Low-Intensity Chemotherapy and Venetoclax in Treating Patients With Relapsed or Refractory B- or T-Cell Acute Lymphoblastic Leukemia
- Conditions
- Recurrent B Acute Lymphoblastic LeukemiaRecurrent T Acute Lymphoblastic LeukemiaRefractory B Acute Lymphoblastic LeukemiaRefractory T Acute Lymphoblastic Leukemia
- Registration Number
- NCT03808610
- Lead Sponsor
- M.D. Anderson Cancer Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria:<br><br> 1. Diagnosis of one of the following<br><br> 1. Patients = 18 years of age with relapsed/refractory B- or T-cell ALL (for phase<br> II only)<br><br> 2. Patients = 60 years of age with previously untreated B- or T-cell ALL. Patients<br> <60 years of age may be enrolled if they are considered unfit for intensive<br> chemotherapy<br><br> 3. Patients = 60 years of age with previously treated B- or T-cell ALL who<br> received 1-2 courses of any frontline chemotherapy. Patients <60 years of age<br> may be enrolled if they are considered unfit for intensive chemotherapy<br><br> - If they achieved CR/CRi, they are assessable only for event-free and<br> overall survival<br><br> - If they failed to achieve CR/CRi, they are assessable for response,<br> event-free, and overall survival<br><br> 2. Performance status = 3 (Eastern Cooperative Oncology Group [ECOG] Scale)<br><br> 3. Adequate liver and renal function as defined by the following criteria:<br><br> - Total serum bilirubin = 1.5 x upper limit of normal (ULN)<br><br> - Alanine aminotransferase (ALT) = 3 x ULN, unless due to disease involvement of<br> the liver or hemolysis, in which case an ALT = 10 x ULN is acceptable<br><br> - Aspartate aminotransferase (AST) = 3 x ULN, unless due to disease involvement<br> of the liver or hemolysis, in which case an ALT = 10 x ULN is acceptable<br><br> - Creatinine clearance = 30 mL/min<br><br> - INR = 1.5 x ULN and aPTT . 1.5 x ULN<br><br> 4. For females of childbearing potential, a negative pregnancy test must be documented<br> within 1 week of starting treatment<br><br> 5. Female and male patients who are fertile must agree to use an effective form of<br> contraception (birth control methods while on study, such as birth control pills or<br> injections, intrauterine devices [IUDs]), or double-barrier methods (for example, a<br> condom in combination with spermicide) with their sexual partners for 4 months after<br> the end of treatment<br><br> 6. Signed informed consent<br><br>Exclusion Criteria:<br><br> 1. Patients with Philadelphia chromosome-positive ALL or Burkitt leukemia<br><br> 2. Patients who are willing and eligible to receive intensive chemotherapy (only for<br> patients enrolling in frontline cohort)<br><br> 3. Active serious infection not controlled by oral or intravenous antibiotics<br><br> 4. Known CNS leukemia requiring radiation<br><br> 5. Active GVHD<br><br> 6. Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or<br> squamous cell carcinoma) that in the investigator's opinion will shorten survival to<br> less than 1 year<br><br> 7. Known hepatitis B or C infection, or known seropositivity for human immunodeficiency<br> virus (HIV)<br><br> 8. Active grade III-V cardiac failure as defined by the New York Heart Association<br> Criteria<br><br> 9. Patients with a cardiac ejection fraction (as measured by either multigated<br> acquisition [MUGA] or echocardiogram) < 40%<br><br> 10. Received moderate or strong CYP3A inhibitors or strong CYP3A inducers within 7 days<br> of starting venetoclax<br><br> 11. Received medication that interferes with coagulation or platelet function within 7<br> days prior to the first dose of study drug or during the study treatment period<br><br> 12. Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3<br> days prior to starting venetoclax<br><br> 13. Prior history of treatment with navitoclax.<br><br> 14. Treatment with any investigational antileukemic agents or chemotherapy agents in the<br> last 7 days before study entry, unless full recovery from side effects has occurred<br> or patient has rapidly progressive disease judged to be life-threatening by the<br> investigator. Exception: Treatment with hydroxyurea and/or dexamethasone are allowed<br> prior to study treatment, without window of exclusion<br><br> 15. Pregnant and lactating women will not be eligible; women of childbearing potential<br> should have a negative pregnancy test prior to entering on the study and be willing<br> to practice methods of contraception. Women do not have childbearing potential if<br> they have had a hysterectomy or are postmenopausal without menses for 12 months. In<br> addition, men enrolled on this study should understand the risks to any sexual<br> partner of childbearing potential and should practice an effective method of birth<br> control<br><br> 16. History of significant bleeding disorder unrelated to cancer, including: diagnosed<br> congenital bleeding disorders (e.g., von Willebrand's disease); diagnosed acquired<br> bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)<br><br> 17. Patient with total serum bilirubin > 1.5 x upper limit of normal (ULN).
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Maximum tolerated dose (MTD) (Phase I);DLT (Phase I)
- Secondary Outcome Measures
Name Time Method Overall response rate (Phase II);Minimal residual disease (MRD) negativity;Duration of response (DOR);Event-free survival (EFS);Overall survival (OS);Incidence of adverse events