Treatment Protocol for Newky Diagnosed Adult Ph Positive ALL

NCT06175702 | Not Yet Recruiting

• 1 other identifier: PETHEMA LALPh2022
• Study Type: observational
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief 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

Keywords

Acute Lymphoblastic Leukemia; Philadelphia (BCR::ABL1) positive; Adults

Outcome Measures

Primary Outcomes (1)

• Overall survival

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

  5 Years

Secondary Outcomes (5)

• Change the complete molecular response (CMR) rate with Ponatinib

  5 Years

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

  5 Years

• Maintenance

  5 Years

• Treatment with TKI after HSCT

  5 Years

• Assess the frequency and degree of Adverse Events

  5 Years

Study Arms (2)

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; Drug: Dexamethasone; Drug: Imatinib; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Methotrexate

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; Drug: Dexamethasone; Drug: Imatinib; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Ponatinib; Procedure: allogeneic stem cell transplantation; Procedure: Total body irradiation; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Vincristine DRUG

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

Complete molecular response and low risk genetics; Not complete molecular response or high-risk genetics (IKZF1plus)

Dexamethasone DRUG

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

Complete molecular response and low risk genetics; Not complete molecular response or high-risk genetics (IKZF1plus)

Imatinib DRUG

600 mg per day from 1 to up to 5 years

Complete molecular response and low risk genetics; Not complete molecular response or high-risk genetics (IKZF1plus)

Cytarabine DRUG

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

Complete molecular response and low risk genetics; Not complete molecular response or high-risk genetics (IKZF1plus)

Mercaptopurine DRUG

50 mg/m2 on days 1 to 28 of maintenance

Complete molecular response and low risk genetics; Not complete molecular response or high-risk genetics (IKZF1plus)

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

Complete molecular response and low risk genetics; Not complete molecular response or high-risk genetics (IKZF1plus)

Ponatinib DRUG

15 mg per day from consolidation start up to 5 years

Not complete molecular response or high-risk genetics (IKZF1plus)

allogeneic stem cell transplantation PROCEDURE

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

Not complete molecular response or high-risk genetics (IKZF1plus)

Total body irradiation PROCEDURE

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

Not complete molecular response or high-risk genetics (IKZF1plus)

Cyclophosphamide DRUG

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

Not complete molecular response or high-risk genetics (IKZF1plus)

Fludarabine DRUG

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

Not complete molecular response or high-risk genetics (IKZF1plus)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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).

You may qualify if:

• 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.

You may not qualify if:

• Any other subtype of ALL.
• Patients with chronic liver disease.
• Patients with chronic respiratory failure.
• Renal failure not due to ALL.
• Lipase and amylase\>1.5× ULN.
• Patients with positive HIV serology.
• Serious neurological alterations not due to ALL.
• Serious general condition condition (grades 3 or 4 on the WHO scale) not attributable to ALL.
• Pregnant or breastfeeding women.
• 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.

Sponsors & Collaborators

• PETHEMA Foundation: lead

Related Publications (33)

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Related Links

• Web page of the sponsor of the study

Biospecimen

Retention: SAMPLES WITH DNA

Blood Samples

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Vincristine; Dexamethasone; Imatinib Mesylate; Cytarabine; Mercaptopurine; Methotrexate; ponatinib; Whole-Body Irradiation; Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Pyrimidines; Cytidine; Pyrimidine Nucleosides; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Sulfur Compounds; Purines; Aminopterin; Pterins; Pteridines; Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Josep M Ribera Santasusana, MD

  Institut Catala d'Oncologia-Hospital Universitari Germans Trias i Pujol

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Josep M Ribera Santasusana, MD

CONTACT

0034934978387; jribera@iconcologia.net

Anna Torrent, MD

CONTACT

0034934978987; atorrent@iconcologia.net

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2023
• First Posted: December 19, 2023
• Study Start: December 25, 2023
• Primary Completion (Estimated): December 25, 2028
• Study Completion (Estimated): December 25, 2030
• Last Updated: December 19, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share