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NCT02419755

Bortezomib and Vorinostat in Younger Patients With Refractory or Relapsed MLL Rearranged Hematologic Malignancies

Terminated Phase 2 Results posted Last updated 7 March 2018
What this trial tests

Phase 2 trial testing Bortezomib in Mixed Lineage Acute Leukemia in 12 participants. Terminated before completion.

Timeline
14 April 2015
Primary endpoint
31 December 2016
31 December 2016

Quick facts

Lead sponsorSt. Jude Children's Research Hospital
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment12
Start date14 April 2015
Primary completion31 December 2016
Estimated completion31 December 2016
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

St. Jude Children's Research Hospital

Who can join

Under 21, any sex, with Mixed Lineage Acute Leukemia or Acute Myeloid 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.

Number of Relevant Toxicities Related to Therapy Secondary · From on-therapy date up to 18 months

Events were graded using CTCAE v. 4.0. All toxicities will be monitored until the completion of therapy (up to 500 days) for patients that do not go on to bone marrow transplant. If a patient goes on to receive a bone marrow transplant, at that point, they will no longer be monitored for toxicity, as any further toxicities may be secondary to the transplant and not the study regimen. This outcome reports those toxicities that are that were possibly, probably or definitely related to therapy. Participants were separately monitored for frequency of grade 5 events, grade 4 sepsis, grade 4 hemorr

Grade 5: death
GroupValue95% CI
Stratum 1: Myeloid Malignancies1
Stratum 2: ALL and MLM3
Grade 4: sepsis
GroupValue95% CI
Stratum 1: Myeloid Malignancies0
Stratum 2: ALL and MLM2
Grade 4: hemorrhage
GroupValue95% CI
Stratum 1: Myeloid Malignancies0
Stratum 2: ALL and MLM1
Grade 4: hepatic toxicity
GroupValue95% CI
Stratum 1: Myeloid Malignancies0
Stratum 2: ALL and MLM0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were recorded from a participant's on-study date until they were taken off study, up to 8 months. Although only 3 Stratum 1 and 4 Stratum 2 participants completed the trial, there were 4 Stratum 1 participants and 6 Stratum 2 participants evaluable for adverse events.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Stratum 1: Myeloid Malignancies
Serious: 1/4 (25%)
Deaths: 4/4
Stratum 2: ALL and MLM
Serious: 2/6 (33%)
Deaths: 6/6

Serious adverse events (6 terms)

ReactionSystemStratum 1: Myeloid Maligna…Stratum 2: ALL and MLM
Adult respiratory distress syndromeRespiratory, thoracic and mediastinal disorders
Heart failureCardiac disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhageRespiratory, thoracic and mediastinal disorders
Lung infectionInfections and infestations
PneumothoraxRespiratory, thoracic and mediastinal disorders
Other adverse events (82 terms — click to expand)

ReactionSystemStratum 1: Myeloid Maligna…Stratum 2: ALL and MLM
HypoxiaRespiratory, thoracic and mediastinal disorders
HyperglycemiaMetabolism and nutrition disorders
HypoalbuminemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders
HyperkalemiaMetabolism and nutrition disorders
HypertensionVascular disorders
Alanine aminotransferase increasedInvestigations
AnemiaBlood and lymphatic system disorders
Aspartate aminotransferase increasedInvestigations
Febrile neutropeniaBlood and lymphatic system disorders
HypertriglyceridemiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
Lymphocyte count decreasedInvestigations
NeuralgiaNervous system disorders
Neutrophil count, decreasedInvestigations
Platelet count, decreasedInvestigations
SepsisInfections and infestations
Upper respiratory infectionInfections and infestations
White blood cell decreasedInvestigations
AnorexiaMetabolism and nutrition disorders
ColitisGastrointestinal disorders
DiarrheaGastrointestinal disorders
FeverGeneral disorders
Fibrinogen, decreasedInvestigations
GGT, increasedInvestigations
HypernatremiaMetabolism and nutrition disorders
HyperuricemiaMetabolism and nutrition disorders
HypoglycemiaMetabolism and nutrition disorders
Lipase increasedInvestigations
Lung InfectionInfections and infestations
Mucosal infectionInfections and infestations
Respiratory failureRespiratory, thoracic and mediastinal disorders
SinusitisInfections and infestations
StridorRespiratory, thoracic and mediastinal disorders
Upper gastrointestinal hemorrhageGastrointestinal disorders
Urinary retentionRenal and urinary disorders
VomitingGastrointestinal disorders
Abdominal painGastrointestinal disorders
AcidosisMetabolism and nutrition disorders

