Treatment Protocol for Newky Diagnosed Adult Ph Positive ALL

Summary

The goal of this prospective, multicenter, open observational study is to assess the efficacy and safety of the treatment for acute lymphoblastic leukemia Ph' positive adult patients with approved combinations of chemotherapy and tyrosine kinase inhibitor (TKI).

Efficay refers to the rate of Complete Molecular Response (BCR::ABL1/ABL1 ratio 0.01%) in eah treatment arm. Safety refers to measurement of i) Adverse events (AEs) and serious adverse events (SAEs) according to standard clinical and laboratory tests (hematology and chemistry, physical examination, vital sign measurements, and diagnostic tests), ii) incidence and degree of cytopenias and iii) incidence and degree of infections.

Low-dose chemotherapy will be given together with the TKI imatinib to patients of all ages as induction to remission phase.

Consolidation treatment will continue with low-dose chemotherapy with imatinib if the patient fullfills both criteria: to show a measurable residual disease (MRD) value lower than 0,01% at 3 month of therapy, and not showing IKZF1plus genetics Those patients have any of these 2 conditions will be considered high-risk patients and will recieve consolidation treatment intensification with low-dose chemotherapy plus ponatinib as TKI and allogeneic stem cell transplantation (allo SCT). The remaining patients (standard-risk) will receive maintenance chemotherapy together with imatinib or ponatinib and will not be submitted to alloSCT.

Conditions

• Lymphoblastic Leukemia
• Philadelphia-Positive ALL
• Adult ALL

Interventions

DRUG

Vincristine

dose 1.5 mg/m2 at days 1, 8, 15 and 22

DRUG

Dexamethasone

40 mg on days 1-2, 8-9,15-16 and 22-23

DRUG

Imatinib

600 mg per day from 1 to up to 5 years

DRUG

Cytarabine

1000 mg/m2/ on days 1, 3 and 5 of consolidation with 2h infusion

DRUG

Mercaptopurine

50 mg/m2 on days 1 to 28 of maintenance

DRUG

Methotrexate

1000 mg/m2 on day 1 of consolidation with 24h infusion; and 20 mg/m2 on days 1, 8, 15 and 22 of maintenance

DRUG

Ponatinib

15 mg per day from consolidation start up to 5 years

PROCEDURE

allogeneic stem cell transplantation

Allogeneic stem cell transplantation from hematpoietic stem cells progenitors of familiar or not familiar origin. Cord blood transplantation can also be done.

PROCEDURE

Total body irradiation

Fractionated dose with total dose of 12 Gy between days -4 and -1 of allogeneic stem cell transplantation (alloSCT)

DRUG

Cyclophosphamide

60 mg/kg on days -6 and -5 before alloSCT

DRUG

Fludarabine

30 mg/m2 intravenous on days -7, -6, -5 y -4 before alloSCT (alternative to cyclophosphamide)

Sponsors & Collaborators

• PETHEMA Foundation

  lead OTHER

Principal Investigators

• Josep M Ribera Santasusana, MD · Institut Catala d'Oncologia-Hospital Universitari Germans Trias i Pujol

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-12-25

Primary Completion

2028-12-25

Completion

2030-12-25