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NCT03121534

Ibrutinib, Nivolumab and Blinatumomab in Richter Transformation

Terminated Phase 2 Results posted Last updated 17 February 2023
What this trial tests

Phase 2 trial testing Blinatumomab in Hematopoietic/Lymphoid Cancer in 9 participants. Terminated before completion.

Timeline
22 June 2017
Primary endpoint
11 February 2022
11 February 2022

Quick facts

Lead sponsorM.D. Anderson Cancer Center
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment9
Start date22 June 2017
Primary completion11 February 2022
Estimated completion11 February 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

M.D. Anderson Cancer Center — full company profile →

Who can join

18 and older, any sex, with Hematopoietic/Lymphoid Cancer or Richter's Transformation. 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 Participants With a Response Primary · 2 months

Response is defined as complete remission (CR) plus partial remission (PR). Complete Remission (CR) is Lymph nodes None \>/= 1.5 cm, Spleen size \< 13 cm; normal liver size, the absence of constitutional symptoms, normal circulating lymphocyte count, platelets \>/= 100 x 10\^9/L, Hemoglobin \>/= 11.0 g/dL (absence of transfusion and without erythropoietin) and marrow normocellular, no CLL cells and no B-lymphoid nodules. Partial Remission (PR) is any two of the following must decrease \>/= 50% from baseline: lymph nodes, Liver and/or spleen size, circulating lymphocyte count in addition to one

GroupValue95% CI
Ibrutinib, Nivolumab and Blinatumomab2
Number of Participants to Achieve Complete Remission Secondary · Up to 4 years, 8 months

Complete Remission is defined as: Complete Remission (CR) is Lymph nodes None \>/= 1.5 cm, Spleen size \< 13 cm; normal liver size, the absence of constitutional symptoms, normal circulating lymphocyte count, platelets \>/= 100 x 10\^9/L, Hemoglobin \>/= 11.0 g/dL (absence of transfusion and without erythropoietin) and marrow normocellular, no CLL cells and no B-lymphoid nodules.

GroupValue95% CI
Ibrutinib, Nivolumab and Blinatumomab1
Progression Free Survival Secondary · Up to 4 years, 8 months

Time from date of treatment start until the date of first objective documentation of disease-relapse.

GroupValue95% CI
Ibrutinib, Nivolumab and Blinatumomab1.91 – 17
Overall Survival Secondary · Up to 4 years, 8 Months

Time from date of treatment start until date of death due to any cause or last Follow-up.

GroupValue95% CI
Ibrutinib, Nivolumab and Blinatumomab10.35 – 48

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 4 years, 8 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ibrutinib, Nivolumab and Blinatumomab
Serious: 9/9 (100%)
Deaths: 0/9

Serious adverse events (12 terms)

ReactionSystemIbrutinib, Nivolumab and B…
Lung InfectionInfections and infestations
HypercalcemiaMetabolism and nutrition disorders
Cytokine Release SyndromeImmune system disorders
FractureInjury, poisoning and procedural complications
Nervous System DisorderNervous system disorders
Creatinine IncreasedInvestigations
ChillsGeneral disorders
FatigueGeneral disorders
HypotensionVascular disorders
Metabolism and nutrition disorders - Other, specifyMetabolism and nutrition disorders
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specifyNeoplasms benign, malignant and unspecified (incl cysts and polyps)
FeverGeneral disorders
Other adverse events (55 terms — click to expand)

ReactionSystemIbrutinib, Nivolumab and B…
FeverGeneral disorders
FatigueGeneral disorders
Alkaline phosphatase increasedInvestigations
HypercalcemiaMetabolism and nutrition disorders
InvestigationsInvestigations
Lung infectionInfections and infestations
TremorNervous system disorders
Alanine aminotransferase increasedInvestigations
ConfusionPsychiatric disorders
Creatinine increasedInvestigations
Cytokine release syndromeImmune system disorders
EdemaGeneral disorders
General disorders and administration site conditionsGeneral disorders
HypertensionVascular disorders
HypoalbuminemiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
Sinus tachycardiaCardiac disorders
Abdominal distensionGastrointestinal disorders
Allergic rhinitisRespiratory, thoracic and mediastinal disorders
AnorexiaGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Aspartate aminotransferase increasedInvestigations
Atrial fibrillationCardiac disorders
Blood bilirubin increasedInvestigations
BruisingSkin and subcutaneous tissue disorders
ChillsGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
DysgeusiaNervous system disorders
DysphasiaNervous system disorders
Erectile dysfunctionReproductive system and breast disorders
FallInjury, poisoning and procedural complications
Gastrointestinal disordersGastrointestinal disorders
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
Hearing impairedEar and labyrinth disorders
HyperkalemiaMetabolism and nutrition disorders
HypermagnesemiaMetabolism and nutrition disorders
HyperuricemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders

Most-reported serious reactions: Lung Infection, Hypercalcemia, Cytokine Release Syndrome, Fracture, Nervous System Disorder, Creatinine Increased, Chills, Fatigue.

Data from ClinicalTrials.gov NCT03121534 adverse events section.

Sponsor's own description

The goal of this clinical research study is to learn if blinatumomab can help to control Richter Transformation (RT, a type of blood cancer). The safety of this drug will also be studied. This is an investigational study. Blinatumomab is FDA approved and commercially available for the treatment of acute lymphoblastic leukemia (ALL). It is investigational to use blinatumomab to treat patients with RT. The study doctor can explain how the study drug is designed to work. Up to 21 participants will be enrolled in this study. All will take part at MD Anderson.

Publications & conference data

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

  1. Clinical characteristics and outcomes of Richter transformation: experience of 204 patients from a single center.
    Wang Y, Tschautscher MA, Rabe KG, Call TG, et al · · 2020 · cited 96× · PMID 31197071 · DOI 10.3324/haematol.2019.224121
  2. Blinatumomab, a bispecific B-cell and T-cell engaging antibody, in the treatment of B-cell malignancies.
    Burt R, Warcel D, Fielding AK. · · 2019 · cited 51× · PMID 30380973 · DOI 10.1080/21645515.2018.1540828
  3. Current trends in the management of Richter's syndrome.
    Allan JN, Furman RR. · · 2018 · cited 36× · PMID 30651968 · DOI 10.2217/ijh-2018-0010
  4. Richter transformation in the era of novel agents.
    Ding W. · · 2018 · cited 34× · PMID 30504319 · DOI 10.1182/asheducation-2018.1.256
  5. Richter Transformation in Chronic Lymphocytic Leukemia: Update in the Era of Novel Agents.
    Tadmor T, Levy I. · · 2021 · cited 25× · PMID 34680290 · DOI 10.3390/cancers13205141
  6. A phase two study of high dose blinatumomab in Richter's syndrome.
    Thompson PA, Jiang X, Banerjee P, Basar R, et al · · 2022 · cited 24× · PMID 35941212 · DOI 10.1038/s41375-022-01649-3
  7. Microenvironment Remodeling and Subsequent Clinical Implications in Diffuse Large B-Cell Histologic Variant of Richter Syndrome.
    Augé H, Notarantonio AB, Morizot R, Quinquenel A, et al · · 2020 · cited 19× · PMID 33381116 · DOI 10.3389/fimmu.2020.594841
  8. T-Cell Engagers-The Structure and Functional Principle and Application in Hematological Malignancies.
    Cech P, Skórka K, Dziki L, Giannopoulos K. · · 2024 · cited 17× · PMID 38672662 · DOI 10.3390/cancers16081580

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