South China Children Cancer Group - Relapsed-Acute Lymphoblastic Leukemia 2022 Protocol

Study Overview
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Brief Summary
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In recent years, the prognosis of pediatric relapsed ALL patients has improved, but the 5-year OS of patients with first recurrence is still less than 50%. A number of in vitro studies have shown that arsenic trioxide (ATO) can selectively inhibit the growth and induce apoptosis in a variety of leukemia cell lines, suggesting that ATO as a synergist combined with other common chemotherapy drugs may provide a new target for the treatment of relapsed ALL. Realgar Indigo naturalis formula is a compound traditional Chinese medicine preparation developed in China. The main component of realgar is arsenic tetrasulfide (As4S4), which can produce similar pharmacological effects to ATO. Based on the R3 protocol, this study plans to perform a double-blind randomized controlled trial, and to randomly combine compound Huangdai tablets with compound Huangdai tablets in the treatment of intermediate and high risk ALL children, in order to improve the MRD negative rate after induction therapy in this group of children, which may provide a new method for the clinical treatment of relapsed ALL.

Detailed Description
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In recent years, the prognosis of pediatric relapsed ALL patients has improved, but the 5-year OS of patients with first recurrence is still less than 50%, and the prognosis of children with intermediate and high risk is even worse, so there is an urgent need to explore new and effective treatment methods. A number of in vitro studies have shown that arsenic trioxide (ATO), which is safe and effective in the treatment of APL, can selectively inhibit the growth and induce apoptosis in a variety of leukemia cell lines, suggesting that ATO as a synergist combined with other common chemotherapy drugs may provide a new target for the treatment of relapsed ALL. Realgar Indigo naturalis formula is a compound traditional Chinese medicine preparation developed in China. The main component of realgar is arsenic tetrasulfide (As4S4), which can produce similar pharmacological effects to ATO. The UK ALL R3 protocol is an advanced and mature clinical trial. The results showed that the MRD negative rate after induction chemotherapy and the 2-year DFS of traditional chemotherapy ±HSCT in children with intermediate and high risk did not reach 50%. Based on the R3 protocol, this study plans to perform a double-blind randomized controlled trial, and to randomly combine compound Huangdai tablets with compound Huangdai tablets in the treatment of intermediate and high risk ALL children, in order to improve the MRD negative rate after induction therapy in this group of children, which may provide a new method for the clinical treatment of relapsed ALL.

Official Title
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South China Children Cancer Group - Relapsed-Acute Lymphoblastic Leukemia 2022 Protocol

Conditions
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Arsenic Trioxide, Childhood ALL

Intervention / Treatment
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* Drug: Realgar Indigo naturalis formula
* Combination Product: Conventional chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: B or T cell type; the first recurrence; the risk stratification was medium or high risk. Exclusion Criteria: mature B cell leukemia; acute mixed phenotype leukemia; patients with positive BCR/ABL fusion gene; the second tumor definite CML blast crisis; ALL with Down's syndrome.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>Oral placebo was added to conventional chemotherapy | Combination Product: Conventional chemotherapy<br>* conventional chemotherapy<br>|
| Experimental: Experimental Group<br>Oral RIF was added to conventional chemotherapy | Drug: Realgar Indigo naturalis formula<br>* Realgar Indigo naturalis formula was used in the induction, consolidation and intensive treatment of patients in intermediate or high risk<br>* Other names: RIF;Combination Product: Conventional chemotherapy<br>* conventional chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate | Complete response rate after induction treatment in two groups | from diagnosis, an average of 7 weeks |