Treatment Protocol for Newky Diagnosed Adult Ph Positive ALL (LALPh2022)

December 15, 2023 updated by: PETHEMA Foundation

Treatment Protocol for Newky Diagnosed Adult Ph-Chromosome Positive (BCR::ABL1) Acute Lymphoblastic Leukemia (LALPh2022)

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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 each 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 induction phase with vincristine (dose 1.5 mg/m2 at days 1, 8, 15 and 22), dexamethasone (dose 40 mg days 1-2, 8-9,15-16 and 22-23) will be given together with the TKI imatinib (dose 600 mg from day to consolidation start) to all patients of all ages as induction to remission phase.

Consolidation treatment will continue with low-dose chemotherapy with methotrexate (dose 1000 mg/m2 on day 1 with 24h infusion) and arabinoside of cytarabine (dose 1000 mg/m2/ days 1, 3 and 5 with 2h infusion) with imatinib (dose 600 mg per day) if the patient fullfills both criteria: i) to show a measurable residual disease (MRD) value <0,01% at 3 month of therapy, and ii) not showing IKZF1plus genetics.

Those patients having any of these 2 conditions will be considered high-risk patients and will recieve consolidation treatment intensification with low-dose chemotherapy (same as described above) plus ponatinib (dose 30 mg per day) as TKI and allogeneic stem cell transplantation (alloSCT) followed by maintenance chemotherapy with mercaptopurine (dose 50 mg/m2 on days 1 to 28) and methotrexate (dose 20 mg/m2 on days 1, 8, 15 and 22) together with imatinib (dose 600 mg per day) or ponatinib (15 mg per day) up to 5 years. The remaining patients (standard-risk) will receive maintenance chemotherapy (as described above) together with imatinib (dose 600 mg per day) or ponatinib (15 mg per day) up to 5 years and will not be submitted to alloSCT.

Study Type

Observational

Enrollment (Estimated)

150

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

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

Description

Inclusion Criteria:

  1. Patients with de novo avute lymphoblastic leukeima (ALL) Philadelphia chromosome-positive (BCR::ABL1) aged ≥18 years.
  2. 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).
  3. Performance status 0-2; patients with performance status>2 attributable to ALL can be included.
  4. 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.

Exclusion Criteria:

  1. Any other subtype of ALL.
  2. Patients with chronic liver disease.
  3. Patients with chronic respiratory failure.
  4. Renal failure not due to ALL.
  5. Lipase and amylase>1.5× ULN.
  6. Patients with positive HIV serology.
  7. Serious neurological alterations not due to ALL.
  8. Serious general condition condition (grades 3 or 4 on the WHO scale) not attributable to ALL.
  9. Pregnant or breastfeeding women.
  10. Impaired cardiac function (defined by an ejection fraction less than 50%), any clinically significant active or uncontrolled cardiovascular condition, uncontrolled hypertension, arrhythmias, ischemic cardiovascular or neurological events, deep vein thrombosis, pulmonary thromboembolism, history of acute pancreatitis in the year before diagnosis of ALL or history of chronic pancreatitis and triglycerides >450 mg/dL.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Complete molecular response and low risk genetics
Patients in Complete Remission and Complete Molecular Response at end Induction therapy will receive consolidation with imatinib (or dasatinib if intolerance) and chemotherapy, unless they show the IKZF1plus genotype, which will imply switch to the not complete molecular response or high-risk genetics (IKZ1plus) group.
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
Not complete molecular response or high-risk genetics (IKZF1plus)
Patients in Complete Remission and without Complete Molecular Response at the end of Induction therapy or showing the IKZF1plus genotype, will receive consolidation treatment with ponatinib and chemotherapy followed by allogeneic stem cell transplantation and maintenance therapy.
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 5 Years
Improvement of OS compared to that observed in the previous protocols (PETHEMA LALPh08 and LALOPh07).
5 Years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change the complete molecular response (CMR) rate with Ponatinib
Time Frame: 5 Years
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).
5 Years
Limit the number of alloTPH compared to that observed in the previous protocols (PETHEMA LALPh08 and LALOPh07).
Time Frame: 5 Years

Limit the number of alloTPH to any of the following:

  • Lack of CMR at the end of consolidation.
  • High-risk genetics (IKZF1plus).
5 Years
Maintenance
Time Frame: 5 Years
To assess the number of non-transplanted participants who receive maintenance treatment.
5 Years
Treatment with TKI after HSCT
Time Frame: 5 Years
To assess the number of transplanted patients who receive TKI maintenance treatment preemptively (upon of MRD>0.01%).
5 Years
Assess the frequency and degree of Adverse Events
Time Frame: 5 Years
Assess the frequency of cytopenias and degree. Assess the frequency of infections and degree. Assess the frequency of vascuar events and degree. Assess the frequency of hepatic events and degree. Assess the frequency of pancreatic events and degree.
5 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PETHEMA Foundation

Investigators

  • Principal Investigator: Josep M Ribera Santasusana, MD, Institut Català D'Oncologia-Hospital Universitari Germans Trias I Pujol

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 25, 2023

Primary Completion (Estimated)

December 25, 2028

Study Completion (Estimated)

December 25, 2030

Study Registration Dates

First Submitted

November 17, 2023

First Submitted That Met QC Criteria

December 15, 2023

First Posted (Estimated)

December 19, 2023

Study Record Updates

Last Update Posted (Estimated)

December 19, 2023

Last Update Submitted That Met QC Criteria

December 15, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PETHEMA LALPh2022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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