Clinical trial NCT05313958: Treateament of Newly Diagnosed Acute Monocytic Leukemia in Children
Official title: Treateament of Newly Diagnosed Acute Monocytic Leukemia in Children： A Prospective Multicenter Study in South China
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Leukemia, Monocytic, Acute
Pediatric AML
Keywords: Acute monocytic leukemia
pediatric
Cladribine
sorafenib
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Third Affiliated Hospital, Sun Yat-Sen University
name: Maternal and Child Health Hospital of Foshan
name: The First Affiliated Hospital of Guangzhou Medical University
name: Second Xiangya Hospital of Central South University
name: Jiangxi Province Children's Hospital
name: Southern Medical University, China
name: The First Affiliated Hospital of Nanchang University
name: Guangzhou First People's Hospital
name: First Affiliated Hospital of Shantou University Medical College
First posted: 2022-04-06
Enrollment: 43
Sex: ALL
Minimum age (years): 1
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival (OS)
timeFrame: 3 years
Secondary outcomes:
measure: Induced remission rate (CR)
timeFrame: 3 years
measure: Safety,including cumulative infection incidence, adverse reaction and chemotherapy-related mortality (TRD)
timeFrame: 3 years
measure: Event-free survival (EFS)
timeFrame: 3 years
Other outcomes:
Locations:
city: Foshan
country: China
facility: Maternal and Child Health Hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Third Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Shantou
country: China
facility: Guangzhou First People's Hospital First Affiliated Hospital of Shantou University Medical College
state: Guangdong
city: Changsha
country: China
facility: Second Xiangya Hospital of Central South University
state: Hunan
city: Nanchang
country: China
facility: Jiangxi Province Children's Hospital Southern Medical University, China
state: Jiangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: dunha zhou, M.D
role: STUDY_CHAIR
References:
citation: Liu LP, Zhang AL, Ruan M, Chang LX, Liu F, Chen X, Qi BQ, Zhang L, Zou Y, Chen YM, Chen XJ, Yang WY, Guo Y, Zhu XF. Prognostic stratification of molecularly and clinically distinct subgroup in children with acute monocytic leukemia. Cancer Med. 2020 Jun;9(11):3647-3655. doi: 10.1002/cam4.3023. Epub 2020 Mar 26.
citation: Weis TM, Marini BL, Bixby DL, Perissinotti AJ. Clinical considerations for the use of FLT3 inhibitors in acute myeloid leukemia. Crit Rev Oncol Hematol. 2019 Sep;141:125-138. doi: 10.1016/j.critrevonc.2019.06.011. Epub 2019 Jun 28.
citation: Rubnitz JE, Crews KR, Pounds S, Yang S, Campana D, Gandhi VV, Raimondi SC, Downing JR, Razzouk BI, Pui CH, Ribeiro RC. Combination of cladribine and cytarabine is effective for childhood acute myeloid leukemia: results of the St Jude AML97 trial. Leukemia. 2009 Aug;23(8):1410-6. doi: 10.1038/leu.2009.30. Epub 2009 Feb 26.