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

• Sponsor: National Research Center for Hematology, Russia (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03462095
• Collaborator: (none)
• Enrollment: 350
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 71
• Patients Per Site Per Month: 4.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Precursor Cell Lymphoblastic Leukemia-Lymphoma	Procedure: Autologous HSCT	N/A

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 350 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jan 1, 2017
• Anticipated Primary Completion Date: Dec 1, 2019
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: no Auto-HSCT After completing prolonged consolidation T-cell ALL patients will continue with 2 years maintenance
Experimental: Auto-HSCT After completing prolonged consolidation T-cell ALL patients will get autologous HSCT followed by 2 years maintenance	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

Outcome Measures

Primary Outcome Measures

1. Disease-free survival [5-years]

   Impact of autologous HSCT on DFS in T-cell ALL patients

Secondary Outcome Measures

1. MRD-negativity after consolidation [6 months]

   Minimal Residual Disease clearance on non-intensive but non-interruptive treatment

2. Overall survival [5-years]

   Impact of de-escalated approach on OS

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Research Center for Hematology	Moscow		Russian Federation	125167

Sponsors and Collaborators

• National Research Center for Hematology, Russia

Investigators

• Study Director: Valeriy V Savchenko, Academician, National Research Center for hematology, Moscow, Russia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Research Center for Hematology, Russia
• ClinicalTrials.gov Identifier: NCT03462095
• Other Study ID Numbers: ALL--2016
• First Posted: Mar 12, 2018
• Last Update Posted: Mar 13, 2018
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid

Study Results

No Results Posted as of Mar 13, 2018