Safety and Efficacy of Marqibo in Relapsed Acute Lymphoblastic Leukemia

February 8, 2021 updated by: Spectrum Pharmaceuticals, Inc

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The secondary objectives of this study were to evaluate:

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

Study Type

Interventional

Enrollment (Actual)

65

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital
  • Germany
      • Dresden, Germany, 01307
        • Dresden University Hospital
      • Essen, Germany, 45122
        • University of Essen
      • Frankfurt, Germany, 60325
        • J.W. Goethe University
      • Leipzig, Germany
        • University of Leipzig
      • Muenster, Germany, 48149
        • University of Muenster
      • Rostock, Germany, 18057
        • University of Rostock
      • Stuttgart, Germany, 70176
        • Diakonie-Klinikum Stuttgart
      • Stuttgart, Germany
        • Robert Bosch Hospital
      • Ulm, Germany, 89070
        • University of Ulm
  • Israel
      • Haifa, Israel, 31096
        • Rambam Medical Center
      • Jerusalem, Israel, 91120
        • Hadassah Medical Center - Ein Karem
      • Petah-Tikva, Israel, 49100
        • Rabin Medical Center Campus
      • Tel Hashomer, Israel
        • The Chaim Sheba Medical Center
  • United Kingdom
      • Plymouth, United Kingdom, PL6 8DH
        • Derriford Hospital
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
      • Los Angeles, California, United States, 90033
        • USC - Norris Cancer Center
      • San Francisco, California, United States, 94143
        • University of California Medical Center
      • Stanford, California, United States, 94305
        • Stanford Hospitals and Clinics
    • Colorado
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University - Winship Cancer Institute
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
      • Chicago, Illinois, United States, 60153
        • Loyola University Medical Center
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Univesity of Iowa - Hospitals and Clinica
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Medical Center
      • Pittsburgh, Pennsylvania, United States, 15224
        • Western Pennsylvania Allegheny Health System
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas M.D. Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Marqibo
Eligible subjects received study drug at 2.25 mg/m^2 intravenously via peripheral or central venous access over 60 minutes (± 10 minutes).
Drug: 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.
Other Names:
  • VSLI, Vincristine Sulfate Liposomes Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Remission Plus Complete Remission Without Full Platelet Recovery (CR + CRi)
Time Frame: Response assessment performed at the end of each 28 day course.
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.
Response assessment performed at the end of each 28 day course.
Clinical Response Assessment Per Independent Response Review Committee (IRRC) Evaluation
Time Frame: Response assessment at the end of each 28 days course
Number of subjects who achieved Complete Remission (CR)as assessed by the IRRC. CR is defined as no evidence of ALL. ANC>=1X10^9/L or Platelet count>=100x10^9/L, absence of blasts in blood and morrow (<5%), resolution of all sites of extramedullary disease (EMD). CR with incomplete blood count recovery(CRi)is defined as per CR but platelet count <100x10^9/L or ANC<1x10^9/L.
Response assessment at the end of each 28 days course

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of CR + CRi
Time Frame: CR + CRi duration was calculated from the date the subject first met the definition of CR or CRi until the date of relapse
Duration of response for those subjects who achieved CR or CRi
CR + CRi duration was calculated from the date the subject first met the definition of CR or CRi until the date of relapse
Overall Survival
Time Frame: unlimited
Time, in days, from informed consent date until the date of death or date of last contact
unlimited

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Spectrum Pharmaceuticals, Inc

Collaborators

Parexel

Investigators

  • Principal Investigator: Susan O'Brien, MD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (Actual)

August 8, 2010

Study Completion (Actual)

August 8, 2010

Study Registration Dates

First Submitted

June 28, 2007

First Submitted That Met QC Criteria

June 28, 2007

First Posted (Estimate)

July 2, 2007

Study Record Updates

Last Update Posted (Actual)

March 5, 2021

Last Update Submitted That Met QC Criteria

February 8, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HBS407

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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