Most-reported serious reactions: Adult respiratory distress syndrome, Heart failure, Hypoxia, Bronchopulmonary hemorrhage, Lung infection, Pneumothorax.

Data from ClinicalTrials.gov NCT02419755 adverse events section.

Sponsor's own description

This study will test the safety and effectiveness of adding bortezomib and vorinostat to other chemotherapy drugs commonly used to treat relapsed or refractory leukemia. Both drugs have been approved by the Food and Drug Administration (FDA) to treat other cancers in adults, but they have not yet been approved tor treatment younger patients with leukemia. PRIMARY OBJECTIVE * To estimate the overall response rate of patients with MLL rearranged (MLLr) hematologic malignancies receiving bortezomib and vorinostat in combination with a chemotherapy backbone. SECONDARY OBJECTIVES * Estimate event-free and overall-survival. * Describe toxicities experienced by participants during treatment. OTHER PRESPECIFIED OBJECTIVES * To identify all genomic lesions by comprehensive whole genome, exome and transcriptome sequencing on all patients. * To compare minimal residual disease (MRD) results by three modalities: flow cytometry, polymerase chain reaction (PCR) and deep sequencing.

Publications & conference data

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

  1. MLL-Rearranged Leukemias-An Update on Science and Clinical Approaches.
    Winters AC, Bernt KM. · · 2017 · cited 289× · PMID 28232907 · DOI 10.3389/fped.2017.00004
  2. The role of the proteasome in AML.
    Csizmar CM, Kim DH, Sachs Z. · · 2016 · cited 47× · PMID 27911437 · DOI 10.1038/bcj.2016.112
  3. Disulfiram overcomes bortezomib and cytarabine resistance in Down-syndrome-associated acute myeloid leukemia cells.
    Bista R, Lee DW, Pepper OB, Azorsa DO, et al · · 2017 · cited 44× · PMID 28143565 · DOI 10.1186/s13046-017-0493-5
  4. The genomics of acute myeloid leukemia in children.
    Conneely SE, Rau RE. · · 2020 · cited 35× · PMID 31925603 · DOI 10.1007/s10555-020-09846-1
  5. The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia.
    Janczar S, Janczar K, Pastorczak A, Harb H, et al · · 2017 · cited 28× · PMID 28054944 · DOI 10.3390/cancers9010002
  6. Genetic and Epigenetic Targeting Therapy for Pediatric Acute Lymphoblastic Leukemia.
    Xu H, Yu H, Jin R, Wu X, et al · · 2021 · cited 16× · PMID 34943855 · DOI 10.3390/cells10123349
  7. Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia.
    Yin L, Wan L, Zhang Y, Hua S, et al · · 2024 · cited 10× · PMID 39428967 · DOI 10.1002/cam4.70326
  8. Acute Myeloid Leukemia: Advancements in Diagnosis and Treatment.
    Yu MG, Zheng HY. · · 2017 · cited 8× · PMID 28091414 · DOI 10.4103/0366-6999.198004

Verify or expand the search:

Other trials of Bortezomib

Trials testing the same drug.

Other recruiting trials for Mixed Lineage Acute Leukemia

Currently open trials in the same condition.

Other St. Jude Children's Research Hospital trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02419755.

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