A Phase 3 Study to Evaluate Marqibo® in the Treatment of Subjects ≥ 60 Years Old With Newly Diagnosed ALL

A phase 3, multicenter, randomized study to evaluate the substitution of Marqibo®
(Vincristine Sulfate Liposomes Injection, VSLI) for standard Vincristine Sulfate Injection
(VSI) in the induction, intensification, and maintenance phases of combination chemotherapy
in the treatment of subjects >or= 60 years old with newly diagnosed acute lymphoblastic
leukemia (ALL).

Inclusion Criteria:

Have provided written, signed, and dated informed consent to participate in the study, in
accordance with the ICH GCP Guideline E6 and all applicable local regulations.Are age
>or=60 years (at the time of providing informed consent).

Have newly diagnosed, histologically proven, untreated Philadelphia chromosome-negative
(Ph-) ALL, with >or= 5% bone marrow blasts.

Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Have a life
expectancy >or= 3 months.

Have renal and liver function as defined below within 14 days, inclusive, prior to study
enrollment, unless the abnormality is considered attributable to leukemia:

Total bilirubin ≤ 2.0 x the upper limit of normal (ULN), unless the subject has a known
diagnosis of Gilbert's disease Aspartate transaminase (AST, SGOT) or alanine transaminase
(ALT, SGPT) ≤ 3 x ULN Serum creatinine ≤ 1.5 x ULN. Not have had major surgery within 4
weeks before the planned start of treatment.

If female, are post-menopausal, surgically sterilized, or willing to use acceptable
methods of birth control (eg, hormonal contraceptive, intra-uterine device, diaphragm with
spermicide, condom with spermicide, or abstinence) from the screening visit through 30
days after the last dose of any protocol defined chemotherapeutic agents.

If male and sexually active with a partner of child-bearing potential, agree to use an
acceptable barrier method for contraception from the screening visit through 30 days after
the last dose of any protocol defined chemotherapeutic agents.

Have the ability and willingness to fully comply with study procedures and restrictions.

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Exclusion Criteria:

Has had prior systemic chemotherapy (for ALL or other malignancy). Has had prior
vincristine for any reason. Is planning to undergo stem cell transplantation (SCT) as any
part of first-line therapy for ALL.

Has Burkitt's lymphoma/leukemia. Has Philadelphia chromosome-positive (Ph+) ALL and/or
BCR/ABL rearrangements documented by fluorescent in-situ hybridization (FISH),
cytogenetics, or polymerase chain reaction (PCR).

Has active central nervous system (CNS) disease. Has ongoing neuropathy of any etiology >
Grade 1. Has a history of persistent active neurologic disorders including demyelinating
form of Charcot-Marie-Tooth syndrome, acquired demyelinating disorders, and other
demyelinating conditions.

Prior hydroxyurea (Hydrea®) for the management of any condition other than leukocytosis or
prior hydroxyurea of >7 days duration for the management of leukocytosis (hydroxyurea for
the management of leukocytosis must be planned to be tapered off before or on Day 5 of
Induction).

Has received prior steroids within 7 days before beginning protocol-specified Induction
therapy for reasons other than leukocytosis (steroids for the management of leukocytosis
are allowed but must be planned to be tapered off before or on Day 5 of Induction).

Has an active serious infection not controlled by oral or IV antibiotics or antifungals.

Has received any investigational therapy within 28 days before beginning any
protocol-defined chemotherapeutic treatment.

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