Combining blinatumomab and asciminib for treating a type of leukemia

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

This study is testing if combining two drugs, blinatumomab and asciminib, can help people with a specific type of leukemia feel better and improve their chances of recovery.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, blinatumomab, asciminib
• Locations: 2 sites (The Bronx, New York and 1 other locations)
• Trial ID: NCT06308588 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of combining blinatumomab and asciminib in patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL). The study will assess the minimum safe dose of asciminib and measure the rate of measurable residual disease negativity using advanced genetic testing. Additionally, it will explore various clinical outcomes such as complete molecular response, overall survival, and the safety profile of the treatment combination. The trial includes both newly diagnosed and relapsed/refractory cases of Ph+ ALL.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with newly diagnosed or relapsed/refractory Ph-positive ALL who are not suitable for intensive chemotherapy.

Not a fit: Patients with other types of leukemia or those who have not been diagnosed with Ph-positive ALL may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could significantly improve disease control and survival rates for patients with Ph+ ALL.

How similar studies have performed: Other studies have shown promising results with similar treatment combinations in hematological malignancies, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Diagnosis of one of the following:

   a) Participants ≥18 years of age with previously untreated or minimally pretreated Ph-positive ALL who are not suitable candidates for intensive chemotherapy. Participants who have received no more than one or two courses of chemotherapy with or without other TKIs are considered minimally pretreated and still eligible if they have persistently detectable MRD.

   i. If they are in morphologic remission at enrollment, they are evaluable only MRD responses, RFS and OS b) Participants ≥ 12 years of age with relapsed/refractory Ph-positive ALL or with previously treated lymphoid blast phase CML
2. Performance status ≤2 (ECOG Scale) if age ≥18 years or Lansky ≥50 if age \<18 years
3. Weight ≥40kg
4. 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
5. Adequate renal function defined as:

   a) Creatinine clearance ≥30 mL/min
6. Adequate pancreatic function as defined by the following criteria:

   a) Serum lipase and amylase \< 1.5 x ULN
7. Adequate cardiac function as assessed clinically by history and physical examination.
8. For females of childbearing potential, a negative urine pregnancy test must be documented
9. 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
10. Ability to understand and the willingness to sign a written informed consent document.
11. 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 patient has rapidly progressive disease judged to be life-threatening by the investigator. Cytarabine 2 g/m2 (or alternative) for cytoreduction is permitted.
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.

Where this trial is running

The Bronx, New York and 1 other locations

• Montefiore Einstein Comprehensive Cancer Center — The Bronx, New York, United States (Not_yet_recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Nicholas Short, MD — M.D. Anderson Cancer Center
• Study coordinator: Nicholas Short, MD

Conditions Philadelphia Chromosome-Positive; Acute Lymphoblastic Leukemia