Overview

Combination Chemotherapy and Ponatinib Hydrochloride in Treating Patients With Acute Lymphoblastic Leukemia

Status:
Recruiting
Trial end date:
2021-10-31
Target enrollment:
0
Participant gender:
All
Summary
This phase II trial studies the side effects and how well combination chemotherapy and ponatinib hydrochloride work in treating patients with acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone, 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. Ponatinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy and ponatinib hydrochloride may be an effective treatment for acute lymphoblastic leukemia.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
M.D. Anderson Cancer Center
Collaborator:
Ariad Pharmaceuticals
Treatments:
Antibodies
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
BB 1101
Cortisone
Cyclophosphamide
Cytarabine
Daunorubicin
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Doxorubicin
Immunoglobulins
Lenograstim
Leucovorin
Levoleucovorin
Liposomal doxorubicin
Mesna
Methotrexate
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Ponatinib
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Prednisone
Rituximab
Vincristine
Criteria
Inclusion Criteria:

- Diagnosis of one of the following:

- Previously untreated Ph-positive ALL (either t[9;22] and/or bcr-abl positive)
(includes patients initiated on first course of hyper-CVAD before cytogenetics
known) or with lymphoid accelerated or blast phase chronic myelogenous leukemia
(CML)

- Previously treated Ph-positive ALL or CML (in accelerated phase or blast phase),
after 1-2 courses of chemotherapy with or without other tyrosine kinase
inhibitors (TKIs)

- If they achieved complete response (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

- Performance status =< 2 (Eastern Cooperative Oncology Group [ECOG] scale)

- Total serum bilirubin =< 1.5 x upper limit of normal (ULN), unless due to Gilbert's
syndrome

- Alanine aminotransferase (ALT) =< 2 x ULN

- Aspartate aminotransferase (AST) =< 2.5 x ULN

- Serum lipase and amylase =< 1.5 x ULN

- For females of childbearing potential, a negative pregnancy test must be documented
prior to randomization

- Female and male patients who are fertile must agree to use an effective form of
contraception with their sexual partners from randomization through 4 months after the
end of treatment

- Adequate cardiac function as assessed clinically by history and physical examination

- Signed informed consent

Exclusion Criteria:

- 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 (triglycerides > 450 mg/dL)

- 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

- Clinically significant, uncontrolled, or active cardiovascular disease, specifically
including, but not restricted to:

- Any history of myocardial infarction (MI), stroke, or revascularization

- Unstable angina or transient ischemic attack prior to enrollment

- 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

- Any history of clinically significant atrial or ventricular arrhythmias (such as
atrial fibrillation, ventricular tachycardia, ventricular fibrillation, or
torsades de pointes) as determined by the treating physician

- Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 470 msec)
unless corrected after electrolyte replacement

- Any history of venous thromboembolism including deep venous thrombosis or
pulmonary embolism

- Uncontrolled hypertension (diastolic blood pressure > 90 mmHg; systolic > 140
mmHg); patients with hypertension should be under treatment on study entry to
effect blood pressure control

- Patients currently taking drugs that are generally accepted to have a risk of causing
torsades de pointes (unless these can be changed to acceptable alternatives)

- Taking any medications or herbal supplements that are known to be strong inhibitors of
cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) within at least 14 days
before the first dose of ponatinib

- Prior history of treatment with ponatinibfor > 1 month; patient who has been treated
with ponatinib for 1 month prior starting the treatment is eligible

- 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; patient who has been treated with ponatinib for 1 month prior starting
the treatment is eligible

- 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)

- 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