MRD/Risk-oriented Therapy of Adult Ph- ALL Including Pegylated Asparaginase and Lineage-targeted Methotrexate (LAL1913)

Gruppo Italiano Malattie EMatologiche dell'Adulto

Status and phase

Completed

Phase 2

Conditions

De Novo

Untreated Philadelphia Positive Acute Lymphoblastic Leukemia

Low-dose Corticosteroids Pretreatment

Secondary

Treatments

Drug: Cycle 7 Consolidation

Drug: Cycle 3 Early consolidation

Drug: Cycle 4 Consolidation

Drug: Cycle 6 Consolidation

Drug: Prephase PDN + CY

Drug: Cycle 1 Induction

Drug: Cycle 8 Reinduction

Drug: Maintenance

Drug: Cycle 5 Consolidation

Drug: Cycle 2 Induction / Early consolidation

Procedure: Allogeneic SCT or Autologous SCT

Study type

Interventional

Funder types

Other

Identifiers

NCT02067143

LAL1913

Details and patient eligibility

About

This study will be conducted in different centres and will study adult patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL). The study treatment will include a induction/consolidation therapy incorporating pegylated Asparaginase (Peg-ASP) and lineage-targeted high-dose methotrexate plus other antileukemic drugs, for the achievement of an early negative minimal residual disease (MRD) status. The MRD study supports a risk/MRD-oriented final consolidation phase.

Full description

The aim of this clinical study in adult ALL is to improve , by risk category, the overall disease-free survival in relation to the achievement of an early MRD negative status and following induction/consolidation with Peg-ASP, lineage-targeted methotrexate infusions and other disease-specific therapeutic elements, with or without the application of allogeneic or autologous SCT depending on risk class and MRD study results. A survey of severe infections occurring along the entire chemotherapy and stem cell transplant program and until 2 years from the achievement of CR will be performed with the aim to increase the knowledge of these complications and to evaluate their impact on the antileukemic program and on the long term outcome of the underlying malignancy. The prospective survey of severe infections will be performed as an ancillary observational objective of the present study.

Enrollment

204 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Signed written informed consent according to ICH/EU/GCP and national local laws.
Age 18-65 years.
A diagnosis of untreated Ph- ALL or LL is required, either de novo or secondary to chemo-radiotherapy for other cancer. Pretreatment with low-dose corticosteroids in patients presenting with hyperleukocytosis is allowed. All diagnostic procedures need to be performed on freshly obtained bone marrow (BM) and peripheral blood (PB) samples. The diagnosis must be one of: de novo ALL, secondary ALL, B-/T-cell LL Full cytological, cytochemical, cytogenetic and immunobiological disease characterization according to EGIL and WHO classifications. Bone marrow and peripheral blood sampling (ALL) or biopsy specimen (LL) are required for MRD study. Detailed indications on patient registration, storage of representative diagnostic material and diagnostic work-up, including the forwarding of samples for MRD study are given in Appendix B.
Bone marrow and peripheral blood sampling (ALL) or biopsy specimen (LL) for MRD study.
ECOG performance status 0-2, unless a performance of 3 is unequivocally caused by the disease itself and not by preexisting comorbidity, and is considered and/or documented to be reversible following the application of antileukemic therapy and appropriate supportive measures.

Exclusion criteria

Diagnosis of Burkitt's leukemia or lymphoma.
Down's syndrome
Pre-existing, uncontrolled pathology such as heart failure (congestive/ischemic, acute myocardial infarction within the past 3 months, untreatable arrhythmias, NYHA classes III and IV), severe liver disease with serum bilirubin >3 mg/dL and/or ALT >3 x upper normal limit (unless attributable to ALL), kidney function impairment with serum creatinine >2 mg/dL (unless attributable to ALL), and severe neuropsychiatric disorder that impairs the patient's ability to understand and sign the informed consent, or to cope with the intended treatment plan. N.B. For altered liver and kidney function tests, eligibility criteria can be reassessed at 24-96 hours, following the institution of adequate supportive measures.
Pre-existing HIV positive serology (i.e. already known before enrolment). If HIV positivity is detected after enrolment, the patient is sent off study.
A history of cancer that is not in a remission phase following surgery and/or radiotherapy and/or chemotherapy, with life expectancy <1 year.
Pregnancy declared by the patient herself, unless a decision is taken with the patient to induce a therapeutic abortion in order to carry on with ALL therapy. A pregnancy test is performed at diagnosis but does not preclude the enrolment into study. Fertile patients will be advised to adopt contraceptive methods while on treatment.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

204 participants in 1 patient group

Study population

Experimental group

Description:

In this phase II multicentric trial, eligible patients with Ph- ALL/LL will receive homogeneous supportive care and chemotherapy and will be homogeneously analyzed for response at prefixed timepoints from induction day 1. For risk-/MRD-oriented therapy, CR patients will be stratified by risk class according to diagnostic characteristics, MRD study and CT/PET (LL only) results during early consolidation.

Treatment: