doses in subjects

  Up to 18 weeks

• Incidence and severity of hematological adverse events

  To evaluate the incidence and severity of hematological adverse events in patients enrolled in phase Ib

  From date of randomization until 4 weeks after the last dose

Secondary Outcomes (6)

• Dose limiting toxicities

  Up to 21 days

• Objective response rate

  Up to 18 weeks

• Complete response rate

  Up to 18 weeks

• Progression free survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 70 weeks

• The incidence and severity of AE and SAE

  up to 42 weeks unless related serious adverse events need to be recorded indefinitely

Study Arms (1)

mitoxantrone hydrochloride liposome alone or combined with Irinotecan+Vincristine

EXPERIMENTAL

In phase Ia, patients with relapsed and refractory lymphoma and solid tumors will receive mitoxantrone hydrochloride liposome alone (at three doses of 16 mg/m2, 20 mg/m2 and 24 mg/m2, ) or combination of Irinotecan 50mg/ m2，d1-5, Vincristine 1.5mg/ m2，d1 for up to 6 cycles (21 days per cycle). In phase Ib, patients will recive mitoxantrone hydrochloride liposome 24 mg/m2, combination of Irinotecan 50mg/ m2，d1-5, Vincristine 1.5mg/ m2

Drug: Mitoxantrone Hydrochloride Liposome; Drug: Irinotecan; Drug: Vincristine

Interventions

Mitoxantrone Hydrochloride Liposome DRUG

In phase Ia, mitoxantrone hydrochloride liposome will be administered by an intravenous infusion at three doses of 16 mg/m2, 20 mg/m2 and 24 mg/m2 . In phase Ib, mitoxantrone hydrochloride liposome will be administered by an intravenous infusion of 24mg/m2. Up to 6 cycles (21 days per cycle)

mitoxantrone hydrochloride liposome alone or combined with Irinotecan+Vincristine

Irinotecan DRUG

50mg/ m2，d1-5, 21 days per cycle

mitoxantrone hydrochloride liposome alone or combined with Irinotecan+Vincristine

Vincristine DRUG

Vincristine 1.5mg/ m2，d1 , 21 days per cycle

mitoxantrone hydrochloride liposome alone or combined with Irinotecan+Vincristine

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \. Subjects fully understand and voluntarily participate in this study and sign the informed consent form (ICF);
• \. 2-21 years old;
• \. Expected survival ≥ 3 months;
• \. Subjects with histologically confirmed diagnosis of relapsed and refractory lymphoma and solid tumors, which is one of the following subtypes:
• Lymphoblastic lymphoma
• Anaplastic large T cell lymphoma
• Burkitt's lymphoma
• Diffuse large B-cell lymphoma
• Peripheral T, NK/T cell lymphoma
• Soft tissue sarcoma
• Neuroblastoma
• Other subtypes of lymphoma or solid tumors that the investigators believe can be included
• \. Relapsed lymphoma is defined as the lymphoma that relapse after obtaining complete response (CR) after initial chemotherapy; Refractory lymphoma subjects meet one of the following conditions: 1) The tumor shrinks \<50% or disease progression after 4 cycles of standard chemotherapy,; 2) CR after standard chemotherapy, but relapse within half a year; 3) 2 or more relapses after CR; 4) relapse after hematopoietic stem cell transplantation;
• \. Lymphoma subjects must have at least one evaluable or measurable lesion per lugano2014 criteria: for lymph node lesions, the length should be \> 1.5cm; For non-lymph node lesions, the length should be \> 1.0cm;
• \. Solid tumors must have tumor lesions measurable by CT or MRI;

You may not qualify if:

• \. The subject had previously received any of the following anti-tumor treatments:
• Subjects who have been treated with mitoxantrone or mitoxantrone liposomes;
• Previously received doxorubicin or other anthracycline treatment, and the total cumulative dose of doxorubicin was more than 360 mg/m2 (1 mg doxorubicin equivalent to 2 mg epirubicin);
• Subjects who received anti-tumor treatment (including chemotherapy, targeted therapy, glucocorticoid, traditional Chinese medicine with anti-tumor activity, etc.) or participated in other clinical trials and received trial drugs;
• Subjects who received autologous hematopoietic stem cell transplantation within 100 days after the first medication or allogeneic hematopoietic stem cell transplantation.
• \. Hypersensitivity to any study drug or its components;
• \. Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.);
• \. Heart function and disease meet one of the following conditions:
• Long QTc syndrome or QTc interval \> 480 ms;
• Complete left bundle branch block, grade II or III atrioventricular block;
• Serious and uncontrolled arrhythmias requiring drug treatment;
• New York Heart Association grade ≥ III;
• Cardiac ejection fraction (LVEF)\< 50%;
• A history of myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, a history of clinically serious pericardial disease, or ECG evidence of acute ischemia or active conduction system abnormalities within 6 months before recruitment.
• \. Hepatitis B and hepatitis C active infection (plus HBV DNA if one positive for hepatitis B surface antigen or core antibody and HBV DNA more than 1×103 copy/mL excluded; plus HCV RNA if hepatitis C antibody positive and HCV RNA more than 1×103 copy/mL exclude);

Sponsors & Collaborators

• Sun Yat-sen University: lead
• CSPC Ouyi Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Interventions

Irinotecan; Vincristine

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: November 8, 2022
• First Posted: November 17, 2022
• Study Start: October 25, 2022
• Primary Completion: September 1, 2024
• Study Completion: June 1, 2025
• Last Updated: July 9, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)