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Safety and Efficacy of Marqibo in Relapsed Acute Lymphoblastic Leukemia

Information source: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Acute Lymphoblastic Leukemia (ALL)

Intervention: Marqibo® (vincristine sulfate liposomes injection) (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Spectrum Pharmaceuticals, Inc

Official(s) and/or principal investigator(s):
Susan O'Brien, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

Summary

This was a Phase 2, international, multicenter, open-label, single-arm trial evaluating Marqibo (VSLI) in adult subjects with: 1) Ph- ALL or lymphoblastic lymphoma in second or greater relapse; or 2) Ph- ALL or lymphoblastic lymphoma who failed 2 or greater treatment lines of anti-leukemia chemotherapy. The original enrollment target for this study was approximately 56 subjects. Per a protocol amendment, enrollment was increased from 56 to 65. The primary objective of this study was to evaluate:

- The efficacy of the study treatment as determined by the rate of CR plus CR with

incomplete blood count recovery (CRi) in adult subjects with Philadelphia chromosome-negative (Ph-) ALL in second relapse or adult subjects with (Ph-) ALL who failed 2 treatment lines of anti-leukemia chemotherapy. Subjects must have achieved a CR to at least 1 prior anti-leukemia therapy as defined by a leukemia-free interval of ≥ 90 days.

Clinical Details

Official title: 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

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

Primary outcome:

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

Clinical Response Assessment Per Independent Response Review Committee (IRRC) Evaluation

Secondary outcome:

Duration of CR + CRi

Overall Survival

Detailed description: The secondary objectives of this study were to evaluate:

- Duration of CR plus CRi

- Overall survival

- Safety and tolerability

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Locations and Contacts

Dresden University Hospital, Dresden 01307, Germany

University of Essen, Essen 45122, Germany

J.W. Goethe University, Frankfurt 60325, Germany

University of Leipzig, Leipzig, Germany

University of Muenster, Muenster 48149, Germany

University of Rostock, Rostock 18057, Germany

Diakonie-Klinikum Stuttgart, Stuttgart 70176, Germany

Robert Bosch Hospital, Stuttgart, Germany

University of Ulm, Ulm 89070, Germany

Rambam Medical Center, Haifa 31096, Israel

Hadassah Medical Center - Ein Karem, Jerusalem 91120, Israel

Rabin Medical Center Campus, Petah-Tikva 49100, Israel

The Chaim Sheba Medical Center, Tel Hashomer, Israel

Derriford Hospital, Plymouth PL6 8DH, United Kingdom

UCLA Medical Center, Los Angeles, California 90095, United States

USC - Norris Cancer Center, Los Angeles, California 90033, United States

University of California Medical Center, San Francisco, California 94143, United States

Stanford Hospitals and Clinics, Stanford, California 94305, United States

Rocky Mountain Cancer Center, Denver, Colorado 80218, United States

Emory University - Winship Cancer Institute, Atlanta, Georgia 30322, United States

Loyola University Medical Center, Chicago, Illinois 60153, United States

Rush University Medical Center, Chicago, Illinois 60612, United States

University of Chicago Medical Center, Chicago, Illinois 60637, United States

Univesity of Iowa - Hospitals and Clinica, Iowa City, Iowa 52242, United States

Henry Ford Health System, Detroit, Michigan 48202, United States

University of Nebraska Medical Center, Omaha, Nebraska 68198, United States

Hackensack University Medical Center, Hackensack, New Jersey 07601, United States

Roswell Park Cancer Institute, Buffalo, New York 14263, United States

New York Medical College, Valhalla, New York 10595, United States

Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada

University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15232, United States

Western Pennsylvania Allegheny Health System, Pittsburgh, Pennsylvania 15224, United States

University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, United States

Additional Information

Starting date: May 2007
Last updated: December 2, 2013

Page last updated: August 23, 2015

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