Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01483690




Trial ID
NCT01483690
Ethics application status
Date submitted
29/11/2011
Date registered
30/11/2011
Date last updated
20/11/2015

Titles & IDs
Public title
A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL
Scientific title
A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL
Secondary ID [1] 0 0
T2009-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukemia 0 0
Precursor B-Cell Lymphoblastic Leukemia 0 0
Precursor T-Cell Lymphoblastic Leukemia 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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Decitabine
Treatment: Drugs - Vorinostat
Treatment: Drugs - Vincristine
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Mitoxantrone
Treatment: Drugs - Pegaspargase
Treatment: Drugs - Methotrexate

Treatment: Drugs: Decitabine
10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19.

Treatment: Drugs: Vorinostat
180 mg/m2/day (Max dose=400mg daily) given orally on days 2 through 7 and days 16 through 21.

Treatment: Drugs: Vincristine
1.5 mg/m2/day (Max dose 2 mg) given IV push on days 10, 17, 24 and 31.

Treatment: Drugs: Dexamethasone
20 mg/m2/day divided BID given orally on days 8 through 12 and 22 through 26.

Treatment: Drugs: Mitoxantrone
10 mg/m2/day given on days 8 and 9 as a short IV infusion over 5-15 minutes; do not infuse over less than 3 minutes

Treatment: Drugs: Pegaspargase
2500 international units/m2/day IM or IV on days 10 and 24.

Treatment: Drugs: Methotrexate
Given intrathecally to all patients the dose defined by age below.
8 mg for patients age 1-1.99
10 mg for patients age 2-2.99
12 mg for patients 3-8.99 years of age
15 mg for patients >9 years of age
CNS 1 or 2 patients get doses on day 8, 22 and 35 and CNS 3 patients should get doses on day 8, 15, 22, 29 and 35

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

Outcomes
Primary outcome [1] 0 0
Number of participants with adverse events. - To evaluate the side effects of giving decitabine and vorinostat before and during chemotherapy using the standard drugs vincristine, dexamethasone, PEG-asparaginase and mitoxantrone.
Timepoint [1] 0 0
6 weeks
Secondary outcome [1] 0 0
Disease response rate after treatment. - The study will assess whether the patient's acute lymphoblastic leukemia goes into remission after treatment.
Timepoint [1] 0 0
6 weeks
Secondary outcome [2] 0 0
Gene-specific methylation profiles - To assess the biologic activity of decitabine by comparing pre and post-treatment marrow samples for global and gene-specific methylation profiles using HELP and methylation-specific PCR.
Timepoint [2] 0 0
2 years
Secondary outcome [3] 0 0
Global histone acetylation and histone modifications - To assess the biological activity of vorinostat by comparing pre- and post-treatment blood and bone marrow samples for global histone acetylation (using acetyl-H3 Western blotting), and for gene-specific histone modifications (using H3K9/14Ac ChIP-chip and ChIP-qPCR).
Timepoint [3] 0 0
2 years
Secondary outcome [4] 0 0
Gene expression profiles - To determine the impact of combined epigenetic therapy on the expression of epigenetically-regulated genes by comparing pre and post-treatment marrow samples for gene expression profiles (using microarrays), and correlating these with the methylation and histone modification assays.
Timepoint [4] 0 0
2 years

Eligibility
Key inclusion criteria
- Patients must be =1 and = 21 years of age when originally diagnosed with ALL.

Diagnosis

- Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) with = 25% blasts
in the bone marrow (M3), with or without extramedullary disease.

- Patients may have CNS 1, 2 or 3 disease.

- Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients = 16
years of age.

- Prior Therapy

- Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

- Patients must have had 2 or more prior therapeutic attempts defined as:

- Relapse after going into remission from re-induction for the first or subsequent
relapse (ie: 2nd , 3rd, 4th…relapse), OR

- Refractory disease after first or greater relapse and a re-induction attempt, OR

- Failing to go into remission from original diagnosis after 2 previous induction
attempts.

- Hematopoietic Stem Cell Transplant: Patients who have experienced their relapse after
a HSCT are eligible, provided they have no evidence of Graft-versus-Host Disease
(GVHD) and are at least 60 days post-transplant at the time of enrollment.

- Prior anthracycline exposure: Patients must have less than 400 mg/m2 lifetime exposure
of anthracycline chemotherapy. (See Appendix II for calculation worksheet)

- Hematopoietic grow factors: It must have been at least 7 days since the completion of
therapy with 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) therapy: It must be at least 7 days after last does of
biologic agent. For agents that have known adverse events occurring beyond 7 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

- Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after
the last dose of monoclonal antibody. (ie. Rituximab=66 days, Epratuzumab=69 days)

- Immunotherapy: At least 42 days after the completion of any type of immunotherapy,
e.g. tumor vaccines.

Renal and Hepatic 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 GRF =
70mL/min/1.73m2.

- Patient's ALT and AST must be < 5 x institutional upper limit of norm ULN. The hepatic
requirements are waived for patients with known or suspected liver involvement who
would otherwise be eligible after consultation with the Study Chair or Vice Chair.

- Patient's total bilirubin must be = 1.5 x ULN. The hepatic requirements are waived for
patients with known or suspected liver involvement who would otherwise be eligible.

Cardiac Function:

- Patient must have a shortening fraction = 27% by Echo or an ejection fraction = 50% by
MUGA.

Reproductive Function

- Female patients of childbearing potential must have a negative urine or serum
pregnancy test confirmed prior to enrollment.

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

- Male and female patients of child-bearing potential must agree to use an effective
method of contraception approved by the investigator during the study.
Minimum age
1 Year
Maximum age
21 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients will be excluded if they are receiving Valproic Acid (VPA) therapy.

- Patients will be excluded if they have a known allergy to any of the drugs used in the
study.

- Patients will be excluded if they have a systemic fungal, bacterial, viral or other
infection that is exhibiting ongoing signs/symptoms related to the infection without
improvement despite appropriate antibiotics or other treatment.

- Patients will be excluded if there is a plan to administer non-protocol chemotherapy,
radiation therapy, or immunotherapy during the study period.

- Patients will be excluded if they have significant concurrent disease, illness,
psychiatric disorder or social issue that would compromise patient safety or
compliance with the protocol treatment or procedures, interfere with consent, study
participation, follow up, or interpretation of study results.

- Patients will be excluded if they have had any positive fungal culture in the last 30
days prior to enrollment.

Study design
Purpose of the study
Treatment
Allocation to intervention
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
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Royal Children's Hospital - Brisbane
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Sydney
Recruitment hospital [3] 0 0
Children's Hospital at Westmead - Westmead, NSW
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
- Sydney
Recruitment postcode(s) [3] 0 0
- Westmead, NSW
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
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Other
Name
Therapeutic Advances in Childhood Leukemia Consortium
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a pilot study using decitabine and vorinostat before and during chemotherapy with
vincristine, dexamethasone, mitoxantrone, and peg-asparaginase in pediatric patients with
acute lymphoblastic leukemia (ALL).
Trial website
https://clinicaltrials.gov/show/NCT01483690
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Burke, MD
Address 0 0
Medical College of Wisconsin
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries