Ponatinib Plus Chemotherapy in Acute Lymphoblastic Leukemia Patients

NCT05306301 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: ALL2922
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 24

Brief Summary

Acute lymphoblastic leukemia (ALL) is the most frequent cancer in children, decreases in adolescence and adulthood, and a second peak can be recorded starting from the 6th decade of life. While the outcome in children is excellent, in the adolescent/adult population, the prognosis, though improved over the decades, it is still unsatisfactory and novel biologically-driven approaches are urgently needed. In this setting, thanks to the introduction of genome wide technologies, it was possible to recognize specific subset of ALL. Among those, the BCR/ABL1-like ALL are of extreme importance, since they are characterized by an unfavourable outcome and, on the other hand, can benefit of a targeted treatment, in particular with the pan-tyrosine kinase inhibitor ponatinib. The primary objective is to evaluate the clinical response - in terms of MRD negativity - in patients with a BCR/ABL1-like profile, according to the BCR/ABL1-like predictor tool, treated with Ponatinib in combination with chemotherapy.

Conditions

Chemotherapy; Leukemia, Acute Lymphoblastic

Outcome Measures

Primary Outcomes (1)

• MRD Negativity Rate after 3 cycles (TP2) in patients with BCR/ABL1-like ALL treated with a Ponatinib plus chemotherapy approach

  The primary outcome is to evaluate the clinical response - in terms of MRD negativity - in patients with a BCR/ABL1-like profile, according to the BCR/ABL1-like predictor tool, treated with Ponatinib in combination with chemotherapy

  3 months

Study Arms (1)

Patients With BCR/ABL1-Like Acute Lymphoblastic Leukemia

EXPERIMENTAL

In the run-in phase, patients will receive a dosage of 15 mg of ICLUSIG (ponatinib). If there are no toxicities observed, 30 mg of ponatinib will be administered in the remaining patients. MRD of patients will be evaluated on weeks 4, 10, 16, and 22. If a donor is available, MRD-positive patients will proceed to an allogeneic transplant after cycle 3. If there is no donor available, they'll continue treatment with 5 additional consolidation/reinduction blocks, followed by 24 28-day cycles of maintenance. Induction/consolidation cycles are administered at 28 (cycles 1-2) and 21(cycles 2-8) day intervals.

Drug: Ponatinib

Interventions

Ponatinib DRUG

Ponatinib is a novel, synthetic, orally-active TKI discovered using a computational and structure based drug design approach. Ponatinib was specifically designed to inhibit all clinically relevant variants of BCR-ABL1, including the T315I mutant (15-17). In vitro assays have demonstrated that Ponatinib potently inhibits the kinase enzymatic activity of the T315I ABL kinase domain, as well as that of the native (unmutated) enzyme. In leukemia cell lines expressing these BCR-ABL1 variants, Ponatinib potently inhibited BCR-ABL1 signaling, leading to the reduction of cellular proliferation and induction of apoptosis. Ponatinib also inhibits the proliferation of cell lines expressing other major clinically-observed Imatinib-resistant mutants of BCR-ABL1.

Patients With BCR/ABL1-Like Acute Lymphoblastic Leukemia

Eligibility Criteria

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

You may qualify if:

• Age 18-65 years.
• De novo Ph+-like ALL, as defined by the BCR/ABL1-like predictor (13).
• WHO score ≤2.
• Adequate liver function, as defined by the following criteria: total serum bilirubin ≤1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, alanine aminotransferase (ALT) ≤2.5 × ULN or ≤2.5 x ULN or leukemia related.
• Adequate pancreatic function as defined by serum lipase and amylase ≤1.5 × ULN or leukemia related.
• No history of dyslipidemia, thrombotic events or cardiac disease.
• For females of childbearing potential, a negative pregnancy test must be documented.
• Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from enrollment through 12 months after the end of treatment.
• Signed informed consent, according to ICH/EU/GCP and national regulation.

You may not qualify if:

• WHO performance status \>2.
• Active HBV or HCV hepatitis, or AST/ALT \> 2.5 x ULN and bilirubin \> 1.5 x ULN.
• History of acute pancreatitis within 1 year of study or history of chronic pancreatitis.
• History of alcohol abuse.
• Ongoing or active infections.
• Uncontrolled hypertriglyceridemia (triglycerides \>450 mg/dL).
• Clinically significant, uncontrolled or active cardiovascular disease, specifically including, but not restricted to:
• Any history of myocardial infarction, stroke, or revascularization, unstable angina or transient ischemic attack within 6 months prior to enrollment,
• Congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards,
• History of clinically significant (as determined by the treating physician) atrial arrhythmia,
• Any history of ventricular arrhythmia,
• Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism.
• Uncontrolled hypertension (diastolic blood pressure \>90 mm Hg; systolic \>140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control.
• Taking medications that are known to be associated with torsades de pointes.
• Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib.

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (24)

Ematologia con Unità di Trapianto

Avellino, AV, 83100, Italy

Location

Ematologia Presidio Ospedaliero Tortora

Pagani, SA, Italy

Location

Ematologia ASST Papa Giovanni XXIII

Bergamo, Italy

Location

Ematologia AOU S.ORSOLA-MALPIGHI

Bologna, Italy

Location

Ematologia ASST Spedali Civili

Brescia, Italy

Location

Ematologia AOU Policlinico Vittorio Emanuele-Ferrarotto

Catania, Italy

Location

Ematologia AOU Careggi

Florence, Italy

Location

Ematologia Ospedale V.Fazzi

Lecce, Italy

Location

Ematologia Ospedale dell'Angelo

Mestre, Italy

Location

Ematologia Ospedale Maggiore Policlinico

Milan, Italy

Location

Ematologia AOU Federico II

Naples, Italy

Location

Ematologia AOU Maggiore della Carità

Novara, Italy

Location

Ematologia AO Ospedali Riuniti Villa Sofia Cervello

Palermo, Italy

Location

Ematologia Fondazione Policlinico San Matteo

Pavia, Italy

Location

Ematologia Presidio Ospedaliero Spirito Santo

Pescara, Italy

Location

Ematologi Presidio Ospedaliero Guglielmo da Saliceto

Piacenza, Italy

Location

Ematologia Presidio Ospedaliero Infermi

Rimini, Italy

Location

Dipartimento di Medicina Traslazionale e di Precisione - Ematologia

Roma, Italy

Location

Ematologia AOU Policlinico Tor Vergata

Roma, Italy

Location

Ematologia Policlinico A.Gemelli

Roma, Italy

Location

Ematologia AOU Senese

Siena, Italy

Location

Ematologia Ospedale Mauriziano

Torino, Italy

Location

Ematologia Ospedale S.Giovanni Battista Molinette

Torino, Italy

Location

Ematologia Policlinico G.B. Rossi

Verona, Italy

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

ponatinib

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

Study Officials

• Sabina Chiaretti

  Ematologia - Policlinico Umberto I di Roma

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2022
• First Posted: April 1, 2022
• Study Start: October 5, 2022
• Primary Completion: March 1, 2026
• Study Completion (Estimated): July 1, 2028
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

IT (24)