Phase II Study of the Combination of Blinatumomab and Asciminib in Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Phase II Study of the Combination of Blinatumomab and Asciminib in Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06308588
• Other study ID #: 2024-0054
• Secondary ID: NCI-2024-02121
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 30, 2024
• Est. completion date: May 2029

Study information

• Verified date: April 2024
• Source: M.D. Anderson Cancer Center
• Contact: Nicholas Short, MD
• Phone: (713) 563-4485
• Email: nshort[@]mdanderson.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To learn if the combination of blinatumomab and asciminib can help to control Ph+ ALL.

Description:

Primary Objectives

• To evaluate the rate of next-generation sequencing (NGS) measurable residual disease (MRD) negativity in cohort 1 (newly diagnosed Ph-positive ALL) and the overall response (CR+CRi) rate in cohort 2 (relapsed/refractory disease).

Secondary Objectives

• To evaluate other clinical efficacy endpoints (complete molecular response [CMR] rate, CR rate, relapse-free survival and overall survival)

• To determine the safety of the combination regimen

Exploratory Objectives

• To characterize the role of ABL1 kinase domain mutations on treatment failure and relapse

• To assess concordance/discordance between MRD assessed by PCR for BCR::ABL1 and next-generation sequencing MRD

• To determine the effect of the combination regimen on immune cell subsets

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: May 2029
• Est. primary completion date: May 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Diagnosis of one of the following:

1. Participants = 18 years of age with previously untreated Ph-positive ALL. These patients could have received one or two courses of chemotherapy with or without other TKIs and still eligible. i. If they are in morphologic remission at enrollment, they are evaluable only MRD responses, RFS and OS, or ii. If they have active disease at enrollment, they are evaluable for all response and survival endpoints

2. Participants = 18 years of age with relapsed/refractory Ph-positive ALL or with previously treated lymphoid blast phase CML

2. Performance status =2 (ECOG Scale)

3. Adequate liver function as defined by the following criteria (unless the increased values are judged to be leukemia disease related):

1. Total serum bilirubin = 2 x upper limit of normal (ULN), unless due to Gilbert's syndrome

2. Alanine aminotransferase (ALT) = 3 x ULN, OR

3. Aspartate aminotransferase (AST) = 3 x ULN

4. Adequate pancreatic function as defined by the following criteria:

a) Serum lipase and amylase < 1.5 x ULN

5. Adequate cardiac function as assessed clinically by history and physical examination.

6. For females of childbearing potential, a negative urine pregnancy test must be documented

7. Willingness to use adequate contraception prior to study entry, for the duration of study participation, and for 4 months after completion of study participation. For women of child-bearing potential, adequate methods of contraception include: complete abstinence, hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device (IUD), tubal Ligation or hysterectomy, subject/partner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide

8. Ability to understand and the willingness to sign a written informed consent document.

9. Signed informed consent

Exclusion Criteria:

1. Active serious infection not controlled by oral or intravenous antibiotics.

2. Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma) that in the investigator's opinion will shorten survival to less than 1 year.

3. Active Grade III-V cardiac failure as defined by the New York Heart Association Criteria.

4. Prolonged QTc interval on pre-entry electrocardiogram (> 470 msec) unless corrected after electrolyte replacement or approved by cardiologist

5. 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, or psychosis. (Participants with active CNS leukemia will NOT be excluded)

6. Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or participants has rapidly progressive disease judged to be life-threatening by the investigator.

7. Pregnant and lactating women will not be eligible; women of childbearing potential should have a negative pregnancy test prior to entering on the study and be willing to practice methods of contraception. Women do not have childbearing potential if they have had a hysterectomy or are postmenopausal without menses for 12 months. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Philadelphia Chromosome
• Philadelphia Chromosome-Positive
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Blinatumomab
Given by Infusion
• Asciminib
Given by PO

Locations

Country	Name	City	State
United States	MD Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and adverse events (AEs)	Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0	Through study completion; an average of 1 year.

External Links

•   MD Anderson Cancer Center