Study in Adult Ph-positive ALL

NCT04688983 | Unknown Phase 2 DMC

• 1 other identifier: SPON-1751-19
• Study Type: interventional
• Target: 180
• Locations: 0 countries
• Sites: N/A

Brief Summary

An Open Label, 3-arm, Randomised Phase II Study to Compare the Safety and Efficacy of Ponatinib in Combination With Either Chemotherapy or Blinatumomab With Imatinib Plus Chemotherapy as Front-line Therapy for Patients Aged 55 Years and Over With Philadelphia Chromosome Positive (Ph+ or BCR-ABL+) Acute Lymphoblastic Leukemia (ALL)

Conditions

Acute Lymphoblastic Leukemia, Adult

Outcome Measures

Primary Outcomes (1)

• Number of patients with a demonstrable molecular response

  Achievement of a molecular response in treatment arms 1 and 2 defined by a BCR-ABL1/ABL1 (B/A) transcript ratio of ≤10-4 by the time point scheduled for MRD analysis

  Within 5 months after start of study treatment

Study Arms (3)

Arm 1

ACTIVE COMPARATOR

Ponatinib plus standard induction and consolidation

Drug: Ponatinib

Arm 2

ACTIVE COMPARATOR

Imatinib plus standard induction and consolidation (comparator arm)

Drug: Imatinib

Arm 3

EXPERIMENTAL

Ponatinib plus Blinatumomab

Drug: Ponatinib; Drug: Blinatumomab

Interventions

Ponatinib DRUG

30 mg QD starting day 1, given continuously unless interruption required for toxicity

Arm 1; Arm 3

Blinatumomab DRUG

A single cycle of blinatumomab treatment is 6 weeks in duration, which includes 4 weeks of blinatumomab CIVI followed by a 2-week treatment-free interval.

Also known as: Blincyto

Arm 3

Imatinib DRUG

starting day 1, given orally at 400mg BID continuously for 8 weeks

Arm 2

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients \> 55 years (biological age)
• Philadelphia chromosome or BCR-ABL positive acute lymphoblastic leukaemia
• Not previously treated except with corticosteroids, single dose vincristine or up to three doses of cyclophosphamide (maximum cumulative dose 1g/m2) or intrathecal therapy to control meningeal leukaemia
• No uncontrolled CNS involvement
• WHO performance status \<2
• Normal serum levels \> LLN (lower limit of normal) of potassium and magnesium, or corrected to within normal limits with supplements, prior to the first dose of study medication
• Signed written inform consent
• Molecular evaluation for BCR-ABL1 performed
• Willingness of sexually active male subjects whose sexual partners are women of childbearing potential (WOCBP), to use an effective form of contraception (pearl index \< 1%) during the study and at least 6 months thereafter. Effective forms of contraception are complete sexual abstinence (refraining from heterosexual intercourse during the entire period of risk associated with the study treatments), combined oral contraceptive, hormone IUCD, vaginal hormone ring, transdermal contraceptive patch, contraceptive implant or depot contraceptive injection in combination with a second method of contraception like a condom or a cervical cap / diaphragm with spermicide or surgical sterilisation (vasectomy) in male patients.
• Women of non-childbearing potential defined as sexually mature women who have undergone a hysterectomy or surgical sterilization or who have been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months).

You may not qualify if:

• Patient previously treated with tyrosine kinase inhibitors
• Known impaired cardiac function, including any of the following:
• LVEF \< 40%
• Complete left bundle branch block
• Right bundle branch block plus left anterior hemiblock, bifascicular block
• History of or presence of clinically significant ventricular or atrial tachyarrhythmias
• Clinically significant resting bradycardia (\< 50 beats per minute)
• Congenital long QT syndrome or QTcF \>470 msec on screening ECG. If QTc \> 470 msec and electrolytes are not within normal ranges before ponatinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion.
• Myocardial infarction within 12 months prior to starting study treatment
• Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)
• Symptomatic peripheral vascular disease
• Any history of ischemic stroke or transient ischemic attacks (TIAs)
• Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
• History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis (with exception of CNS leukemia that is well controlled with intrathecal therapy)
• Active ALL in the CNS (confirmed by CSF analysis) or testes (by clinical assessment).

Sponsors & Collaborators

• Cardiff University: lead

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

ponatinib; blinatumomab; Imatinib Mesylate

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)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Central Study Contacts

Oliver Ottmann

CONTACT

02920742375; ottmanno@cardiff.ac.uk

Ian Thomas

CONTACT

thomasif@cardiff.ac.uk

Study Design

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

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: December 30, 2020
• Study Start: January 1, 2021
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2026
• Last Updated: December 30, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share