MRD-associated Non-intensive But Non-interruptive Treatment of Ph-negative Acute Lymphoblastic Leukemia Adult Patients

Multicenter Prospective Study of Safety and Efficacy MRD-associated Non-intensive But Non-interruptive Treatment of Ph-negative Acute Lymphoblastic Leukemia Adult Patients

Non-intensive But Non-interruptive Treatment based on previously study RALL-2016 of Adult Ph-negative Acute Lymphoblastic Leukemia: 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 remission (CR) with MRD-positive status after 2nd induction receive consolidation 1-3 with venetoclax (56 days), and B-ALL patients in complete remission (CR) with MRD-positive status after 2nd induction receive 1 consolidation with blinatumomab. After that consolidation bone samples are collected and tested for MRD and patients will continue therapy by protocol without HSCT if MRD-negative (by flow cytometry by aberrant immunophenotype in a centralized lab) status was achieved.

Study Overview

• Status: Recruiting
• Conditions: Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Intervention / Treatment: Drug: blinatumomab for B-ALL, venetoclax for T-ALL

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 and B-ALL patients are being study MRD (by FCM) MRD-positive patients with T-ALL will receive 1-3 consolidation with venetoclax (400 mg/d), and B-ALL patients will receive1 additional consolidation by blinatumomab
• Non-interruptive 5 consolidation phases with dose modification according to WBC and platelets count after CR achievement. Rotation of consolidation is permitted
• 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 allo-HSCT
• Allo-HSCT is planned only for very high risk patients (11q23 ALL, MRD positivity after target therapy, ETP T-ALL)

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Olga Aleshina, MD, PhD; Phone Number: +79629745058; Email: dr.gavrilina@mail.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Recruiting
    • Olga Aleshina
    • Contact: Olga Aleshina; Phone Number: +79629745058

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age 18-55 years old of patient,

- Clinical diagnosis of non-treated Ph-negative ALL

Exclusion Criteria:

• age more than 55 years old,

• Clinical diagnosis of Ph-positive ALL
• Clinical diagnosis of relapsed/refractory ALL,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MRD-positive with Target therapy; MRD-positive patients after induction therapy in target therapy group (for B-ALL- blinatumomab, for T-ALL - venetoclax+ChT)	Drug: blinatumomab for B-ALL, venetoclax for T-ALL; MRD-associated based therapy for Ph-negative acute lymphoblastic leukemia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	Rate of Diseases-free survival in MRD-positive ALL patients	3-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRD-negativity after target therapy	Rate of Minimal Residual Disease negativity after target therapy	1 month
Overall survival	Rate of overall survival in protocol	3-yaers OS

Collaborators and Investigators

• Sponsor: National Research Center for Hematology, Russia
• Investigators: Study Director: Elena Parovichnikova, MD, PhD, National Research Medical Center for Hematology

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: January 3, 2024
• First Submitted That Met QC Criteria: January 31, 2024
• First Posted (Estimated): February 1, 2024

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Antineoplastic Agents; Venetoclax; Blinatumomab
• Other Study ID Numbers: RALL-2016m

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No