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NCT00440726

Bortezomib With Chemotherapy for Relapsed Pediatric Acute Lymphoblastic Leukemia (ALL)

Completed Phase 1, PHASE2 Results posted Last updated 19 February 2020
What this trial tests

Phase 1, PHASE2 trial testing Bortezomib in Acute Lymphoblastic Leukemia in 31 participants. Completed in 26 February 2011.

Timeline
4 August 2006
Primary endpoint
26 February 2011
26 February 2011

Quick facts

Lead sponsorTherapeutic Advances in Childhood Leukemia Consortium
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment31
Start date4 August 2006
Primary completion26 February 2011
Estimated completion26 February 2011
Sites24 locations across Canada, United States, Australia, Brazil

Drugs / interventions tested

Conditions studied

Sponsor

Therapeutic Advances in Childhood Leukemia Consortium

Who can join

Adults 1 to 21, any sex, with Acute Lymphoblastic Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Occurrence of a Dose-Limiting Toxicity (Phase 1) Primary · Beginning with the first dose of investigational product until 30 days following the last dose of bortezomib

Toxicity will be graded using the CTCAE criteria, version 3.0. Dose-limiting toxicity will be defined as any of the following events that are deemed by the investigator as possibly, probably or definitely attributable to bortezomib: Grade 3 or 4 Sensory Neuropathy; Grade 3 or 4 Neuropathic pain (Neuralgia or peripheral nerve) lasting longer than 24 hours despite medical intervention; Marrow hypoplasia, which continues 6 weeks from the start of each course (less than 10% cellularity); and Grade 4 Non-Hematologic Toxicity excluding the following: Infection (septic shock, typhlitis), Fever/Neutro

GroupValue95% CI
Ph 1, Dose Level 1 (1 mg/m2)0
Ph 1, Dose Level 2 (1.3 mg/m2)1
Ph 1, Dose Level 1 (1 mg/m2)4
Ph 1, Dose Level 2 (1.3 mg/m2)5
Achievement of Complete Remission (CR) Primary · Day 29 of Course 1

* Complete Remission (CR): M1 (\< 5% blasts) BM with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (ANC\>750/uL and platelet count \>75 000/uL); * Complete Remission without Platelet Recovery (CRp): M1 BM with no circulating blasts or extramedullary disease and recovery of ANC (\>750/uL) but insufficient recovery of platelets (\<75 000/uL). * Partial Remission (PR): the disappearance of circulating blasts and achievement of M2 (5%-25% blasts) marrow status, without new sites of extramedullary disease, and with recovery of ANC (\>750/uL). * S

GroupValue95% CI
Ph 1 Dose Escalation6
Ph 2 B-Precursor ALL Patients14
Ph 2 T-Cell ALL Patients0
Ph 1 Dose Escalation0
Ph 2 B-Precursor ALL Patients2
Ph 2 T-Cell ALL Patients0
Ph 1 Dose Escalation1
Ph 2 B-Precursor ALL Patients0
Ph 2 T-Cell ALL Patients2
Ph 1 Dose Escalation1
Ph 2 B-Precursor ALL Patients0
Ph 2 T-Cell ALL Patients0
Bone Marrow Response Secondary · Day 29 of Course 1

M1: Less than 5% blasts in a bone marrow aspirate and at least 200 cells counted. M2: 5-25% blasts in a bone marrow aspirate with at least 200 cells counted. M3: Greater than 25% blasts in a bone marrow aspirate with at least 200 cells counted.

GroupValue95% CI
Phase 2 B-Precursor ALL Patients17
Phase 2 T-cell ALL Patients0
Phase 2 B-Precursor ALL Patients0
Phase 2 T-cell ALL Patients2
Phase 2 B-Precursor ALL Patients3
Phase 2 T-cell ALL Patients0

Adverse events — posted to ClinicalTrials.gov

Time frame: 60 days, beginning with the first dose of investigational product until 30 days following the last dose of bortezomib. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

1 mg/m2 Dose Group
Serious: 2/4 (50%)
Deaths: 0/4
1.3 mg/m2 Dose Group
Serious: 17/27 (63%)
Deaths: 5/27

Serious adverse events (37 terms)

ReactionSystem1 mg/m2 Dose Group1.3 mg/m2 Dose Group
Infection w/ Gr 3/4 ANC, BloodInfections and infestations
Neutrophil countInvestigations
Cerebral ischaemiaVascular disorders
Febrile neutropeniaBlood and lymphatic system disorders
Hyperglycemia NOSMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
Hypotension NOSVascular disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Peripheral motor neuropathyNervous system disorders
Peripheral sensory neuropathyNervous system disorders
Platelet count decreasedInvestigations
Activated partial thromboplastin time prolongedInvestigations
Blood bilirubin increasedInvestigations
Bone marrow depression NOSBlood and lymphatic system disorders
CaecitisGastrointestinal disorders
ConfusionPsychiatric disorders
DehydrationMetabolism and nutrition disorders
Depressed level of consciousnessNervous system disorders
Diarrhea NOSGastrointestinal disorders
EncephalopathyNervous system disorders
HypertensionVascular disorders
HypocalcaemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders
Infection w/ Gr 3/4 ANC, BrainInfections and infestations
Other adverse events (77 terms — click to expand)

