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Treatment Protocol for Newky Diagnosed Adult Ph Positive ALL

ConditionsLymphoblastic LeukemiaPhiladelphia-Positive ALLAdult ALL
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorPETHEMA Foundation

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients with de novo avute lymphoblastic leukeima (ALL) Philadelphia chromosome-positive (BCR::ABL1) aged ≥18 years.

CML blast crisis will be included. These patients will always receive transplantation, regardless of the molecular response or the genetic risk, following the recommendations of the SEHH CML group (Chronic Myleoid Leukemia Group from the Spanish Society of Hematology).

Performance status 0-2; patients with performance status>2 attributable to ALL can be included.

Patients without functional alteration of organs; liver function: total bilirubin, GOT, GPT, GGT and alkaline phosphatase less than 3 times the upper limit of the normal range of the laboratory; renal function: serum creatinine <2 mg/dl or creatinine clearance > 30 ml/min (except altered renal function attributable to ALL); normal heart function: EF ventricular > 50%; absence of severe chronic respiratory disease. In case that the alterations are secondary to the disease, it is at the discretion of the physician to determine if the patient can be included in the study.

Disqualifiers

Any other subtype of ALL.

Patients with chronic liver disease.

Patients with chronic respiratory failure.

Renal failure not due to ALL.

Trial population

Adults aged 18 or over years with newly diagnosed Ph-positive or BCR::ABL1-positive acute lymphoblastic leukemia (Ph+ ALL).

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • Vincristine

    Drug

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

  • Dexamethasone

    Drug

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

  • Imatinib

    Drug

    600 mg per day from 1 to up to 5 years

  • Cytarabine

    Drug

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

  • Mercaptopurine

    Drug

    50 mg/m2 on days 1 to 28 of maintenance

  • Methotrexate

    Drug

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

  • Ponatinib

    Drug

    15 mg per day from consolidation start up to 5 years

  • allogeneic stem cell transplantation

    Procedure/Surgery

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

  • Total body irradiation

    Procedure/Surgery

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

  • Cyclophosphamide

    Drug

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

  • Fludarabine

    Drug

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

Treatment groups

150 Participants
are divided into 2 treatment groups
Group A: Complete molecular response and low risk genetics6 interventions
Group B: Not complete molecular response or high-risk genetics (IKZF1plus)11 interventions

Trial outcomes

Primary outcomes

1

Overall survival

Improvement of OS compared to that observed in the previous protocols (PETHEMA LALPh08 and LALOPh07).

Time frame
5 Years

Secondary outcomes

1

Change the complete molecular response (CMR) rate with Ponatinib

Change the CMR rate at the end of consolidation with the administration of ponatinib to those patients who do not achieve CMR at the end of induction or have high-risk genetics (IKZF1plus).

Time frame
5 Years
2

Limit the number of alloTPH compared to that observed in the previous protocols (PETHEMA LALPh08 and LALOPh07).

Limit the number of alloTPH to any of the following: * Lack of CMR at the end of consolidation. * High-risk genetics (IKZF1plus).

Time frame
5 Years
3

Maintenance

To assess the number of non-transplanted participants who receive maintenance treatment.

Time frame
5 Years
4

Treatment with TKI after HSCT

To assess the number of transplanted patients who receive TKI maintenance treatment preemptively (upon of MRD\>0.01%).

Time frame
5 Years

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

PETHEMA Foundation

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: