Personalized Therapy of Precursor Lymphoid Neoplasms

Study Overview
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Brief Summary
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The primary goal of this study by The Polish Adult Leukemia Group (PALG) is to verify if individual therapeutic approach taking into account biological and phenotypic differences as well as response at the level of minimal residual disease is associated with improved outcome of adults with precursor lymphoid neoplasms

Detailed Description
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Between 1997-2010 the PALG run three prospective studies. In the most recent PLAG 5-2007 protocol attempts have been made to individualize treatment. In particular, stratification to high and standard risk group was based on both conventional clinical criteria and the level of MRD after induction and consolidation. Patients with unsatisfactory response were referred for allogeneic hematopoietic stem cell transplantation (alloHSCT). Interim analysis showed significant improvement compared to previous PALG 4-2002 protocol with regard to both overall survival and leukemia-free survival. The reasons of failure were relapses and non-relapse mortality (NRM) associated with alloHSCT. In the current protocol we intend to further adjust the therapy for individual patients needs. We assume that this way we will be able to reduce the risk of relapse and NRM and improve the cure rate. All patients will receive multiagent induction and consolidation chemotherapy. The type and intensity of the therapy, as well as indications for allogeneic and autologous HSCT will depend on age, status of MRD, immunophenotype and the presence of BCR/ABL fusion gene.

Official Title
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Optimization of the Treatment of Adults With Precursor Lymphoid Neoplasms With Adjustment of the Type and Intensity of the Therapy for Age, Status of Minimal Residual Disease, Genetic and Phenotypic Features

Conditions
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Precursor Lymphoid Neoplasms

Intervention / Treatment
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* Other: Treatment strategy: induction, consolidation, HSCT, maintenance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: New diagnosis of PLN according to WHO 2008 classification Age ≥18 years Biological status allowing administration of induction therapy Informed patient consent form signed Exclusion Criteria: Pregnancy Psychiatric diseases History of other malignancies HIV infection Active hepatitis Hypersensitivity to drugs used in induction

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multiagent induction-consolidation<br>Induction, consolidation, HSCT, maintenance for adults with newly diagnosed precursor lymphoid neoplasms | Other: Treatment strategy: induction, consolidation, HSCT, maintenance<br>* Patients <55 years Ph-neg.: induction (daunorubicin, prednisone, vincristin, PEG-asparaginase), 2nd induction (if non-remission or MRD>0.1%; FLAM, MiniFLAM or FLAM-CAMP dependent on age and phenotype), consolidation (methotrexate, etoposide, cytarabine, cyclophosphamide, PEG-asparaginase). If MRD <0.01%: autoHSCT + maintenance (mercaptopurine, methotrexate) or multiagent maintenance (additionally daunorubicin, vincristin, prednisone); remaining patients: alloHSCT. Prophylaxis of leptomeningeal involvement: liposomal cytarabine intrathecally. Patients >55 years, Ph-neg.: as above, reduced doses. AlloHSCT with reduced conditioning. Patients Ph-pos.: as above, reduced doses in combination with continues imatinib. All intended for alloHSCT.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | three years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leukemia-free survival |  | three years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute lymphoblastic leukemia, Induction, Consolidation, Minimal residual disease, Hematopoietic stem cell transplantation