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NCT02716805

Phase 1 Study of Tremelimumab, Durvalumab, High-dose Chemotherapy, + Autologous Stem Cell Transplant

Terminated Phase 1 Results posted Last updated 12 October 2022
What this trial tests

Phase 1 trial testing Tremelimumab in Multiple Myeloma in 6 participants. Terminated before completion.

Timeline
13 December 2016
Primary endpoint
16 February 2018
16 February 2018

Quick facts

Lead sponsorLudwig Institute for Cancer Research
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment6
Start date13 December 2016
Primary completion16 February 2018
Estimated completion16 February 2018
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Ludwig Institute for Cancer Research

Who can join

18 and older, any sex, with Multiple Myeloma. 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 Subjects With Treatment-emergent Adverse Events Primary · up to 14 months

Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from the time of enrollment through the end of the study period. DLTs were assessed from the first dose of study drug through the Cycle 2 administration of tremelimumab ± durvalumab post ASCT. DLTs were defined per protocol as lack of neutrophil/platelet engraftment by Day 30 post ASCT; Grade 5 toxicity (treatment-related

Any TEAE
GroupValue95% CI
Cohort 16
Maximum grade 2 TEAE
GroupValue95% CI
Cohort 12
Maximum grade 4 TEAE
GroupValue95% CI
Cohort 14
Immune-related TEAE
GroupValue95% CI
Cohort 11
Tremelimumab-related TEAE
GroupValue95% CI
Cohort 15
Durvalumab-related TEAE
GroupValue95% CI
Cohort 11
Serious TEAE
GroupValue95% CI
Cohort 11
TEAE Leading to Treatment Discontinuation
GroupValue95% CI
Cohort 10
Number of Subjects With Best Response According to International Myeloma Working Group (IMWG) Consensus Criteria Secondary · Up to 14 months

Response was evaluated by appropriate imaging and myeloma serum/urine tests at the start of Cycle 1 and end of study, with response categorized per IMWG consensus criteria, as follows: stringent complete response (sCR) - CR criteria + normal free light chain (FLC) ratio + no clonal cells in bone marrow; CR - negative immunofixation on serum/urine + no soft tissue plasmacytomas + \<5% plasma cells in bone marrow; very good partial response (VGPR) - serum/urine M-protein detectable by immunofixation but not electrophoresis OR ≥90% reduction in serum M-protein + urine \<100 mg/24h; PR - ≥50% and

sCR
GroupValue95% CI
Cohort 11
VGPR
GroupValue95% CI
Cohort 12
Progressive disease
GroupValue95% CI
Cohort 11

Adverse events — posted to ClinicalTrials.gov

Time frame: All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs). The AE reporting period for this study was up to 14 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1
Serious: 1/6 (17%)
Deaths: 0/6

Serious adverse events (2 terms)

ReactionSystemCohort 1
Acute kidney injuryRenal and urinary disorders
HypercalcaemiaMetabolism and nutrition disorders
Other adverse events (45 terms — click to expand)

ReactionSystemCohort 1
NauseaGastrointestinal disorders
Weight decreasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
LeukopeniaBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders
ConstipationGastrointestinal disorders
PancreatitisGastrointestinal disorders
Blood blisterSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
Influenza like illnessGeneral disorders
OedemaGeneral disorders
Oedema peripheralGeneral disorders
Peripheral swellingGeneral disorders
Amylase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Blood creatinine increasedInvestigations
Thyroxine decreasedInvestigations
DizzinessNervous system disorders
DysgeusiaNervous system disorders
HeadacheNervous system disorders
Jugular vein occlusionNervous system disorders
Memory impairmentNervous system disorders
Neuropathy peripheralNervous system disorders
Dyspnoea exertionalRespiratory, thoracic and mediastinal disorders
Throat irritationRespiratory, thoracic and mediastinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Sinus tachycardiaCardiac disorders
TachycardiaCardiac disorders
DiverticulitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Back painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Acute kidney injury, Hypercalcaemia.

Data from ClinicalTrials.gov NCT02716805 adverse events section.

Sponsor's own description

This was a Phase 1, open-label, multicenter, study of checkpoint inhibitor therapy (tremelimumab ± durvalumab) prior to and following autologous stem cell transplant (ASCT) and high-dose melphalan in subjects with multiple myeloma who were at a high risk for relapse, were eligible for ASCT, and had available cryopreserved stem cells. Primary study objectives were to determine the safety and tolerability of study treatment. Further objectives were to evaluate the clinical efficacy and biologic activity of the regimen.

Publications & conference data

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

  1. Checkpoint inhibitors in hematological malignancies.
    Ok CY, Young KH. · · 2017 · cited 93× · PMID 28482851 · DOI 10.1186/s13045-017-0474-3
  2. Immune Regulatory Processes of the Tumor Microenvironment under Malignant Conditions.
    Pansy K, Uhl B, Krstic J, Szmyra M, et al · · 2021 · cited 87× · PMID 34948104 · DOI 10.3390/ijms222413311
  3. Update on PD-1/PD-L1 Inhibitors in Multiple Myeloma.
    Jelinek T, Paiva B, Hajek R. · · 2018 · cited 82× · PMID 30505301 · DOI 10.3389/fimmu.2018.02431
  4. Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway.
    Tremblay-LeMay R, Rastgoo N, Chang H. · · 2018 · cited 53× · PMID 29580288 · DOI 10.1186/s13045-018-0589-1
  5. Immune checkpoint blockade for hematologic malignancies: a review.
    Pianko MJ, Liu Y, Bagchi S, Lesokhin AM. · · 2017 · cited 48× · PMID 28529947 · DOI 10.21037/sci.2017.03.04
  6. Monoclonal Antibodies for the Treatment of Multiple Myeloma: An Update.
    Abramson HN. · · 2018 · cited 42× · PMID 30544512 · DOI 10.3390/ijms19123924
  7. Monoclonal Antibody Therapies for Hematological Malignancies: Not Just Lineage-Specific Targets.
    Cuesta-Mateos C, Alcaraz-Serna A, Somovilla-Crespo B, Muñoz-Calleja C. · · 2017 · cited 39× · PMID 29387053 · DOI 10.3389/fimmu.2017.01936
  8. Targeting the programmed death-1 pathway in lymphoid neoplasms.
    Ok CY, Young KH. · · 2017 · cited 32× · PMID 28242522 · DOI 10.1016/j.ctrv.2017.01.009

Verify or expand the search:

Other trials of Tremelimumab

Trials testing the same drug.

Other recruiting trials for Multiple Myeloma

Currently open trials in the same condition.

Other Ludwig Institute for Cancer Research trials

Trials by the same sponsor.

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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/NCT02716805.

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