Bortezomib With Chemotherapy for Relapsed Pediatric Acute Lymphoblastic Leukemia (ALL)
NCT ID: NCT00440726
Last Updated: 2020-02-19
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1/PHASE2
31 participants
INTERVENTIONAL
2006-08-04
2011-02-26
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Four Drug Reinduction With Bortezomib for Relapsed or Refractory ALL or LL in Children and Young Adults
NCT02535806
Bortezomib, Mitoxantrone, Etoposide, and Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia
NCT01127009
Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia
NCT00666588
Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
NCT00742625
Phase I Combination of Midostaurin, Bortezomib, and Chemo in Relapsed/Refractory Acute Myeloid Leukemia
NCT01174888
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Treatment on this study will consist of a combination of 7 anti-cancer medications. The 7 anti-cancer medicines are bortezomib, vincristine, dexamethasone, PEG-asparaginase, doxorubicin, cytarabine (Ara-C), and methotrexate (MTX).
If you are in the Phase I portion of this study, you will be given an assigned dose of bortezomib. The dose of bortezomib will be based on doses given in previous studies done with adults and children. At each dose level of bortezomib, between 3 and 6 children will receive bortezomib in combination with chemotherapy. If the side effects are not too severe, the next group of children will receive a higher dose. The dose will continue to be increased until we find the dose that causes serious side effects. Your dose of bortezomib will not be increased. If you have bad side effects, your dose may be decreased.
The dose used during the Phase 2 part of this study will be determined by the outcome of the Phase I study. The highest dose used in Phase I that was tolerated without serious side effects will be the one used in Phase 2.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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.
Bortezomib
Intravenous on days 1, 4, 8 and 11. Dose assigned at study entry.
Dexamethasone
10 mg/m2/day divided BID, oral administration for 14 days.
PEG-asparaginase
2500 IU/m2/day, intramuscular injection on Days 2, 8, 15 and 22
Doxorubicin
60 mg/m2/day IV over 15 minutes on Day 1
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
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
Vincristine
1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22.
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
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.
Bortezomib
Intravenous on days 1, 4, 8 and 11. Dose assigned at study entry.
Dexamethasone
10 mg/m2/day divided BID, oral administration for 14 days.
PEG-asparaginase
2500 IU/m2/day, intramuscular injection on Days 2, 8, 15 and 22
Doxorubicin
60 mg/m2/day IV over 15 minutes on Day 1
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
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
Vincristine
1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22.
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
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Bortezomib
Intravenous on days 1, 4, 8 and 11. Dose assigned at study entry.
Dexamethasone
10 mg/m2/day divided BID, oral administration for 14 days.
PEG-asparaginase
2500 IU/m2/day, intramuscular injection on Days 2, 8, 15 and 22
Doxorubicin
60 mg/m2/day IV over 15 minutes on Day 1
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
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
Vincristine
1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22.
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
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
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.
Exclusion Criteria
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.
1 Year
21 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Therapeutic Advances in Childhood Leukemia Consortium
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Yoav Messinger, MD
Role: STUDY_CHAIR
Children's Hospital and Clinics of Minnesota
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
City of Hope
Duarte, California, United States
Miller Children's Hospital
Long Beach, California, United States
Childrens Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital & Research Center Oakland
Oakland, California, United States
Stanford University Medical Center
Palo Alto, California, United States
UCSF School of Medicine
San Francisco, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
University of Miami Cancer Center
Miami, Florida, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Johns Hopkins / Sydney Kimmel Cancer Center
Baltimore, Maryland, United States
Dana Farber Cancer Center
Boston, Massachusetts, United States
C.S. Mott Children's Hospital
Ann Arbor, Michigan, United States
Childrens Hospital & Clinics of Minnesota
Minneapolis, Minnesota, United States
New York University Medical Center
New York, New York, United States
Children's Hospital New York-Presbyterian
New York, New York, United States
Levine Children's Hospital
Charlotte, North Carolina, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Primary Children's Hospital
Salt Lake City, Utah, United States
Seattle Children's Hospital
Seattle, Washington, United States
Sydney Children's Hospital
Randwick, New South Wales, Australia
The Children's Hospital at Westmead
Westmead, New South Wales, Australia
Universidade Federale de Sao Paulo/Hospital Sao Paulo
São Paulo, , Brazil
Sick Kids
Toronto, Ontario, Canada
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Messinger Y, Gaynon P, Raetz E, Hutchinson R, Dubois S, Glade-Bender J, Sposto R, van der Giessen J, Eckroth E, Bostrom BC. Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia (ALL): a report from the therapeutic advances in childhood leukemia (TACL) consortium. Pediatr Blood Cancer. 2010 Aug;55(2):254-9. doi: 10.1002/pbc.22456.
Messinger YH, Gaynon PS, Sposto R, van der Giessen J, Eckroth E, Malvar J, Bostrom BC; Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Consortium. Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study. Blood. 2012 Jul 12;120(2):285-90. doi: 10.1182/blood-2012-04-418640. Epub 2012 May 31.
Related Links
Access external resources that provide additional context or updates about the study.
Click here for more information about this protocol and the Therapeutic Advances in Childhood Leukemia Consortium
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
T2005-003
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.