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

Study Overview
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Brief Summary
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A phase 3 study in the treatment of subjects >or= 60 years old with newly diagnosed acute lymphoblastic leukemia (ALL).

Detailed Description
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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).

Official Title
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Phase 3 Study of Study to Evaluate Marqibo® in the Combination Chemotherapy in the Treatment of Subjects >or=60 Years Old With Newly Diagnosed Acute Lymphoblastic Leukemia (ALL)

Conditions
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Acute Lymphoblastic Leukemia (ALL)

Intervention / Treatment
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* Drug: Vincristine Sulfate Liposomes Injection (VSLI)
* Drug: Vincristine Sulfate Injection (VSI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have provided written, signed, and dated informed consent to participate in the study, in accordance with the International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice (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-) Acute lymphocytic leukemia [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, Serum glutamic oxaloacetic transaminase [SGOT]) or alanine transaminase (ALT, Serum glutamic pyruvic transaminase [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. - 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. -

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vincristine Sulfate Injection (VSI)<br>VSI dosed at 1.4 mg/m^2 with a 2 mg dose cap as an intravenous (IV) infusion over 10 minutes. | Drug: Vincristine Sulfate Injection (VSI)<br>* 1.4 mg/m^2 with a 2 mg dose cap as an IV infusion over 10 minutes.<br>* Other names: Vincristine;|
| Experimental: Marqibo<br>Marqibo dosed at 2.25 mg/m^2 (without any dose cap) as an IV infusion over 60 minutes. | Drug: Vincristine Sulfate Liposomes Injection (VSLI)<br>* 2.25 mg/m^2 (without any dose cap) as an IV infusion over 60 minutes.<br>* Other names: Marqibo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival was defined as the time from the date of study randomization until death from any cause. Observations censored at the date of the last follow-up for subjects not known to have died. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALL, Marqibo, HALLMARQ, leukemia, front-line, acute lymphoblastic leukemia