Treatment of Breakpoint Cluster Region-Abelson (BCR-ABL) Negative ALL in Adults

Study Overview
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Brief Summary
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After consolidation therapy adult patients (≥18 yr) with Ph-negative ALL will be treated with continuation chemotherapy or allogeneic hematopoietic stem cell transplantation (alloHSCT) according to both measurable residual disease (MRD) and results of genetic study performed at baseline.

Detailed Description
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Patients will be uniformly treated with four drug-induction: vincristine (VCR), prednisone (PDN), pegylated asparaginase (PegASP), daunorubicin (DNR). Resistant patients will receive a second induction with fludarabine, Ara-C, G-Colony-Stimulating Factor (G-CSF) and idarubicin (FLAG-IDA). Patients with adequate MRD clearance after induction will receive 3 blocks of early consolidation. If adequate MRD clearance and good genetic background, the patients will proceed to delayed intensification, reinduction and maintenance. The remaining patients will receive early or delayed alloHSCT.

Official Title
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Treatment of BCR-ABL Negative ALL in Adults According to MRD and Genetics

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Pediatric-type of chemotherapy
* Procedure: allogeneic HSCT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18-60 yr with de novo Ph-neg ALL Eastern Cooperative Oncology Group (ECOG) 0-2 (or >2 if due to ALL) Informed consent Exclusion Criteria: Mature B-ALL, Ph+ ALL or blast crisis of chronic myeloid leukemia (CML), ALL of ambiguous lineage ECOG >2 not due to ALL Impaired cardiac, respiratory, hepatic or renal function not due to ALL Pregnancy HIV positivity Severe psychiatric disease Negative to sign informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: CHEMOTHERAPY<br>Pediatric-type of chemotherapy | Drug: Pediatric-type of chemotherapy<br>* Pediatric type chemotherapy (induction, early and delayed consolidation, reinduction, maintenance). Induction (VCR,PDN,PegASP,DNR). Early and delayed consolidation (high-dose Methotrexate, high-dose Cytarabine, PegASP). Reinduction (VCR, PDN, PegASP, DNR). Maintenance (Methotrexate, Mercaptopurine)<br>|
| Other: allogeneic HSCT<br>allogeneic HSCT | Procedure: allogeneic HSCT<br>* allogeneic HSCT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Time from diagnosis to death or last follow-up | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission (CR) rate | Proportion of patients who achieve CR with or 2 induction therapy lines | 4 or 8 weeks after treatment onset | 
| MRD status after induction and consolidation | Proportion of patients who achieve and maintain the negative MRD status (<10-4) | After induction (4-8 weeks) and consolidation (16-20 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALL, adult, Ph-negative, minimal residual disease, transplantation