Low-Intensity Chemotherapy, Ponatinib and Blinatumomab in Treating Patients With Philadelphia Chromosome-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia
Phase II Study of the Sequential Combination of Low-Intensity Chemotherapy and Ponatinib Followed by Blinatumomab and Ponatinib in Patients With Philadelphia Chromosome (Ph)-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL)
2 other identifiers
interventional
22
1 country
1
Brief Summary
This phase II trial studies how well low-intensity chemotherapy and ponatinib work in treating patients with Philadelphia chromosome-positive and/or BCR-ABL positive acute lymphoblastic leukemia that may have come back or is not responding to treatment. Drugs used in chemotherapy, such as cyclophosphamide, vincristine, dexamethasone, methotrexate, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with rituximab and blinatumomab, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Granulocyte colony stimulating factor helps the bone marrow make recover after treatment. Giving low-intensity chemotherapy, ponatinib, and blinatumomab may work better in treating patients with acute lymphoblastic leukemia.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Feb 2018
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 5, 2017
CompletedFirst Posted
Study publicly available on registry
May 10, 2017
CompletedStudy Start
First participant enrolled
February 8, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 28, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 28, 2027
February 17, 2026
February 1, 2026
9.1 years
May 5, 2017
February 12, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Complete molecular response (CMR) in newly diagnosed Philadelphia chromosome (Ph)-positive and/or BCR-ABL-positive participants
The CMR rate within the first 3 courses for cohort 1 or rate within the first 2 courses for cohort 2 will be estimated along with the 95% credible intervals. Similar analyses will be performed for estimating the rate of complete cytogenetic response and major molecular response rates.
Up to 84 days (3 courses)
Overall response (OR) in participants with relapsed/refractory acute lymphoblastic leukemia
Overall response is defined as complete response (CR) + complete response with hematologic improvement (CRi) in participants with relapsed/refractory disease.
Up to 6 years
Secondary Outcomes (5)
Complete cytogenetic response
Up to 6 years
CMR for relapsed/refractory population
Up to 6 years
Event-free survival (EFS)
From the first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 6 years
Overall survival (OS)
From the first day of treatment to time of death from any cause, assessed up to 6 years
Incidence of adverse events (AEs)
Up to 6 years
Study Arms (1)
Treatment (chemotherapy, ponatinib, blinatumomab)
EXPERIMENTALSee Detailed Description.
Interventions
Given via central catheter
Given IV
Given intrathecally or IV
Given SC
Given intrathecally or IV
Given SC
Given PO
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Patients \>= 18 years of age with previously untreated Ph-positive ALL (either t(9;22) and/or BCR-ABL positive) (includes patients initiated on first cycle of hyper-CVAD before cytogenetics known. These patients could have received one or two cycles of chemotherapy with or without other TKIs and still eligible.
- If they achieved CR, they are assessable only for event-free and overall survival, or
- If they failed to achieve CR, they are assessable for CR, event-free, and overall survival.
- Patients \>= 18 years of age with relapsed/refractory Ph-positive ALL or lymphoid accelerated or blast phase chronic myelogenous leukemia (CML)
- Performance status =\< 2 (Eastern Cooperative Oncology Group \[ECOG\] scale)
- Total serum bilirubin =\< 2 x upper limit of normal (ULN), unless due to Gilbert's syndrome
- Alanine aminotransferase (ALT) =\< 3 x ULN
- Aspartate aminotransferase (AST) =\< 3 x ULN
- Serum lipase and amylase =\< 1.5 x ULN
- Creatinine =\< 2.0 mg/dl
- Female patients who: are postmenopausal for at least 1 year before the screening visit, OR are surgically sterile, OR if they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
- Male patients, even if surgically sterilized (i.e., status post-vasectomy), who: agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
- Adequate cardiac function as assessed clinically by history and physical examination
- Signed informed consent
You may not qualify if:
- Active serious infection not controlled by oral or intravenous antibiotics
- Known active hepatitis B. Patients with chronic hepatitis B who are on appropriate viral suppressive therapy may be allowed after discussion with the principal investigator (PI)
- History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
- History of alcohol abuse
- Uncontrolled hypertriglyceridemia
- 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
- Active grade III-V cardiac failure as defined by the New York Heart Association criteria
- Uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: myocardial infarction (MI), stroke, or revascularization within 3 months; unstable angina or transient ischemic attack; congestive heart failure prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards prior to enrollment; diagnosed or suspected congenital long QT syndrome; clinically significant atrial or ventricular arrhythmias as determined by the treating physician; prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (\> 470 msec) unless corrected after electrolyte replacement. or approved by cardiologist; Significant venous or arterial thromboembolism including deep venous thrombosis or pulmonary embolism. Patients with a history of treated prior superficial or catheter associated phlebitis will not be considered as significant embolism and after discussion with principal investigator (PI) will not be excluded from eligibility. Uncontrolled hypertension (diastolic blood pressure \> 90 mmHg; systolic \> 140mmHg). Patients with hypertension should be under treatment on study entry to effect blood pressure control
- Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days or 5 half-lives before the first dose of ponatinib in patients with newly diagnosed only
- History or presence of clinically relevant central nervous system (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. Patients with active CNS leukemia will NOT be excluded
- Current autoimmune disease or history of autoimmune disease with potential CNS involvement
- 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
- 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
- History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., von Willebrand's disease); and diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
- Patients with documented significant pleural or pericardial effusions unless they are thought to be secondary to their leukemia
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Elias Jabbour
M.D. Anderson Cancer Center
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
May 5, 2017
First Posted
May 10, 2017
Study Start
February 8, 2018
Primary Completion (Estimated)
February 28, 2027
Study Completion (Estimated)
February 28, 2027
Last Updated
February 17, 2026
Record last verified: 2026-02