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

Precursor Cell Lymphoblastic Leukemia-Lymphoma Clinical Trial

Official title:

Non-intensive But Non-interruptive Treatment of Adult Ph-negative Acute Lymphoblastic Leukemia With Randomization for Maintenance or Autologous Hematopoietic Stem Cell Transplantation (HSCT) Followed by Maintenance in T-cell ALL Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03462095
• Other study ID #: ALL--2016
• Status: Recruiting
• Phase: N/A
• First received: March 6, 2018
• Last updated: March 12, 2018
• Start date: January 2017
• Est. completion date: December 1, 2022

Study information

• Verified date: March 2018
• Source: National Research Center for Hematology, Russia
• Contact: Elena N Parovichnikova, MD,PhD
• Phone: +79161252623
• Email: elenap[@]blood.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: December 1, 2022
• Est. primary completion date: December 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Procedure:
• Autologous HSCT
After the 3rd consolidation, T-cell ALL patients, randomized to auto-HSCT will be mobilised by G-SCF and harvested disregarding MRD-status. After completing the 5th consolidation T-ALL patients will be transplanted after non-myeloablative CEAM (CCNU, Ethoposide, ARA-C, Melphalan) conditioning, and after reconstitution will continue 2-years maintenance

Locations

Country	Name	City	State
Russian Federation	National Research Center for Hematology	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
National Research Center for Hematology, Russia

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival	Impact of autologous HSCT on DFS in T-cell ALL patients	5-years
Secondary	MRD-negativity after consolidation	Minimal Residual Disease clearance on non-intensive but non-interruptive treatment	6 months
Secondary	Overall survival	Impact of de-escalated approach on OS	5-years