De-escalated Treatment Approach for Adult Ph-negative Acute Lymphoblastic Leukemia (ALL)

Not Applicable

• Conditions: Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Interventions: Procedure: Autologous HSCT

• Registration Number: NCT03462095
• Lead Sponsor: National Research Center for Hematology, Russia

Brief Summary

No high-dose methotrexate (MTX) and high-dose cytarabine (ARA-C) consolidation blocks, L-asparaginaseis scheduled for 1 year of treatment, 21 intrathecal injections through the whole treament, T-ALL patients in complete remossion (CR) after the informed consent are randomized to: auto-HSCT vs no auto-HSCT, - with the similar further maintenance. Stem cell harvest is performed after the 3rd consolidation by G-SCF disregarding minimal residual disease (MRD) level. Auto-HSCT is planned after the 5th consolidation phase. All primary bone samples are collected and tested for cytogenetics and molecular markers, all included patients are monitored by flow cytometry by aberrant immunophenotype in a centralized lab.

Detailed Description

* 7 days prednisolone prephase

* 8 weeks induction with de-escalation of induction chemotherapy: 3 instead of 4 dauno/vncr pulses,

1. instead of 2 Cph injections during induction,

2. instead of 4 ARA-C blocks, distribution of of L-asp injections through all phases

* After CR achievement T-cell ALL patients are being randomized to auto-HSCT vs no auto-HSCT

* Non-interruptive 5 consolidation phases with dose modification according to WBC and platelets count after CR achievement. Rotation of consolidation is permitted

* After the 3rd consolidation stem cells harvesting is carried out for T-cell ALL patients randomized to auto-HSCT

* Auto-HSCT after the 5th consolidation phase with non-myeloablative CEAM conditioning

* 2 years maintenance for all patients

* 21 TIT through the whole treatment with higher intensity during induction\|consolidation

* Centralized MRD monitoring at +70 d, + 133 d, + 190 days; before and after auto-HSCT

* Allo-HSCT is planned only for very high risk patients (11q23 ALL, MRD positivity at day +190)

Study Timeline

• Study Start: 2017-01
• Status Verified: 2018-03
• Study First Submitted: 2018-03-06
• Study First Submitted QC: 2018-03-06
• Study First Posted: 2018-03-12
• Last Update Submitted: 2018-03-12
• Last Update Posted: 2018-03-13
• Primary Completion: 2019-12-01
• Study Completion: 2022-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

• age 18-55 yy, newly diagnosed non-treated Ph-negative ALL

Exclusion Criteria

• age > 55 yy, Ph-positivity, relapsed|refractory ALL, pretreated ALL

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Auto-HSCT	Autologous HSCT	After completing prolonged consolidation T-cell ALL patients will get autologous HSCT followed by 2 years maintenance

Primary Outcome Measures

Name	Time	Method
Disease-free survival	5-years	Impact of autologous HSCT on DFS in T-cell ALL patients

Secondary Outcome Measures

Name	Time	Method
MRD-negativity after consolidation	6 months	Minimal Residual Disease clearance on non-intensive but non-interruptive treatment
Overall survival	5-years	Impact of de-escalated approach on OS

Trial Locations

Locations (1)

National Research Center for Hematology; 🇷🇺 Moscow, Russian Federation