CXCR4 Antagonist BL-8040 and Nelarabine in Treating Patients with Relapsed or Refractory T-Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
- Diagnosis of T-acute lymphoblastic leukemia/ lymphoblastic lymphoma according to World Health Organization (WHO) criteria which has relapsed or is refractory to chemotherapy
- Peripheral blood lymphoblasts =< 50,000 mcL; hydroxyurea and/or leukapheresis is permitted to reduce the peripheral blast count prior to enrollment and treatment
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Calculated creatinine clearance >= 50 ml/min using the Cockcroft-Gault formula
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2 x institutional upper limit of normal (IULN) except for Gilbert’s disease or when in the opinion of treating physician elevated levels are due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia), in which case ALT and AST may be elevated up to =< 5 x IULN
- Total bilirubin =< 2 x institutional upper limit of normal (IULN) except for Gilbert’s disease or when in the opinion of treating physician elevated levels are due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia)
- Women of childbearing potential and men must agree to use adequate contraception with a highly effective method (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation; abstinence is acceptable if this is the established and preferred contraception for the subject
- Female subjects must have a negative urine or serum pregnancy test within 72 hours prior to start of study treatment if of childbearing potential or be of non-childbearing potential; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; the serum pregnancy test must be negative for the subject to be eligible; non-childbearing potential is defined as: * >= 45 years of age and has not had menses for > 2 years * Amenorrheic for > 2 years without a hysterectomy and oophorectomy and a follicle stimulating hormone (FSH) value in the postmenopausal range upon pretrial (screening) evaluation * Post-hysterectomy, oophorectomy, or tubal ligation; documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound; tubal ligation must be confirmed with medical records of the actual procedure
- Able to understand and willing to sign an Institutional Review Board (IRB)-approved written informed consent document
- Previous treatment with nelarabine for relapsed or refractory disease
- Pregnant or nursing
- Received any other investigational agent or systemic cytotoxic chemotherapy within the preceding 2 weeks
- Active central nervous system (CNS) involvement with leukemia
- Active human immunodeficiency virus (HIV) or hepatitis B or C infection
- Any medical condition which, in the opinion of the clinical investigator, would interfere with the evaluation of the patient; subjects with a clinically significant or unstable medical or surgical condition or any other condition that cannot be well-controlled by the allowed medications permitted in the study protocol that would preclude safe and complete study participation, as determined by medical history, physical examinations, laboratory tests, and according to the investigator’s judgment
I. To assess the safety and tolerability of CXCR4 antagonist BL-8040 (BL-8040) when administered with nelarabine in patients with T-cell acute lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (LBL).
I. To describe the pharmacodynamic effects of BL-8040 on T-lymphoblasts in including inhibition of CXCR4 signaling on lymphoblasts, mobilization of lymphoblasts into the peripheral circulation, induction of apoptosis in lymphoblasts, and alterations in lymphoblast cell cycle status.
II. To estimate the composite complete remission (cytogenetic complete response [CRc] = complete response [CR] + morphologic complete remission with incomplete bone marrow recovery [CRi]) and the overall response rate (CR, CRi + partial remission [PR]) for patients with T-ALL/LBL treated with the combination of BL-8040 plus nelarabine.
III. To determine the time to response, duration of response, disease-free, event-free and overall survival of patients treated with BL-8040 plus nelarabine.
IV. To estimate the rate of patients who proceed to allogenic hematopoietic cell transplant (alloHCT) after treatment.
V. To describe the interaction of pretreatment disease and patient characteristics including morphology, CXCR4 expression on lymphoblasts, cytogenetics, immunophenotype, white blood cell counts (WBC), and performance status on clinical outcomes.
Patients receive CXCR4 antagonist BL-8040 subcutaneously (SC) on days 1-6 of course 1 and days 1-5 of subsequent courses. Patients also receive nelarabine intravenously (IV) over 2 hours on days 2, 4, and 6 of course 1 and days 1, 3, and 5 of subsequent courses. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity
After completion of study treatment, patients are followed up for 30 days and then every 3 months for up to 2 years.
Trial Phase Phase II
Trial Type Treatment
Siteman Cancer Center at Washington University
Geoffrey L. Uy
- Primary ID 201606146
- Secondary IDs NCI-2016-01051
- Clinicaltrials.gov ID NCT02763384