Azacitidine and Homoharringtonine in JMML

Efficacy of Concomitant Use of Azacitidine and Homoharringtonine in Children With Juvenile Myelomonocytic Leukemia

Juvenile myelomonocytic leukemia (JMML) has a poor prognosis in general, with hematopoietic stem cell transplant (HSCT) remaining the standard of care for cure. Azacitidine and homoharringtonine, which exhibited a anticancer mechanism and has been widely used in patients with relapse/refractory acute myeloid leukemia (AML). However, the efficacy of these agents has not been elucidated in children with JMML. The primary objective is to assess the treatment effect on response rate in this subject population.

Study Overview

• Status: Recruiting
• Conditions: JMML
• Intervention / Treatment: Drug: Azacitidine and homoharringtonine

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wen-Yu Yang, M.D.; Phone Number: +86-22-23909138; Email: yangwenyu@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Institute of hematology & blood diseases hospital, chinese academy of medical sciences & peking union medical college
      • Contact: Xiao-Fan Zhu, M.D.; Phone Number: +86-22-23909001; Email: xfzhu@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newly diagnosed JMML, with PB and BM confirming diagnosis prior to informed consent signature, with one of the following:

  1. somatic mutation in PTPN11
  2. somatic mutation in KRAS
  3. somatic mutation in NRAS and HbF % > 5x normal value for age
  4. clinical diagnosis of neurofibromatosis Type 1.

Exclusion Criteria:

• 1. Any condition that would prevent the subject from participating in the study.

  2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if participated in the study.

  3. Any condition that confounds the ability to interpret data from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group	Drug: Azacitidine and homoharringtonine; Concommitant use of azacitidine and homoharringtonine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Juvenile Myelomonocytic Leukemia (JMML) response rate at end of 4 Months	Defined as proportion of patients with sustained clinical complete remission [cCR] or clinical partial remission [cPR] according to the International JMML response criteria in Niemeyer 2014 at 3 months (28 days cycles). Response must be sustained for at least 4 weeks either in the 4-week period preceding or succeeding 3 months (ie, sustained over the period minimum 2 months to end of 3 months, or end of 3 months to end of 4 months).	Up to 4 Months

Collaborators and Investigators

• Sponsor: Air Force Military Medical University, China
• Collaborators: The Second Hospital of Hebei Medical University; Qilu Hospital of Shandong University; The Affiliated Hospital of Qingdao University; Children's Hospital of Hebei Province; Taian City Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: August 6, 2020
• First Submitted That Met QC Criteria: August 6, 2020
• First Posted (Actual): August 10, 2020

Study Record Updates

• Last Update Posted (Actual): August 10, 2020
• Last Update Submitted That Met QC Criteria: August 6, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Protein Synthesis Inhibitors; Azacitidine; Homoharringtonine
• Other Study ID Numbers: JMML-CAMS-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No