ReactionSystem1 mg/m2 Dose Group1.3 mg/m2 Dose Group
HypoalbuminemiaMetabolism and nutrition disorders
Leukopenia NOSBlood and lymphatic system disorders
HyponatremiaMetabolism and nutrition disorders
Platelet count decreasedBlood and lymphatic system disorders
HemoglobinBlood and lymphatic system disorders
HypocalcemiaMetabolism and nutrition disorders
Alanine aminotransferase increasedInvestigations
Hyperglycemia NOSMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
HypophosphatemiaMetabolism and nutrition disorders
Neutrophil countBlood and lymphatic system disorders
HypokalaemiaMetabolism and nutrition disorders
HyperkalemiaMetabolism and nutrition disorders
Abdominal pain NOSGastrointestinal disorders
Diarrhea NOSGastrointestinal disorders
Hypoglycemia NOSMetabolism and nutrition disorders
NauseaGastrointestinal disorders
Blood alkaline phosphatase increasedInvestigations
Blood bilirubin increasedInvestigations
HypertensionVascular disorders
Hypotension NOSNervous system disorders
ConstipationGastrointestinal disorders
FatigueGeneral disorders
Pain-OtherGeneral disorders
Prothrombin time prolongedInvestigations
Vomiting NOSGastrointestinal disorders
HypermagnesemiaMetabolism and nutrition disorders
LymphopeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
Blood creatinine increasedInvestigations
Blood fibrinogenInvestigations
Dry skinSkin and subcutaneous tissue disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
HypomagnesemiaMetabolism and nutrition disorders
Activated partial thromboplastin time prolongedInvestigations
AnorexiaMetabolism and nutrition disorders
DizzinessNervous system disorders
HypercalcemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Pain NOSGeneral disorders

Most-reported serious reactions: Infection w/ Gr 3/4 ANC, Blood, Neutrophil count, Cerebral ischaemia, Febrile neutropenia, Hyperglycemia NOS, Hyponatremia, Hypotension NOS, Hypoxia.

Data from ClinicalTrials.gov NCT00440726 adverse events section.

Sponsor's own description

This is a Phase I/II study of a drug called bortezomib given in combination with chemotherapy drugs used to treat acute lymphoblastic leukemia (ALL) that has come back (recurred). Bortezomib is a drug that has been approved by the Food and Drug Administration (FDA) for treating adults with multiple myeloma which is a type of blood cancer. Bortezomib has been shown to cause cancer cells to die in studies done on animals (mice). Studies have been done that have shown that some adults and children with cancer have shown a response to bortezomib when it is used alone. Studies have also been done in adults to evaluate the dose of bortezomib that can be safely given in combination with other chemotherapy drugs.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study.
    Messinger YH, Gaynon PS, Sposto R, van der Giessen J, et al · · 2012 · cited 167× · PMID 22653976 · DOI 10.1182/blood-2012-04-418640
  2. 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.
    Messinger Y, Gaynon P, Raetz E, Hutchinson R, et al · · 2010 · cited 85× · PMID 20582937 · DOI 10.1002/pbc.22456
  3. Advances in paediatric cancer treatment.
    Saletta F, Seng MS, Lau LM. · · 2014 · cited 50× · PMID 26835334 · DOI 10.3978/j.issn.2224-4336.2014.02.01
  4. Cancerous inhibitor of protein phosphatase 2A determines bortezomib-induced apoptosis in leukemia cells.
    Liu CY, Shiau CW, Kuo HY, Huang HP, et al · · 2013 · cited 38× · PMID 22983581 · DOI 10.3324/haematol.2011.050187
  5. Challenges and Opportunities for Childhood Cancer Drug Development.
    Houghton PJ, Kurmasheva RT. · · 2019 · cited 22× · PMID 31558580 · DOI 10.1124/pr.118.016972
  6. Exploiting the reactive oxygen species imbalance in high-risk paediatric acute lymphoblastic leukaemia through auranofin.
    Karsa M, Kosciolek A, Bongers A, Mariana A, et al · · 2021 · cited 17× · PMID 33837299 · DOI 10.1038/s41416-021-01332-x
  7. Molecularly Targeted Small Molecule Inhibitor Therapy for Pediatric Acute Lymphoblastic Leukemia: A Comprehensive Review of Clinical Trials.
    Peccatori N, Brivio E, Lissat A, Bautista Sirvent F, et al · · 2025 · PMID 41154380 · DOI 10.3390/cancers17203322

Verify or expand the search:

Other trials of Bortezomib

Trials testing the same drug.

Other recruiting trials for Acute Lymphoblastic Leukemia

Currently open trials in the same condition.

Other Therapeutic Advances in Childhood Leukemia Consortium trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing