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High-risk Diffuse Large B-Cell LymphomaPhase 2NCT03023878

Safety and Efficacy of Blinatumomab in Adults With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma

A Phase 2 study testing Blinatumomab, Investigator's Choice Chemotherapy and Dexamethasone in people with High-risk Diffuse Large B-Cell Lymphoma, run by Amgen at 24 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

A phase 2, multicenter, open-label, single arm clinical trial in adults with newly diagnosed aggressive high-risk DLBCL. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
High-risk Diffuse Large B-Cell Lymphoma
What is being tested?
Blinatumomab, Investigator's Choice Chemotherapy and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
24 sitesin 6 countries
Study dates
13 Mar 2017to 28 Oct 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject has provided informed consent prior to initiation of any study-specific activities/procedures
  • Age ≥ 18 at time of informed consent
  • Subject must have untreated histologically proven high-risk DLBCL defined by atleast one of the following:
  • International Prognostic Index (IPI) for Diffuse Large B-cell Lymphoma 3 to 5 (representing high intermedidate - high ratings),
  • Double-hit or higher or double protein expression
  • Eastern Cooperative Oncology Group performance status ≤ 2.
Show all 12Show fewer
  • Subject meets the criteria per investigator's institution to receive standard of care (SOC) rituximab-chemotherapy (ie, R-CHOP [14 or 21] or R-DA-EPOCH or R-CHOEP) of 6 cycles. Subjects may be enrolled on study prior to cycle 1 or cycle 2 of SOC R-chemotherapy
  • Adequate organ and bone marrow function determined within 14 days prior to enrollment defined as:
  • Hematological: Absolute neutrophil count ≥1*10^9/L; Platelet count ≥75*10^9/L;Hemoglobin ≥8g/dL
  • Renal: Creatinine clearance ≥50mL/min;
  • Hepatic: Aspartate aminotransferase/Alanine aminotransferase <3*upper limit of normal (ULN); Total bilirubin <2*ULN (unless Gilbert's Disease or if liver involvement with lymphoma)
  • Subject must have completed 6 cycles of SOC R-chemotherapy and achieved CR, PR or stable disease by PET/CT performed 3 weeks (± 3 days) after cycle 6 of SOC R-chemotherapy. Subjects with progressive disease (PD) are not eligible for treatment with blinatumomab and will end the study.

Who cannot join

  • Clinically relevant central nervous system (CNS) pathology requiring treatment such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis
  • Evidence of CNS involvement with DLBCL at disease evaluation obtained prior to starting blinatumomab
  • Current autoimmune disease or history of autoimmune disease with potential of CNS involvement
  • Subject has active infection requiring systemic therapy
  • Prior anti-CD19 therapies
  • Known infection with HIV or chronic infection with hepatitis B virus or hepatitis C virus
Show all 18Show fewer
  • History of other malignancy within the past 3 years with the following exceptions:
  • Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician
  • Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease
  • Adequately treated cervical carcinoma in situ without evidence of disease
  • Adequately treated breast ductal carcinoma in situ without evidence of disease
  • Prostatic intraepithelial neoplasia without evidence of prostate cancer
  • Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ
  • Subject has known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing.
  • Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge.
  • History/evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
  • Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed while receiving blinatumomab and for an additional 48 hours after the last treatment dose of blinatumomab.
  • Currently receiving treatment in another investigational device or drug study or less than 30 days since ending treatment on another investigational device or drug study. Other investigational procedures while participating in this study are excluded.

Trial locations and contacts

24 sites in 6 countries.

