Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy

NCT02879643 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: T2012-002
• Study Type: interventional
• Target: 29
• Locations: 3 countries
• Sites: 35

Brief Summary

This is a pilot study utilizing Marqibo® (vincristine sulfate liposome injection) combined with dexamethasone, mitoxantrone and asparaginase (UK ALL R3) for relapsed acute lymphoblastic leukemia (ALL).

Conditions

ALL, Childhood; Lymphoblastic Leukemia, Acute, Childhood; Lymphoblastic Leukemia, Acute

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicities as a Measure of Safety and Tolerability

  Number of Participants with Dose Limiting Toxicities as a Measure of Safety and Tolerability at different dose levels of Marqibo. Dose Level 1 = 1.5 mg/m\^2. Dose Level 2 = 2.0 mg/m\^2. Cohort A and B accrued at both Dose Levels. Cohort C accrued only at Dose Level 2.

  9 weeks

Study Arms (3)

Cohort A: Marqibo and UK ALL R3 backbone

EXPERIMENTAL

* Marqibo®: given by intravenous (IV) infusion on days 1, 8, 15 and 22. * Dexamethasone orally twice daily on days 1-5 and 15-19. * Mitoxantrone: given by intravenous (IV) infusion on days 1 and 2. * PEG-asparaginase: given as an injection into the muscle on says 3 and 17. * Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8.

Drug: Marqibo

Cohort B: Marqibo and lower intensity UK ALL R3 backbone

EXPERIMENTAL

* Marqibo®: given by intravenous (IV) infusion on days 1, 8, 15 and 22. * Dexamethasone orally twice daily on days 1-5 and 15-19. * PEG-asparaginase: given as an injection into the muscle on days 3 and 17. * Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8.

Drug: Marqibo

Cohort C: Marqibo and maintenance regimen

EXPERIMENTAL

* Marqibo®: given by intravenous (IV) infusion on day 1 * Dexamethasone orally twice daily on days 1-5 * Methotrexate: given orally on days 1 and 8 * Mercaptopurine: given orally daily on days 1-13

Drug: Marqibo

Interventions

Marqibo DRUG

The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.

Cohort A: Marqibo and UK ALL R3 backbone; Cohort B: Marqibo and lower intensity UK ALL R3 backbone; Cohort C: Marqibo and maintenance regimen

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age
• Patients must be ≥ 1 and ≤ 21 years of age at the time of enrollment.
• Diagnosis
• Cohort A: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) or mixed phenotypic acute leukemia with ≥ 5% blasts in the bone marrow (M2 or M3), with or without extramedullary disease) or a diagnosis of lymphoblastic lymphoma.
• Cohorts B \& C: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma, or mixed phenotypic acute leukemia with any level of detectable disease (minimal residual disease level acceptable) with or without extramedullary disease
• Performance Level -Karnofsky \> 50% for patients \> 16 years of age and Lansky \> 50% for patients ≤ 16 years of age.
• Prior Therapy
• Patients must have recovered from the acute toxic effects (≤ Grade 2 or baseline) of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, unless otherwise specified. Subjects with disease related cytopenias will be eligible.
• Patients must have relapsed or refractory disease after attaining at least a first remission. They may be in first to third relapse..
• Patients with Philadelphia chromosome t(9;22) positive disease must have received at least two prior tyrosine kinase inhibitors.
• Patients who have experienced their relapse after a Hematopoietic stem cell transplantation (HSCT) are eligible, provided they have no evidence of graft-versus-host disease (GVHD) and are at least 100 days post-transplant at the time of enrollment.
• Prior anthracycline lifetime cumulative exposure: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy.
• Cohort A: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy (See Appendix 2 for anthracycline calculation worksheet).
• Cohorts B \& C: There is no limit on prior anthracycline exposure.
• Hematopoietic growth factors: It must have been at least seven days since the completion of therapy with granulocyte colony-stimulating factor (GCSF) or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).

