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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00440726




Registration number
NCT00440726
Ethics application status
Date submitted
23/02/2007
Date registered
27/02/2007

Titles & IDs
Public title
Bortezomib With Chemotherapy for Relapsed Pediatric Acute Lymphoblastic Leukemia (ALL)
Scientific title
A Study of Bortezomib With Chemotherapy for Relapsed/Refractory Acute Lymphoblastic Leukemia
Secondary ID [1] 0 0
T2005-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute 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 - Bortezomib
Treatment: Drugs - Dexamethasone
Treatment: Drugs - PEG-asparaginase
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Cytarabine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Vincristine
Treatment: Drugs - Triple IT Therapy

Experimental: Ph 1 Dose Escalation - Intervention: Bortezomib with chemotherapy (dexamethasone, PEG-asparaginase, doxorubicin, cytarabine, methotrexate, and vincristine) and Triple IT therapy for patients who are CNS 2 or 3 at study entry. 3+3 escalation design.

Experimental: Ph 2 Efficacy and Safety - Intervention: Bortezomib with chemotherapy (dexamethasone, PEG-asparaginase, doxorubicin, cytarabine, methotrexate, and vincristine) and Triple IT therapy for patients who are CNS 2 or 3 at study entry. Patients receive bortezomib at maximum tolerated dose (as established in the Phase 1 portion of the study) and are assessed for response and toxicity.


Treatment: Drugs: Bortezomib
Intravenous on days 1, 4, 8 and 11. Dose assigned at study entry.

Treatment: Drugs: Dexamethasone
10 mg/m2/day divided BID, oral administration for 14 days.

Treatment: Drugs: PEG-asparaginase
2500 IU/m2/day, intramuscular injection on Days 2, 8, 15 and 22

Treatment: Drugs: Doxorubicin
60 mg/m2/day IV over 15 minutes on Day 1

Treatment: Drugs: Cytarabine
Given intrathecally on Day 1 of course 1 at the dose defined by age below.

* 30 mg for patients age 1-1.99
* 50 mg for patients age 2-2.99
* 70 mg for patients \>3 years of age

Treatment: Drugs: Methotrexate
Given intrathecally to all patients who are CNS 1 at study entry on Day 15 at 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

Treatment: Drugs: Vincristine
1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22.

Treatment: Drugs: Triple IT Therapy
Triple IT therapy will be given intrathecally on Day 8, 15, and 22 for patients who are CNS 2 and CNS 3 at study entry. Regimen/dosing as follows:

Methotrexate-

* \<2 years: 8 mg
* 2 - \<3 y: 10 mg
* 3 - \<9 y: 12 mg
* \>=9 y: 15 mg

Cytarabine:

* \<2 years: 16 mg
* 2 - \<3 y: 20 mg
* 3 - \<9 y: 24 mg
* \>=9 y: 30 mg

Hydrocortisone:

* \<2 years: 8 mg
* 2 - \<3 y: 10 mg
* 3 - \<9 y: 12 mg
* \>=9 y: 15 mg
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of a Dose-Limiting Toxicity (Phase 1)
Timepoint [1] 0 0
Beginning with the first dose of investigational product until 30 days following the last dose of bortezomib
Primary outcome [2] 0 0
Achievement of Complete Remission (CR)
Timepoint [2] 0 0
Day 29 of Course 1

Eligibility
Key inclusion criteria
Inclusion Criteria

The eligibility criteria listed below are interpreted literally and cannot be waived.

1. Age Patients must be < 21 years of age when originally diagnosed with ALL. Patient must be > 1 year of age at study entry.
2. Diagnosis Patients must have relapsed or refractory ALL with a M3 marrow (marrow blasts >25%). Patients with CNS I, II or III or testicular disease are eligible.
3. Performance Level Karnofsky > 50% for patients > 10 years of age and Lansky > 50% for patients < 10 years of age.
4. Prior Therapy Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

1. Prior anthracycline exposure: Patients must have less than 400mg/m2 lifetime exposure of anthracycline chemotherapy.
2. Stem Cell Transplant (SCT): Patients are eligible after allogeneic stem cell transplant as long as patients are not actively being treated for graft-versus-host-disease (GvHD).
3. Patients should not have received previous therapy using bortezomib (Velcdade® or PS-341).
4. During the phase I portion of the trial, there is no limit on the number of prior treatment regimens. Patients with persistent disease after an induction attempt are eligible.
5. During the phase II portion of the trial, patients must have had two or more prior therapeutic attempts defined as:

* Persistent initial disease after two induction attempts, or
* Relapse after one-reinduction attempt (2nd relapse), or
* Persistent disease after first relapse and initial re-induction attempt

(Patients in first relapse are not eligible for the phase II portion of the study)
6. During the phase II portion of the trial, patients must have no more than 3 prior therapeutic attempts and it must be at least 3 months since the last treatment with a "VPLD" induction/re-induction regimen.
5. Reproductive Function

1. Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.
2. Female patients with infants must agree not to breastfeed their infants while on this study.
3. 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
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

1. Drug Allergies

Patients will be excluded if they have allergies to the following:
* Asparaginase products
* Boron
* Mannitol
2. Renal Function Patients will be excluded if their serum creatinine is > 2 x the upper limit of normal for age at the institution's laboratory.
3. Liver/Pancreatic Function

1. Direct bilirubin > 1.5x the institutional ULN for age. A total bilirubin result that is less than 1.5 times the institutional ULN for age may be used for eligibility if a direct bilirubin result is not available.
2. SGPT (ALT) > 4 x institutional ULN
3. Grade 3 or greater pancreatitis as defined by the CTCAE v3.0
4. History of any L-asparaginase induced pancreatitis
5. Amylase or Lipase > 2 x institutional ULN
4. Cardiac Function Patients will be excluded if their shortening fraction by echocardiogram is less than 30%.
5. Patients with Down Syndrome are excluded.
6. Infection

* Patients will be excluded if they have an active uncontrolled infection.
* Patients will be excluded if they have had a positive culture within 2 weeks of study entry.
7. Patients with grade 2 or greater motor or sensory neuropathy per CTC 3.0 criteria.
8. Patients planning on receiving other investigational agents while on this study. (An investigational agent is defined as any drug not currently approved for use in humans.)
9. Patients planning on receiving other anti-cancer therapies while on this study. Hydroxyurea for cyto-reduction is allowed prior to the start of therapy.
10. Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
11. Patients who have started protocol therapy prior to enrollment. Patient may still enroll if IT therapy was given within 72 hours of study enrollment as part of the diagnostic lumbar procedure.

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

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/08/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/02/2011
Sample size
Target
Accrual to date
Final
31
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
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
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Brazil
State/province [15] 0 0
São Paulo
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario

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

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Yoav Messinger, MD
Address 0 0
Children's Hospital and Clinics of Minnesota
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

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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents



Results are available at https://clinicaltrials.gov/study/NCT00440726