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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


Phase 2
18 Years
N/A
Not Enrolling
Both
Acute Lymphoblastic Leukemia (ALL)

Thank you

Trial Information

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


The secondary objectives of this study were to evaluate:

- Duration of CR plus CRi

- Overall survival

- Safety and tolerability


Inclusion Criteria:



- Age ≥18 years.

- Had Ph- ALL or lymphoblastic lymphoma and was in second relapse, or had failed 2
treatment lines of anti-leukemia chemotherapy.

- Had histologically or cytologically proven ALL and ≥ 10% bone marrow blasts. If < 10%
bone marrow blasts, subject must have had histologically or cytologically proven ALL
and evaluable extramedullary disease. Sponsor approval was obtained prior to
enrolling subjects who had < 10% bone marrow blasts with evaluable extramedullary
disease.

- Had achieved a CR to at least 1 prior anti-leukemia therapy as defined by a
leukemia-free interval of ≥ 90 days.

- For subjects with a prior history of stem cell transplantation, had ≤ Grade 1 active
skin graft-versus-host disease (GVHD). No active gastrointestinal or liver
graft-versus-host disease.

- Had an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3.

- Had normal renal and liver function as defined below within 14 days, inclusive, prior
to first dose of VSLI, unless the abnormality was considered attributable to
leukemia:

- Total bilirubin ≤ 2.0 × institutional upper limit of normal, unless the subject
had a known diagnosis of Gilbert's disease. If a subject had Gilbert's disease,
he/she could have participated in this study, however must have been monitored
closely during the study.

- Aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3 × institutional
upper limit of normal.

- Serum creatinine ≤ 2.0 g/dL or calculated estimated creatinine clearance ≥ 50
mL/minute/1.73 m2 based on Cockcroft and Gault formula, unless renal dysfunction
was considered due to hematologic malignancy.

- Had never received prior VSLI treatment.

- For women of childbearing potential, had a negative serum or urine pregnancy test
within 14 days prior to enrollment.

- If female, the subject was postmenopausal, surgically sterilized, or willing to use
acceptable methods of birth control (e.g., hormonal contraceptive, intra-uterine
device, diaphragm with spermicide, and condom with spermicide or abstinence) from the
Screening visit through 30 days after the last dose of VSLI.

- If male, the subject agreed to use an acceptable barrier method for contraception
from the Screening visit through 30 days after the last dose of VSLI.

- Before enrollment, the subject was 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.

Exclusion Criteria:

- Had Burkitt's lymphoma or Burkitt's leukemia.

- Had a history of Philadelphia chromosome-positive (Ph+) ALL and/or BCR/ABL
rearrangements documented by fluorescent in situ hybridization or polymerase chain
reaction.

- Had a history of Philadelphia chromosome-positive (Ph+) ALL and/or BCR/ABL
rearrangements documented by fluorescent in situ hybridization or polymerase chain
reaction.

- Had active CNS disease. History of treated CNS disease was allowable. The CNS disease
must have resolved in order for the subject to be eligible.

- Was eligible for stem cell transplantation. This implied that a suitable donor was
readily available, the subject was willing to undergo stem cell transplantation, and
the Investigator believed this was a better treatment option than VSLI. This was at
the Investigator's discretion.

- Was treated with any investigational agents or chemotherapy agents in the last 21
days before the first dose of VSLI, unless full recovery from side effects had
occurred or the subject had rapidly progressing disease judged to be life threatening
by the Investigator.

- Was receiving any other standard or investigational treatment for the subject's
leukemia.

- Intrathecal chemotherapy for CNS prophylaxis was allowable.

- The use of hydroxyurea (Hydrea®) to control leukocytosis was allowable but must
have been tapered off by Day 14 of Course 1. From Day 15 of Course 1 on through
the end of study participation, hydroxyurea (Hydrea®) was not allowed.

- 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 were not
allowed.

- Had persistent chronic clinically significant toxicities from prior chemotherapy ≥
Grade 2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse
Events [CTCAE] version 3.0).

- Had persistent ≥ Grade 2 active neuropathy (NCI CTCAE v3.0).

- Had 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).

- Had a history of allergic reactions or sensitivity attributed to compounds of similar
chemical or biologic composition to vincristine or components of study drug.

- Was female who was pregnant or breast-feeding.

- Had active serious infection not controlled by oral or intravenous antibiotics or
antifungals.

- Had human immunodeficiency virus positive status.

- Had any medical condition which in the opinion of the investigator placed the subject
at an unacceptably high risk for toxicities.

- Had 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete Remission Plus Complete Remission Without Full Platelet Recovery (CR + CRi)

Outcome Description:

CR is defined as no evidence of ALL: ANC>or=1x10^9/L or platelet count>100x10^9/L, absence of leukemia blast cells in blood and marrow (<5% blasts), resolution of all sites of extramedullary disease (EMD). CR with incomplete blood count recovery (CRi): As per CR but platelet count< 100x10^9/L or ANC< 1x10^9/L. Partial remission(PR):CR with>5-25% abnormal cells in the marrow or 50% decrease in bone marrow blasts. Reduction in EMD by at least 50%. Hematologic Improvement. Bone marrow blast(BMB) response: BMB<5% in the absence of HI. Stable disease(SD):No significant hematological and extramedullary change from baseline.

Outcome Time Frame:

Response assessment performed at the end of each 28 day course.

Safety Issue:

No

Principal Investigator

Susan O'Brien, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

HBS407

NCT ID:

NCT00495079

Start Date:

May 2007

Completion Date:

March 2011

Related Keywords:

  • Acute Lymphoblastic Leukemia (ALL)
  • acute
  • lymphoblastic
  • lymphocytic
  • leukemia
  • leukaemia
  • lukemia
  • leukimia
  • ALL
  • Marqibo
  • Hana Biosciences
  • vincristine
  • liposomal
  • liposome
  • optisome
  • hematology
  • malignancy
  • hematological
  • relapsed
  • anti-leukemia
  • adult
  • chemotherapy
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Philadelphia Chromosome

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Loyola University Medical CenterMaywood, Illinois  60153
New York Medical CollegeValhalla, New York  10595
Rush University Medical CenterChicago, Illinois  60612-3824
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330
Hackensack University Medical CenterHackensack, New Jersey  07601
Rocky Mountain Cancer CenterDenver, Colorado  80218
University of Pittsburgh Medical CenterPittsburgh, Pennsylvania  15213
Henry Ford Health SystemDetroit, Michigan  48202
University of Chicago Medical CenterChicago, Illinois  60637
UCLA Medical CenterLos Angeles, California  90095-7059
University of Texas M.D. Anderson Cancer CenterHouston, Texas  77030
USC - Norris Cancer CenterLos Angeles, California  90033
Emory University - Winship Cancer InstituteAtlanta, Georgia  30322-1013
University of California Medical CenterSan Francisco, California  94143
Stanford Hospitals and ClinicsStanford, California  94305
Univesity of Iowa - Hospitals and ClinicaIowa City, Iowa  52242
Western Pennsylvania Allegheny Health SystemPittsburgh, Pennsylvania  15224