Clinical Trials /

Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapsed ALL

NCT02879643

Description:

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).

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Lymphoblastic Lymphoma
  • Mixed Phenotype Acute Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapsed ALL
  • Official Title: A Pilot Study of Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapse of Acute Lymphoblastic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: T2012-002
  • NCT ID: NCT02879643

Conditions

  • ALL, Childhood
  • Lymphoblastic Leukemia, Acute, Childhood
  • Lymphoblastic Leukemia, Acute

Interventions

DrugSynonymsArms
MarqiboCohort A: Marqibo and UK ALL R3 backbone

Purpose

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).

Detailed Description

      This study will utilize Marqibo® as a replacement for standard vincristine in combination
      with chemotherapy for children with relapsed ALL. The hypothesis is that the incorporation of
      Marqibo® with combination chemotherapy will be safe and feasible. In the context of this
      pilot study, overall outcomes and efficacy will be a secondary objective. It is hypothesized
      that data from this combination may show improved efficacy including, complete remission
      (CR), minimal residual disease (MRD) negativity, and progression free survival (PFS) rates
      and safety (i.e., neurotoxicity) in comparison to outcomes in historical regimens, including
      the UK ALL R3 with standard vincristine.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort A: Marqibo and UK ALL R3 backboneExperimentalMarqibo®: 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.
  • Marqibo
Cohort B: Marqibo and lower intensity UK ALL R3 backboneExperimentalMarqibo®: 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.
  • Marqibo
Cohort C: Marqibo and maintenance regimenExperimentalMarqibo®: 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
  • Marqibo

Eligibility Criteria

        Inclusion Criteria

        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.

               1. 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).

               2. 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®).

          -  Biologic anti-neoplastic agents: At least seven days after the last dose of a biologic
             agent. For agents that have known adverse events occurring beyond seven days after
             administration, this period must be extended beyond the time during which adverse
             events are known to occur. The duration of this interval must be discussed with the
             study chair or vice chair.

          -  Monoclonal antibodies: At least three half-lives (or 30 days—whichever is longer) of
             the antibody must have elapsed after the last dose of monoclonal antibody. (e.g.,
             Rituximab = 66 days, Epratuzumab = 69 days)

          -  Immunotherapy: At least 30 days after the completion of any type of immunotherapy,
             e.g. tumor vaccines, chimeric antigen receptor T-cells.

          -  Recent prior chemotherapy: At least 10 days after standard vincristine and the
             completion of any type of chemotherapy induction regimen. At least 3 weeks after
             radiation therapy. At least 30 days after the completion of any investigational
             neoplastic agent is also required. An investigational agent is defined as any drug
             that is not approved and licensed for sale by the FDA for institutions in the United
             States, by Health Canada for institutions in Canada and by The Therapeutic Goods
             Administration for institutions in Australia.

        Exceptions:

          -  There is no time restriction in regard to prior intrathecal chemotherapy provided
             there is complete recovery from any acute toxic effects of such; it is allowable to
             enroll a patient that has received IT Cytarabine (ARA-C), IT Methotrexate (MTX) or
             triple IT therapy within 14 days of enrollment as part of their evaluation to diagnose
             disease relapse. The IT therapy given within 14 days of initiation of protocol
             specified chemotherapy, may substitute for the day 1 IT in cohorts A and B

          -  Subjects with rapidly progressive disease may receive hydroxyurea until they begin
             study therapy;

          -  Patients who relapse while on maintenance-type ALL therapy or are receiving
             maintenance therapy for disease stabilization will not require a wash-out period
             before entry into this study. However, there must be at least 10 days after any dose
             of standard vincristine.

        Renal and Hepatic Function

          -  Renal function: Patient's serum creatinine must be ≤ 1.5 x institutional upper limit
             of normal (ULN) according to age. If the serum creatinine is greater than 1.5 times
             normal, the patient must have a calculated creatinine clearance or radioisotope
             glomerular filtration rate (GFR) ≥ 70milliliter/min/1.73m2. Alternatively, a 24-hour
             creatinine clearance may also be used.

          -  Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
             must be < 5 x institutional upper limit of norm ULN. Total bilirubin must be ≤ 1.5 x
             ULN (except in the case of subjects with documented Gilbert's disease ≤ 5 × ULN).

        Cardiac Function

        -Patients must have a shortening fraction ≥ 27% or an ejection fraction ≥ 55% by
        echocardiogram, cardiac MRI or multigated acquisition scan (MUGA).

        Reproductive Function

          -  Female patients must not be pregnant and those of childbearing potential must have a
             negative urine or serum pregnancy test confirmed within one week prior to enrollment.

          -  Female patients with infants must agree not to breastfeed their infants while on this
             study.

          -  Male and female patients of childbearing potential must agree to use an effective
             method of contraception during the study.

        Exclusion Criteria

        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).
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Dose Limiting Toxicities as a Measure of Safety and Tolerability
Time Frame:5 weeks
Safety Issue:
Description:The incidence of dose limiting toxicity (DLT) will be measured at different dose levels.

Secondary Outcome Measures

Measure:The response rate after treatment.
Time Frame:Approx. 8 weeks
Safety Issue:
Description:The rate of remission will be assessed after 1 courses of therapy. A bone marrow aspirate/biopsy and CBC will be conducted to assess response.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Therapeutic Advances in Childhood Leukemia Consortium

Last Updated

February 11, 2019