A Phase 2 Study to Evaluate the Safety and Efficacy of Weekly Doses of Marqibo® (vincristine sulfate liposomes injection) in Adult Patients with Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia (ALL) in Second Relapse or Adult Patients with Philadelphia Chromosome-negative ALL Who Failed Two Treatment Lines of Anti-leukemia Chemotherapy

• Conditions: Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia; MedDRA version: 9.1Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemia

• Registration Number: EUCTR2006-006978-20-GB
• Lead Sponsor: Hana Biosciences, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-12-14
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

1. Age =18 years.
2 Have Philadelphia chromosome-negative ALL or lymphoblastic lymphoma
and be in second relapse or have failed two treatment lines of anti-leukemia
chemotherapy.
3 Have histologically or cytologically proven ALL and =10% bone marrow
blasts. If < 10% bone marrow blasts, subject must have histologically or
cytologically proven ALL and evaluable extramedullary disease.
4 Have achieved a complete response to at least one prior anti-leukemia therapy
as defined by a leukemia-free interval of = 90 days.
5 For subjects with a prior history of stem cell transplantation, have a 6 Have ECOG performance status 0–3.
7. Have normal renal and liver function as defined below within 14 days, inclusive, prior to first dose of Marqibo, unless the abnormality is considered attributable to leukemia:
a. Total bilirubin =2.0 x institutional upper limit of normal (ULN), unless the subject
has a known diagnosis of Gilbert’s disease. If a subject has Gilbert’s disease, he/she
can participate in this study, however must be monitored closely during the study.
b. Aspartate transaminase (AST, SGOT) or alanine transaminase (ALT, SGPT) =3 x
institutional ULN.
c. Serum creatinine =2.0 g/dL or calculated estimated creatinine clearance =50
mL/min/1.73 m2 based on Cockcroft and Gault formula, unless renal dysfunction is
considered due to hematologic malignancy.
8. Have never received prior Marqibo treatment.
9. For women of childbearing potential, have a negative serum or urine pregnancy test within 14 days prior to enrollment.
10. If female, the subject is post-menopausal, surgically sterilized, or willing to use
acceptable methods of birth control (e.g., 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 Marqibo.
11. If male, the subject agrees to use an acceptable barrier method for ontraception from the Screening visit through 30 days after the last dose of Marqibo.
12. Before enrollment, the subject is capable of understanding and complying with
parameters as outlined in the protocol and able to sign a written informed consent
according to ICH/GCP, and national/local regulations.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Have Burkitt’s lymphoma or Burkitt’s leukemia
2. Have a history of Philadelphia chromosome-positive ALL and/or BCR/ABL
rearrangements documented by FISH or PCR.
3. Have active CNS disease. History of treated CNS disease is allowable. The CNS disease
must have resolved in order for the subject to be eligible.
4. Are eligible for stem cell transplantation. This implies that a suitable donor is readily available, the subject is willing to undergo stem cell transplantation, and the Investigator believes this is a better treatment option than Marqibo. This is at the Investigator’s discretion.
5. Are treated with any investigational agents or chemotherapy agents in the last 21 days before the first dose of Marqibo, unless full recovery from side effects has occurred or the subject has rapidly progressing disease judged to be life threatening by the Investigator.
6. Are receiving any other standard or investigational treatment for their leukemia.
a. Intrathecal chemotherapy for CNS prophylaxis is allowable.
b. The use of hydroxyurea (Hydrea®) to control leukocytosis is allowable but must be
tapered off by Day 14 of Course 1. From Day 15 of Course 1 on through the end of
study participation, hydroxyurea (Hydrea®) is not allowed.
c. Systemic corticosteroids must have been tapered off, preferably before the start of
study treatment, but no later than by Day 5 of Course 1. From Day 6 of Course 1 on
through the end of study participation, systemic corticosteroids are not allowed.
7. Have persistent chronic clinically significant toxicities from prior chemotherapy =Grade 2 (NCI CTCAE v3.0).
8. Have persistent =Grade 2 active neuropathy (NCI CTCAE v3.0).
9. Have a history of persistent =Grade 2 active neurologic disorders unrelated to
chemotherapy (including demyelinating form of Charcot-Marie-Tooth syndrome,
acquired demyelinating disorders, or other demyelinating condition).
10. Have a history of allergic reactions or sensitivity attributed to compounds of similar chemical or biologic composition to vincristine or components of Marqibo (vincristine sulfate injection, sphingomyelin/cholesterol liposomes, sodium phosphate injection).
11. Are pregnant or breast-feeding women.
12. Have active serious infection not controlled by oral or intravenous antibiotics or
antifungals.
13. Have human immunodeficiency virus (HIV) positive status.
14. Have any medical condition which in the opinion of the Investigator places the subject at an unacceptably high risk for toxicities.
15. Have any condition or circumstance which in the opinion of the Investigator would
significantly interfere with the subject’s protocol compliance and put the subject at
increased risk.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of the study treatment as determined by the rate of complete remission (CR) and complete remission with incomplete blood count recovery (CRi) in adult subjects with Philadelphia chromosome-negative ALL in second relapse or adult subjects with Philadelphia chromosome-negative ALL or Lymphoblastic Lymphoma who failed two treatment lines of antileukemia chemotherapy. One of these leukemia free intervals must be defined as lasting >90 days. ;Secondary Objective: The secondary objectives of this study are to evaluate:<br>- duration of CR and CRi<br>- overall survival<br>- safety and tolerability;Primary end point(s): The primary efficacy endpoint is complete remission (CR) plus complete remission with incomplete blood count recovery (CRi).