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

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ClinicalTrials.gov Identifier: NCT05620862
Recruitment Status : Recruiting
First Posted : November 17, 2022
Last Update Posted : November 17, 2022
Sponsor:
Collaborator:
CSPC Ouyi Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Yizhuo Zhang, Sun Yat-sen University

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.


Condition or disease Intervention/treatment Phase
Lymphoma, Solid Tumors Drug: Mitoxantrone Hydrochloride Liposome Phase 1

Detailed Description:
This is a phase I dose escalation and pharmacokinetics clinical trial to evaluate the safety and efficacy of mitoxantrone hydrochloride liposomes in children with lymphoma and solid tumors. In the phase I dose escalation study 9-18 children with relapsed and refractory lymphoma and solid tumors will be treated with mitoxantrone hydrochloride liposome alone at the dose of 16 mg/m2, 20 mg/m2 and 24 mg/m2. Simultaneously 6~15 cases were added for pharmacokinetic study to ensure 8 cases are included in each dose group with the same mitoxantrone hydrochloride liposome dose.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Dose Escalation and Pharmacokinetics Clinical Trial of Mitoxantrone Hydrochloride Liposome in Children With Relapsed and Refractory Lymphoma and Solid Tumors
Actual Study Start Date : October 25, 2022
Estimated Primary Completion Date : June 1, 2024
Estimated Study Completion Date : June 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: mitoxantrone hydrochloride liposome
Children 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 for up to 6 cycles (21 days per cycle).
Drug: Mitoxantrone Hydrochloride Liposome
Mitoxantrone hydrochloride liposome will be administered by an intravenous infusion at three doses of 16 mg/m2, 20 mg/m2 and 24 mg/m2 for up to 6 cycles (21 days per cycle).




Primary Outcome Measures :
  1. Maximum-tolerated dose [ Time Frame: Up to 21 days ]
    To investigate the safety and preliminary antitumor efficacy

  2. peak time (Tmax) [ Time Frame: Up to 18 weeks ]
    To evaluate the pharmacokinetics of mitoxantrone hydrochloride liposome at different doses in subjects

  3. Maximum Plasma Concentration (Cmax) [ Time Frame: Up to 18 weeks ]
    To evaluate the pharmacokinetics of mitoxantrone hydrochloride liposome at different doses in subjects

  4. Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to 18 weeks ]
    To evaluate the pharmacokinetics of mitoxantrone hydrochloride liposome at different doses in subjects

  5. Elimination half life (t1/2) [ Time Frame: Up to 18 weeks ]
    To evaluate the pharmacokinetics of mitoxantrone hydrochloride liposome at different doses in subjects


Secondary Outcome Measures :
  1. Dose limiting toxicities [ Time Frame: Up to 21 days ]
    To investigate the safety

  2. Objective response rate [ Time Frame: Up to 18 weeks ]
    To investigate the preliminary antitumor efficacy of phase I dose escalation and pharmacokinetics study

  3. Complete response rate [ Time Frame: Up to 18 weeks ]
    To investigate the preliminary antitumor efficacy of phase I dose escalation and pharmacokinetics study

  4. Progression free survival [ Time Frame: 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 ]
    To investigate the preliminary antitumor efficacy of phase I dose escalation and pharmacokinetics study

  5. The incidence and severity of AE and SAE [ Time Frame: up to 42 weeks unless related serious adverse events need to be recorded indefinitely ]
    To identify the incidence and severity of AE and SAE (NCI CTCAE v5.0)



Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1. Subjects fully understand and voluntarily participate in this study and sign the informed consent form (ICF);
  • 2. 5-18 years old;
  • 3. Expected survival ≥ 3 months;
  • 4. Subjects with histologically confirmed diagnosis of relapsed and refractory lymphoma and solid tumors, which is one of the following subtypes:

    1. Lymphoblastic lymphoma
    2. Anaplastic large T cell lymphoma
    3. Burkitt's lymphoma
    4. Diffuse large B-cell lymphoma
    5. Peripheral T, NK/T cell lymphoma
    6. Soft tissue sarcoma
    7. Neuroblastoma
    8. Other subtypes of lymphoma or solid tumors that the investigators believe can be included
  • 5. 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;
  • 6. 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;
  • 7. Solid tumors must have tumor lesions measurable by CT or MRI;
  • 8. ECOG Performance Status: 0-2;
  • 9. Bone marrow function: Absolute neutrophil count ≥1.5×109/L, Platelet count ≥75×109/L, Hemoglobin ≥ 80g/L (Absolute neutrophil can be relaxed to ≥ 1.0×109/L, Platelet count can be relaxed to ≥50×109/L, Hemoglobin can be relaxed to ≥75 g/L in subjects with poor bone-marrow reserve);
  • 10. Liver and kidney function: serum creatinine ≤ 1.5×ULN (upper limit of normal); AST and ALT ≤ 2.5×ULN (≤ 5×ULN for subjects with liver metastases); total bilirubin ≤ 1.5×ULN (≤ 3×ULN for subjects with liver metastases).

Exclusion Criteria:

  • 1. The subject had previously received any of the following anti-tumor treatments:

    1. Subjects who have been treated with mitoxantrone or mitoxantrone liposomes;
    2. 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);
    3. 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;
    4. Subjects who received autologous hematopoietic stem cell transplantation within 100 days after the first medication or allogeneic hematopoietic stem cell transplantation.
  • 2. Hypersensitivity to any study drug or its components;
  • 3. Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.);
  • 4. Heart function and disease meet one of the following conditions:

    1. Long QTc syndrome or QTc interval > 480 ms;
    2. Complete left bundle branch block, grade II or III atrioventricular block;
    3. Serious and uncontrolled arrhythmias requiring drug treatment;
    4. New York Heart Association grade ≥ III;
    5. Cardiac ejection fraction (LVEF)< 50%;
    6. 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.
  • 5. 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);
  • 6. Human immunodeficiency virus (HIV) infection (HIV antibody positive);
  • 7. Subjects with other malignant tumors past or present (except for non-melanoma skin basal cell carcinoma, breast/cervical carcinoma in control, and other malignant tumors that have been effectively controlled without treatment within the past five years);
  • 8. Subjects suffering from primary or secondary central nervous system (CNS) lymphoma or a history of CNS lymphoma at the time of recruitment;
  • 9. Pregnant and lactating women and childbearing age patients unwilling to take contraceptive measures;
  • 10. Unsuitable subjects for this study determined by the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05620862


Contacts
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Contact: Yizhuo Zhang, PhD 020-87342460 zhangyzh@sysucc.org.cn

Locations
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China, Guangdong
Sun Yat-sen University Cancer Center Recruiting
Guangzhou, Guangdong, China, 510060
Contact: Yi-Zhuo Zhang, MD    18622221239    zhangyzh@sysucc.org.cn   
Principal Investigator: Yi-Zhuo Zhang, MD         
Sponsors and Collaborators
Sun Yat-sen University
CSPC Ouyi Pharmaceutical Co., Ltd.
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Responsible Party: Yizhuo Zhang, Director, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT05620862    
Other Study ID Numbers: CSPC-DED-Ly -K01
First Posted: November 17, 2022    Key Record Dates
Last Update Posted: November 17, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Mitoxantrone
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action