A Study for Improving the Outcome of Childhood Acute Promyeloid Leukemia

NCT ID: NCT02200978

Last Updated: 2022-05-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 176 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2021-10-31

Brief Summary

Outcome of acute promyelocytic leukemia (APL) has greatly improved since the introduction of all-trans-retinoic acid (ATRA). Treatment with ATRA and anthracycline-based chemotherapy (ATRA + chemotherapy) decreases relapses of the disease as well as early hemorrhagic deaths. Nowadays patients with APL have an event-free survival (EFS) of up to 80%. However, there remains a subset of the patients in whom the disease relapses. Recently, a randomized prospective study showed that the addition of ATO to "ATRA + chemotherapy" treatment protocol had a significantly higher EFS in patients with APL than those treated with "ATRA + chemotherapy" protocol. The patients treated with "ATO + ATRA + chemotherapy" had a five years EFS of 89.2%. Moreover, a recent study showed that Indigo naturalis formula (RIF), a traditional Chinese medicine with tetraarsenic tetrasulfide (As4S4), indirubin, and tanshinone IIA as major active ingredients, yielded synergy in the treatment of a murine APL model in vivo and in the induction of APL cell differentiation in vitro . It is about 20 years since RIF was used to treat ALP in China. Clinical studies showed that this agent was effective against APL. Compared to ATO, RIF is relatively inexpensive and can be taken orally, resulting in reducing the number of hospital days and the treatment cost. However, there is no report comparing treatment outcomes of "ATO + ATRA + chemotherapy" and "RIF + ATRA + chemotherapy" protocols in children with APL so far. For this purpose, therefore, investigators are going to conduct a multicenter and randomized prospective study in children with APL.

Detailed Description

OBJECTIVES:

• Determine the safety and efficacy of "ATO/RIF + ATRA + less intensive chemotherapy" protocol in children with acute promyelocytic leukemia (APL).
• Compare the safety，efficacy and treatment cost of "RIF + ATRA + less intensive chemotherapy" with "ATO + ATRA + less intensive chemotherapy" protocol in children with APL. Determine if ATO can be substituted by RIF.

OUTLINE: This is a multicenter and randomized prospective study.

PROJECTED ACCRUAL: A total of 162 patients will be accrued for this study.

Conditions

Childhood Acute Promyelocytic Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ATO and chemotherapy

Induction:

ATRA 25mg/m2 d1-CR ≯42 days; ATO 0.16mg/kg d5-CR ≯42 days; mitoxantrone (MA) 10mg/m2 d3, or 7mg/m2 d2-4 (high risk).

Consolidation 1:

ATRA 25mg/m2 d1-15; MA 10mg/m2 d1-2; Intrathecal injection (IT)：Ara-C 15mg (age < 1 year), or 20 mg (1-3 years), or 30 mg ( > 3 years), dexamethasone 2mg.

Consolidation 2:

ATRA 25mg/m2 d1-15; ATO 0.16mg/kg d1-15; Ara-C 1g/m2 q12h d1-2 (high risk); IT.

Consolidation 3:

ATRA 25mg/m2 d1-15; ATO 0.16mg/kg d1-15; MA 10mg/m2 d1; Ara-C 1g/m2 q12h d1-2 (high risk); IT.

Maintenance:

① ATO 0.16mg/kg.d w1-2; ATRA 25mg/m2.d w1-2; MTX 20mg/m2 qw w3-12; 6MP 50mg/m2 qn w3-12. ② ATRA 25mg/m2.d w1-2; MTX 20mg/m2 qw w3-12; 6MP 50mg/m2 qn w3-12. Rotation between ① and ② until the end of maintenance.

Group Type: ACTIVE_COMPARATOR

ATO

Intervention Type: DRUG

Given IV

ATRA

Intervention Type: DRUG

Given orally

mitoxantrone

Intervention Type: DRUG

Given IV

Ara-C

Intervention Type: DRUG

Given IV

MTX

Intervention Type: DRUG

Given orally

6MP

Intervention Type: DRUG

Given orally

intrathecal injection

Intervention Type: OTHER

Ara-C and dexamethasone

RIF and chemotherapy

Induction:

ATRA 25mg/m2 d1-CR ≯42 days; RIF 0.135/kg d5-CR ≯42 days; mitoxantrone (MA) 10mg/m2 d3, or 7mg/m2 d2-4 (high risk).

Consolidation 1:

ATRA 25mg/m2 d1-15; MA 10mg/m2 d1-2; Intrathecal injection (IT)：Ara-C 15mg (age < 1 year), or 20mg (age 1-3 years), or 30mg (age > 3 years), dexamethasone 2mg.

Consolidation 2:

ATRA 25mg/m2 d1-15; RIF 0.135/kg d1-15; Ara-C 1g/m2 q12h d1-2 (high risk); IT.

Consolidation 3:

ATRA 25mg/m2 d1-15; RIF 0.135/kg d1-15; MA 10mg/m2 d1; Ara-C 1g/m2 q12h d1-2 (high risk); IT.

Maintenance:

① RIF 0.135/kg.d w1-2; ATRA 25mg/m2.d w1-2; MTX 20mg/m2 qw w3-12; 6MP 50mg/m2 qn w3-12. ② ATRA 25mg/m2.d w1-2; MTX 20mg/m2 qw w3-12; 6MP 50mg/m2 qn w3-12. Rotation between ① and ② until the end of maintenance treatment.

Group Type: EXPERIMENTAL

RIF

Intervention Type: DRUG

Given orally

ATRA

Intervention Type: DRUG

Given orally

mitoxantrone

Intervention Type: DRUG

Given IV

Ara-C

Intervention Type: DRUG

Given IV

MTX

Intervention Type: DRUG

Given orally

6MP

Intervention Type: DRUG

Given orally

intrathecal injection

Intervention Type: OTHER

Ara-C and dexamethasone

Interventions

ATO

Given IV

Intervention Type: DRUG

RIF

Given orally

Intervention Type: DRUG

ATRA

Given orally

Intervention Type: DRUG

mitoxantrone

Given IV

Intervention Type: DRUG

Ara-C

Given IV

Intervention Type: DRUG

MTX

Given orally

Intervention Type: DRUG

6MP

Given orally

Intervention Type: DRUG

intrathecal injection

Ara-C and dexamethasone

Intervention Type: OTHER

Other Intervention Names

As2O3; arsenic trioxide; Realgar-Indigo naturalis formula; all-trans retinoic acid; novantrone; cytarabine; cytosine arabinoside; methotrexate; mercaptopurine; IT

Eligibility Criteria

Inclusion Criteria

• Patients less than 16 years old with newly diagnosed PML-RARa positive acute promyelocytic leukemia.

Exclusion Criteria

• Patients who have coma, convulsion or paralysis due to intracranial hemorrhage or central nervous system leukemia at diagnosis.

• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

South China Children's Leukemia Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xue-Qun Luo, professor

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital, Sun Yat-Sen University

Locations

The First Affiliated Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, China

Countries

China

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: DERIVED

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Other Identifiers

2010001

Identifier Type: -

Identifier Source: org_study_id