Treateament of Newly Diagnosed Acute Monocytic Leukemia in Children (SCCLG-M5)

July 25, 2023 updated by: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Treateament of Newly Diagnosed Acute Monocytic Leukemia in Children： A Prospective Multicenter Study in South China

This is a multicenter, single arm, prospective, intervention trial. Since cladribine can enhance the biological activity and self-protection of cytarabine, giving cladribine and cytarabine together may kill more cancer cells. 10 centers from South China Childhood Leukaemia Collaborative Group carry out the SCCLG-M5-2022 regimen including two courses of CLAG(cladribine, darubicin and cytarabine) in the induction period for the treatment of newly dignosed acute monocytic leukemia (M5). The targeted drugs sorafenib is used for FLT3 positive acute monocytic leukemia to inhibit the serine / threonine kinase activity of FLT3.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES

1.To study the 3 year-overall survival of newly diagnosed monocytic leukemia treated with Cladribine and cytarabine in children.

SECONDARY OBJECTIVES

  1. To describe the complete response rate following CLAG (cladribine, cytarabine and granulocyte stimulating factor) in newly diagnosed monocytic leukemia in children for intensive induction therapy.
  2. To evaluate the 3-year progression-free survival in response to CLAG in children.
  3. To assess the toxicity of CLAG including cumulative infection incidence, cumulative adverse effects and chemotherapy-related mortality (TRD).
  4. To study the progression-free survival and overall survival (1 year, 2 year and 3 year) of newly diagnosed monocytic leukemia with positive FLT3 treated with CLAG in children and the side effects of sorafenib.

OUTLINE:

  1. The induction phase includes two parts including induction therapy I(CLAG) and induction therpay II(CLAG+I/M).

  2. The diagnosis and classified criteria is according to the 2016 WHO classification criteria for hematopoietic and lymphoid tissue tumors, and the consolidation therapy consists the therapeutic phases as the NOPHO-AML 2004 protocol prescribed.

    INDUCTION THERAPY I: Patients receive cladribine intravenously (IV) at a dose of 5mg/m2/day combined with cytarabine 2g/m2/day on day 1-5 and granulocyte stimulating factor 5ug/kg/day on day 0-6. When blood count recover(WBC>2.0×109/L， ANC1.0×109/L、PLT≥50×109/L) , Patients achieving a morphological leukemia free state (< 5% blasts) or MRD< 1% receive a second course treatment as above.

    INDUCTION THERPAY II: Patients receive cladribine intravenously (IV) at a dose of 5mg/m2/day combined with cytarabine 2g/m2/day on day 1-5, mitoxantrone/idarubicin 10mg/m2/day on day 1-3 and granulocyte stimulating factor 5ug/kg/day on day 0-6. Patients achieving blast count≥5% or MRD ≥1% proceed to induction II therpy.

  3. For FLT3 positive acute monocytic leukemia children, sorafenib 200mg/m2/day was taken orally until molecular biology remission for 2 years.
  4. After two courses of indution phase, patients with incomplete response（MRD≥0.1%）are recommended into hematopoietic stem cell transplantation.
  5. After two courses of indution phase, patients with persisting positive adverse prognosis cytogenetic abnormalities are recommended into hematopoietic stem cell transplantation.

Patients must meet one of the following risk criteria:

Standard-risk (SR) group meeting all of the following criteria:

Initial WBC < 10,000/μL

M1 (<5%) blasts or MRD<1% in bone marrow after the first course of induction therapy

M1 (<5%) blasts or MRD<0.1% in bone marrow after two courses of induction therapy

Cytogenetic abnormalities with good prognosis

Intermediate-risk (IR) group meeting the following criteria:

Lack of low-risk and high-risk conditions

High-risk (HR) group meeting ≥ 1 of the following criteria:

M2/M3(≥5%) blasts or MRD>5% in bone marrow after the first course of induction therapy

MRD≥0.1% in bone marrow after two course of induction therapy

Cytogenetic abnormalities with poor prognosis

Study Type

Interventional

Enrollment (Estimated)

43

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Foshan, Guangdong, China
        • Recruiting
        • Maternal and Child Health Hospital of Foshan
        • Contact:
      • Guangzhou, Guangdong, China
        • Recruiting
        • The First Affiliated Hospital of Guangzhou Medical University
        • Contact:
      • Guangzhou, Guangdong, China
        • Recruiting
        • Zhujiang Hospital of Southern Medical University
        • Contact:
      • Guangzhou, Guangdong, China
        • Recruiting
        • Guangzhou First People's Hospital
        • Contact:
      • Guangzhou, Guangdong, China
        • Recruiting
        • Third Affiliated Hospital, Sun Yat-Sen University
        • Contact:
      • Shantou, Guangdong, China
        • Recruiting
        • Guangzhou First People's Hospital First Affiliated Hospital of Shantou University Medical College
        • Contact:
    • Hunan
      • Changsha, Hunan, China
        • Recruiting
        • Second Xiangya Hospital of Central South University
        • Contact:
    • Jiangxi
      • Nanchang, Jiangxi, China
        • Recruiting
        • The First Affiliated Hospital of Nanchang University
        • Contact:
      • Nanchang, Jiangxi, China
        • Recruiting
        • Jiangxi Province Children's Hospital Southern Medical University, China
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 14 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

