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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02879643




Registration number
NCT02879643
Ethics application status
Date submitted
16/08/2016
Date registered
26/08/2016

Titles & IDs
Public title
Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapsed ALL
Scientific 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
Secondary ID [1] 0 0
T2012-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ALL, Childhood 0 0
Lymphoblastic Leukemia, Acute, Childhood 0 0
Lymphoblastic Leukemia, Acute 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Marqibo

Experimental: Cohort A: Marqibo and UK ALL R3 backbone - * 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.

Experimental: Cohort B: Marqibo and lower intensity UK ALL R3 backbone - * 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.

Experimental: Cohort C: Marqibo and maintenance regimen - * 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


Treatment: Drugs: Marqibo
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Dose Limiting Toxicities as a Measure of Safety and Tolerability
Timepoint [1] 0 0
5 weeks
Secondary outcome [1] 0 0
The response rate after treatment.
Timepoint [1] 0 0
Approx. 8 weeks

Eligibility
Key inclusion 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.
Minimum age
1 Year
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/01/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2022
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [4] 0 0
Royal Children's Hospital, Melbourne - Parkville,
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
3052 - Parkville,
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oregon
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Utah
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
United States of America
State/province [20] 0 0
Wisconsin
Country [21] 0 0
Canada
State/province [21] 0 0
British Columbia
Country [22] 0 0
Canada
State/province [22] 0 0
Ontario
Country [23] 0 0
Canada
State/province [23] 0 0
Montréal, Québec

Funding & Sponsors
Primary sponsor type
Other
Name
Therapeutic Advances in Childhood Leukemia Consortium
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Spectrum Pharmaceuticals, Inc
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ellynore Florendo
Address 0 0
Country 0 0
Phone 0 0
(323) 361- 3022
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02879643