Safety and Efficacy of Marqibo in Relapsed Acute Lymphoblastic Leukemia

NCT ID: NCT00495079

Last Updated: 2021-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2010-08-08

Brief 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.

Detailed Description

The secondary objectives of this study were to evaluate:

• Duration of CR plus CRi
• Overall survival
• Safety and tolerability

Conditions

Acute Lymphoblastic Leukemia (ALL)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Marqibo

Eligible subjects received study drug at 2.25 mg/m\^2 intravenously via peripheral or central venous access over 60 minutes (± 10 minutes).

Group Type: EXPERIMENTAL

Marqibo® (vincristine sulfate liposomes injection)

Intervention Type: DRUG

Dosing was done every 7 days (± 3 days) on Days 1, 8, 15, and 22 with no less than 4 days between dosing days. Dose calculations were based on body surface area using the subject's height (from Screening) and actual weight for each course.

Interventions

Marqibo® (vincristine sulfate liposomes injection)

Dosing was done every 7 days (± 3 days) on Days 1, 8, 15, and 22 with no less than 4 days between dosing days. Dose calculations were based on body surface area using the subject's height (from Screening) and actual weight for each course.

Intervention Type: DRUG

Other Intervention Names

VSLI, Vincristine Sulfate Liposomes Injection

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

Spectrum Pharmaceuticals, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan O'Brien, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

USC - Norris Cancer Center

Los Angeles, California, United States

UCLA Medical Center

Los Angeles, California, United States

University of California Medical Center

San Francisco, California, United States

Stanford Hospitals and Clinics

Stanford, California, United States

Rocky Mountain Cancer Center

Denver, Colorado, United States

Emory University - Winship Cancer Institute

Atlanta, Georgia, United States

Loyola University Medical Center

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Univesity of Iowa - Hospitals and Clinica

Iowa City, Iowa, United States

Henry Ford Health System

Detroit, Michigan, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

New York Medical College

Valhalla, New York, United States

Western Pennsylvania Allegheny Health System

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Princess Margaret Hospital

Toronto, Ontario, Canada

Dresden University Hospital

Dresden, , Germany

University of Essen

Essen, , Germany

J.W. Goethe University

Frankfurt, , Germany

University of Leipzig

Leipzig, , Germany

University of Muenster

Münster, , Germany

University of Rostock

Rostock, , Germany

Diakonie-Klinikum Stuttgart

Stuttgart, , Germany

Robert Bosch Hospital

Stuttgart, , Germany

University of Ulm

Ulm, , Germany

Rambam Medical Center

Haifa, , Israel

Hadassah Medical Center - Ein Karem

Jerusalem, , Israel

Rabin Medical Center Campus

Petah Tikva, , Israel

The Chaim Sheba Medical Center

Tel Litwinsky, , Israel

Derriford Hospital

Plymouth, , United Kingdom

Countries

United States; Canada; Germany; Israel; United Kingdom

References

Schiller GJ, Damon LE, Coutre SE, Hsu P, Bhat G, Douer D. High-Dose Vincristine Sulfate Liposome Injection, for Advanced, Relapsed, or Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in an Adolescent and Young Adult Subgroup of a Phase 2 Clinical Trial. J Adolesc Young Adult Oncol. 2018 Oct;7(5):546-552. doi: 10.1089/jayao.2018.0041. Epub 2018 Sep 21.

Reference Type: DERIVED

PMID: 30239252 (View on PubMed)

Silverman JA, Reynolds L, Deitcher SR. Pharmacokinetics and pharmacodynamics of vincristine sulfate liposome injection (VSLI) in adults with acute lymphoblastic leukemia. J Clin Pharmacol. 2013 Nov;53(11):1139-45. doi: 10.1002/jcph.155. Epub 2013 Aug 17.

Reference Type: DERIVED

PMID: 23907766 (View on PubMed)

O'Brien S, Schiller G, Lister J, Damon L, Goldberg S, Aulitzky W, Ben-Yehuda D, Stock W, Coutre S, Douer D, Heffner LT, Larson M, Seiter K, Smith S, Assouline S, Kuriakose P, Maness L, Nagler A, Rowe J, Schaich M, Shpilberg O, Yee K, Schmieder G, Silverman JA, Thomas D, Deitcher SR, Kantarjian H. High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia. J Clin Oncol. 2013 Feb 20;31(6):676-83. doi: 10.1200/JCO.2012.46.2309. Epub 2012 Nov 19.

Reference Type: DERIVED

PMID: 23169518 (View on PubMed)

Other Identifiers

HBS407

Identifier Type: -

Identifier Source: org_study_id