0-14 years old

Cytologically proven acute monocytic leukemia (M5) with other treatment

Exclusion Criteria:

Secondary to immunodeficiency or MDS

Second tumor

Dowm's syndrome

Evolution of chronic myelogenous leukemia to blast crisis

Death or quit treatment in seven days at the begining of induction therapy

Treatment with other effective chemotherapy drugs for AML, excluding the low dose chemotherapy for the purpose of reducing leukocytes in hyperleukocytic leukemia

Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled heart, brain, liver and kidney failure etc.)

Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: treatment arm

The patients in this arm will receive SCCLG-M5 2022 regimen for newly dignosed acute monocytic leukemia (M5) ,including two courses of CLAG(cladribine, darubicin and cytarabine) in the induction period and followed by three courses(HA1M, HA2E, HA3) in consolidation therapy prescribed as the NOPHO-AML 2004 protocol.

The targeted drugs sorafenib 200mg/m2/day orally is used for FLT3 positive acute monocytic leukemia until molecular biology remission for 2 years.
Drug: Cladribine
5mg/㎡/day d1-5 in 2 hours, before the use of Cytarabine
Other Names:
  • cladribine injection
Drug: G-CSF
5ug/kg/day d0-5,if Peripheral blood leukocytes<20,000/ul
Other Names:
  • granulocyte
Drug: Cytarabine
2g/㎡/day d1-5 in 4 hours, after the use of Cladribine
Other Names:
  • Ara-C
Drug: Idarubicin
Idarubicin 10mg/m2/day or mitoxantrone 10mg/m2/day on day 1-3 in the induction therapy II
Other Names:
  • Idamycin
  • IDA
Drug: Mitoxantrone
Idarubicin 10mg/m2/day or mitoxantrone 10mg/m2/day on day 1-3 in the induction therapy II
Other Names:
  • MIT
Drug: Sorafenib
200mg/m2/day was taken orally until molecular biology remission for 2 years
Other Names:
  • Nexavar
  • sorafenib tosylate
  • sorafinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 3 years
TOS was defined as time from diagnostic date through the date of death due to any reasons. For all other participants, the last follow-up available was taken as the last control. If the participant had not completed the study, the date of the last visit available was considered.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Induced remission rate (CR)
Time Frame: 3 years
According to the time point specified in the treatment plan (22 days after the end of induction I, 29-43 days after the end of induction II and before each consolidation scheme) bone marrow puncture and lumbar puncture were performed. The follow-up contents included the detection of the count of primitive / immature lymphocytes and flow MRD. If there was a positive gene at the onset, the quantitative monitoring of the gene should be performed as MRD data at the same time. If the gene cannot be analyzed quantitatively, PCR qualitative analysis should still be performed as the monitoring basis
3 years
Safety,including cumulative infection incidence, adverse reaction and chemotherapy-related mortality (TRD)
Time Frame: 3 years
During treatment, closely monitor relevant laboratory tests, register adverse reaction records, and report the records according to the requirements of CRF form.
3 years
Event-free survival (EFS)
Time Frame: 3 years
EFS was estimated from date of diagnosis until date of one of the following events: relapse, refractory disease, second malignancy or death from any reason.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Collaborators

The First Affiliated Hospital of Nanchang University
Guangzhou First People's Hospital
The First Affiliated Hospital of Guangzhou Medical University
Third Affiliated Hospital, Sun Yat-Sen University
Second Xiangya Hospital of Central South University
Southern Medical University, China
First Affiliated Hospital of Shantou University Medical College
Jiangxi Province Children's Hospital
Maternal and Child Health Hospital of Foshan

Investigators

  • Study Chair: dunha zhou, M.D, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2021

Primary Completion (Estimated)

March 30, 2026

Study Completion (Estimated)

March 30, 2026

Study Registration Dates

First Submitted

December 26, 2021

First Submitted That Met QC Criteria

March 28, 2022

First Posted (Actual)

April 6, 2022

Study Record Updates

Last Update Posted (Actual)

July 27, 2023

Last Update Submitted That Met QC Criteria

July 25, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-KY-052
  • 2021A1515011809 (Other Grant/Funding Number: Province natural science fund of Guangdong)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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