24 sites in 6 countries

United States8 sites
  • Research Site

    Baltimore, Maryland, 21201

  • Research Site

    Chicago, Illinois, 60612

  • Research Site

    Greenville, South Carolina, 29607

  • Research Site

    Maywood, Illinois, 60153

  • Research Site

    New Brunswick, New Jersey, 08903

  • Research Site

    New Orleans, Louisiana, 70112

  • Research Site

    Oklahoma City, Oklahoma, 73104

  • Research Site

    Portland, Oregon, 97213

Other trials in United States

Spain7 sites
  • Research Site

    A Coruña, Galicia, 15006

  • Research Site

    Barcelona, Catalonia, 08003

  • Research Site

    L'Hospitalet de Llobregat, Catalonia, 08907

  • Research Site

    Madrid, 28007

  • Research Site

    Salamanca, Castille and León, 37007

  • Research Site

    Seville, Andalusia, 41013

  • Research Site

    Valencia, Valencia, 46026

Other trials in Spain

Canada3 sites
  • Research Site

    Edmonton, Alberta, T6G 1Z2

  • Research Site

    Sault Ste. Marie, Ontario, P6B 0A8

  • Research Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

France2 sites
  • Research Site

    Créteil, 94010

  • Research Site

    Paris, 75475

Other trials in France

Germany2 sites
  • Research Site

    Dresden, 01307

  • Research Site

    Ulm, 89081

Other trials in Germany

United Kingdom2 sites
  • Research Site

    Bristol, BS2 8ED

  • Research Site

    Sheffield, S10 2JF

Other trials in United Kingdom

About this study

Official title: 20150288 A Phase 2 Open-label Study Investigating the Safety and Efficacy of Blinatumomab After Frontline R-Chemotherapy in Adult Subjects With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma (DLBCL)

A phase 2, multicenter, open-label, single arm clinical trial in adults with newly diagnosed aggressive high-risk DLBCL.

Read the detailed description

The safety profile of blinatumomab after frontline rituximab (R)-chemotherapy, consisting of either R-CHOP (14 or 21) (rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone) or R-DA-EPOCH (rituximab and dose adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), or R-CHOEP (rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide), will be determined. The study will consist of a screening period of up to 14 days, a standard of care (SOC) R-chemotherapy run-in period of approximately 21 weeks, a 12 to 16 week blinatumomab treatment period, a 30-day safety follow-up visit, and a long-term follow-up period that begins after the safety follow-up visit is completed until 1 year from the first dose blinatumomab.

Being tested
Blinatumomab, Investigator's Choice Chemotherapy, Dexamethasone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BlinatumomabDrug

    Also called AMG103, BlinCyto

    Blinatumomab monotherapy was supplied in single-use sterile glass injection vials and administered as an IV infusion.

  • Investigator's Choice ChemotherapyDrug

    During the run-in period participants received 6 cycles of standard of care rituximab-chemotherapy dosed per investigator's institution standard as follows:

    • R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine,prednisone)
    • R-DA-EPOCH (rituximab and dose adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) or
    • R-CHOEP (rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide).
  • DexamethasoneDrug

    Also called corticosteroid

    Dexamethasone 20 mg IV: within 1 hour prior to start of treatment in each treatment cycle, and within 1 hour prior to dose-step (increase).

Study groups in NCT03023878
Study groupRoleWhat they receive
BlinatumomabExperimentalBlinatumomab was administered as a continuous intravenous (IV) infusion. Cycle 1 was 12 weeks (84 days) in duration with step dosing of 9 µg/day for 7 days, 28 µg/day for 7 days, 112 µg/day for 6 weeks, followed by a 4-week treatment free time. An optional 4-week Cycle 2 of blinatumomab was available for participants whose disease did not progress, with step dosing of 9 µg/day for 7 days, 28 µg/day for 7 days, and 112 µg/day for 14 days. There was a safety follow-up for 30 days. And a long-term follow-up of up to 8 months for a maximum of 1 year from first dose of blinatumomab or until participant death.
Receives: Drug: Blinatumomab; Drug: Investigator's Choice Chemotherapy; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Participants With Treatment-Emergent (Blinatumomab) Adverse Events

    Overall incidence and severity of treatment-emergent adverse events occurring during the blinatumomab investigative product (IP) treatment period graded by investigators according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and based on the scale:

    Grade 1 = Mild - transient or mild discomfort; Grade 2 = Moderate - mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required; Grade 3 = Severe - marked limitation in activity, assistance usually required; medical intervention required, hospitalization is possible; Grade 4 = Life threatening - extreme limitation in activity, assistance required; medical intervention, hospitalization or hospice care probable; Grade 5 = death.

