This is a pilot study utilizing Marqibo® (vincristine sulfate liposome injection) combined with dexamethasone, mitoxantrone and asparaginase (UK ALL R3) for relapsed acute lymphoblastic leukemia (ALL).
A Pilot Study of Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapse of Acute Lymphoblastic Leukemia
This study will utilize Marqibo® as a replacement for standard vincristine in combination with UK ALL R3 induction for children with relapsed ALL. The hypothesis is that the incorporation of Marqibo® with combination chemotherapy will be safe and feasible. In the context of this pilot study, overall outcomes and efficacy will be a secondary objective. It is hypothesized that data from this combination may show improved efficacy including, complete remission (CR), minimal residual disease (MRD) negativity, and progression free survival (PFS) rates and safety (i.e., neurotoxicity) in comparison to outcomes in historical regimens, including the UK ALL R3 with standard vincristine.
ALL, Childhood Lymphoblastic Leukemia, Acute, Childhood Lymphoblastic Leukemia, Acute Vincristine
For people ages 1 year to 21 years
Inclusion Eligibility Criteria
Age Patients must be ≥ 1 and ≤ 21 years of age at the time of enrollment.
Diagnosis Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) with ≥ 5%blasts in the bone marrow (M2 or M3), with or without extramedullary disease (excluding active Central Nervous System 3 involvement).
Subjects with first relapse must have an M3 marrow to be eligible.
Performance Level Karnofsky> 50% for patients> 16 years of age and Lansky> 50% for patients ≤ 16 years of age.
Patients who relapse while on maintenance-type ALL therapy or are receiving maintenance therapy for disease stabilization will not require a wash-out period before entry into this study. However, there must be at least 14 days after any dose of standard vincristine.
Renal and Hepatic Function
Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST)must be < 3 x institutional upper limit of norm ULN. Total bilirubin must be ≤ 1.5 x ULN (except in the case of subjects with documented Gilbert's disease ≤ 5 × ULN).
Cardiac Function Patients must have a shortening fraction ≥ 27% or an ejection fraction ≥55% by echocardiogram, cardiac MRI or multigated acquisition scan (MUGA).
Male and female patients of childbearing potential must agree to use an effective method of contraception during the study.
Exclusion Eligibility Criteria
Patients will be excluded if they have active Central Nervous System (CNS) 3 status.
Patients will be excluded if they have isolated testicular disease.
Patients with biphenotypic leukemia will be excluded.
Patients will be excluded if they have refractory disease or fourth relapse and beyond,defined as any of the following:
Failing to go into remission from original diagnosis after two previous induction attempts.
Patients will be excluded if they have previously received Marqibo®.
Patients will be excluded if they have a known allergy to any of the drugs used in the study, with the exception that patients with an allergy to PEG-asparaginase who can receive Erwinia are eligible.
Patients will be excluded if they have active, uncontrolled systemic fungal, bacterial,viral or other infection despite appropriate antibiotics or other treatment.
Patients who require azole antifungal agents will be excluded. Azoles must be discontinued at least one week prior to the start of Marqibo®.
Patients will be excluded if there is a plan to administer non-protocol chemotherapy,radiation therapy, another investigational agent or immunotherapy during the study period.
Patients with pre-existing, persistent grade 2 or greater sensory or motor neuropathy from any cause will be excluded.
Patients will be excluded if they have Down syndrome, significant concurrent disease,illness, psychiatric disorder or social issue that would compromise patient safety or adherence with the protocol treatment or procedures or interfere with consent, study participation, follow up, or interpretation of study results.
Patients positive for human immunodeficiency virus (HIV) will be excluded due to the increased risk of complications such as severe infection and unknown interaction of Marqibo® with antiretroviral drugs.
Active hepatitis B or C infection as defined by seropositive for hepatitis B (hepatitis B surface antigen (HBsAg)) or hepatitis C and elevated liver transaminases (defined as above the ULN per the institution normal ranges).
We will not share your information with anyone other than the team in charge of this study. Submitting your contact information does not obligate you to participate in research.
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If you do not hear from the study team, please call 888-689-8273 and tell them you’re interested in study number NCT02879643.
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