You may not qualify if:

• Patients will be excluded if they have isolated testicular disease.
• Patients will be excluded if they have previously received Marqibo®.
• Patients will be excluded if they have a known allergy to any of the drugs used in the study, with the exception that patients with an allergy to PEG-asparaginase who can receive Erwinia asparaginase are eligible. Patients unable to receive any formulation of asparaginase may only enroll on cohort C
• Patients will be excluded if they have active, uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment.
• Patients who require azole antifungal agents will be excluded. Azoles must be discontinued at least one week prior to the start of Marqibo®.
• Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, another investigational agent or immunotherapy during the study period.
• Patients with pre-existing, persistent grade 2 or greater sensory or motor neuropathy from any cause will be excluded.
• Patients will be excluded if they have, significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or adherence with the protocol treatment or procedures or interfere with consent, study participation, follow up, or interpretation of study results.Patients with Down syndrome will not be eligible for enrollment on Cohort A
• Patients with a known history of human immunodeficiency virus (HIV) will will be excluded due to the increased risk of complications such as severe infection and unknown interaction of Marqibo® with antiretroviral drugs.
• Active hepatitis B or C infection as defined by seropositive for hepatitis B (hepatitis B surface antigen (HBsAg)) or hepatitis C and elevated liver transaminases (defined as above the ULN per the institution normal ranges).

Sponsors & Collaborators

• Therapeutic Advances in Childhood Leukemia Consortium: lead
• Spectrum Pharmaceuticals, Inc: collaborator

Study Sites (35)

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Orange County

Orange, California, 92868, United States

Location

UCSF School of Medicine

San Francisco, California, 94158, United States

Location

The Children's Hospital, University of Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Children's Healthcare of Atlanta at Egleston

Atlanta, Georgia, 30322, United States

Location

Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Sidney Kimmel Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

National Cancer Institute, Pediatric Oncology Branch

Bethesda, Maryland, 20892, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

CS Mott Children's Hospital, Ann Arbor

Ann Arbor, Michigan, 48109, United States

Location

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Children's Hospital New York-Presbyterian

New York, New York, 10032, United States

Location

Levine Children's Hospital

Charlotte, North Carolina, 28203, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Rainbow Babies & Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Texas Children's Cancer Center, Baylor

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia

Location

The Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia

Location

Lady Cilento Children's Hospital

South Brisbane, Queensland, 4101, Australia

Location

Royal Children's Hospital, Melbourne

Parkville, Victoria, 3052, Australia

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Sainte-Justine University Hospital Center

Montréal, Québec, H3T-1C5, Canada

Location

Related Publications (1)

• Shah NN, Schafer ES, Chi YY, Malvar J, Heym KM, Place AE, Burns M, Chang BH, Slone T, Verma A, Gossai N, Shaw PH, Burke MJ, Hermiston M, Schore RJ, Cooper T, Pauly M, Rushing T, Jarosinski P, Florendo E, Yates B, Widemann BC, Peer CJ, Figg WD, Silverman LB, Bhojwani D, Wayne AS. Vincristine Sulfate Liposome Injection With Combination Chemotherapy for Children, Adolescents, and Young Adults With Relapsed Acute Lymphoblastic Leukemia: A Therapeutic Advances in Childhood Leukemia and Lymphoma Consortium Trial. Pediatr Blood Cancer. 2025 May;72(5):e31584. doi: 10.1002/pbc.31584. Epub 2025 Feb 12.

  PMID: 39937083 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Vincristine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Results Point of Contact

• Title: Ellynore Florendo, CCRP
• Organization: Therapeutic Advances in Childhood Leukemia and Lymphoma

eflorendo@chla.usc.edu

323-361-3022

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2016
• First Posted: August 26, 2016
• Study Start: January 31, 2017
• Primary Completion: July 29, 2022
• Study Completion: December 31, 2024
• Last Updated: October 22, 2025
• Results First Posted: October 22, 2025

Record last verified: 2022-07

Locations

US (28); CA (3); AU (4)