    Measured: From the start of first infusion of IP to 30 days after the end of last infusion of IP; median (min, max) treatment duration was 56 (16, 84) days

  2. Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment

    Overall incidence and severity of treatment-emergent adverse events deemed by investigators to be related to blinatumomab treatment. Severity was graded by investigators according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and based on the scale:

    Grade 1 = Mild - transient or mild discomfort; Grade 2 = Moderate - mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required; Grade 3 = Severe - marked limitation in activity, assistance usually required; medical intervention required, hospitalization is possible; Grade 4 = Life threatening - extreme limitation in activity, assistance required; medical intervention, hospitalization or hospice care probable; Grade 5 = death.

    Measured: From the start of first infusion of IP to 30 days after the end of last infusion of IP; median (min, max) treatment duration was 56 (16, 84) days

Secondary outcomes (8)
  1. Overall Objective Response Rate (ORR) Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) and Partial Metabolic Response (PMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period

    Tumor response assessment was performed by a central reader according to modified Lugano classification using PET/CT scan. Overall objective response rate (ORR) is the percentage of participants with a best overall response of complete metabolic response (CMR) or partial metabolic response (PMR). CMR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with/without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PMR: a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline.

    Measured: Cycle 1: Day 78 (3 weeks following end of Cycle 1 IP treatment) Treatment Period: Either the Cycle 1 timeframe or approximately Day 128 (3 weeks after Cycle 2 ended) for participants who completed Cycle 2

  2. Kaplan-Meier Estimates for Duration of Response

    Duration of response was calculated only for responders during cycle 1. For participants who had CR or PR on the PET/CT scan at the end of the run-in period, response was measured from the start of blinatumomab treatment. For participants who had stable disease at the end of the run-in period, duration was calculated from documentation of the first assessment of either PR or CR on blinatumomab.

    Progression was defined as the first diagnosis of progressive metabolic response/progressive disease based on PET/CT scan per central or investigator review during the treatment period or relapse based on clinical tumor assessment during the long-term follow up period.

    Response duration was calculated until the start of new anti-tumor treatment (excluding any stem cell transplantation), PD, or death, whichever was the earliest event. Participants who did not have new anti-tumor treatment (excluding stem cell transplantation), PD, or death were censored at the last tumor assessment date.

    Measured: The median (range) follow-up time was 11.5 (8.2, 14.5) months

  3. Complete Response Rate Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period

    Tumor response assessment was performed by a central reader according to modified Lugano classification using PET/CT scan.

    CMR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with/without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology.

    Measured: Cycle 1: Day 78 (3 weeks following end of Cycle 1 IP treatment) Treatment Period: Either the Cycle 1 timeframe or approximately Day 128 (3 weeks after Cycle 2 ended) for participants who completed Cycle 2

  4. Kaplan-Meier Estimates for Overall Survival (OS) From First Dose of Blinatumomab

    OS was calculated as the time from the date of first IP infusion until death due to any cause. Participants who are alive at the date that triggers the analysis were censored at the date last known to be alive.

    Months were calculated as days from the first dose date of blinatumomab to death/censor date, divided by 30.5.

    Measured: The median (range) follow-up time was 12.0 (10.7, 14.5) months.

  5. Kaplan-Meier Estimates for Progression Free Survival (PFS) From First Dose of Blinatumomab

    PFS was calculated as the time from the date of first IP infusion until the date of diagnosis of progression of DLBCL or the date of death, whichever was the earliest. The diagnosis of progression of DLBCL was defined as the first diagnosis of progressive metabolic response/progressive disease based on PET/CT scan per central or investigator review during the treatment period or relapse based on clinical tumor assessment during the long-term follow up period. Participants who were alive and did not have progression were censored at the last evaluable non-missing tumor assessment date prior to the analysis trigger date.

    Measured: The median (range) follow-up time was 12.0 (8.2, 14.5)

  6. Percentage of Participants Who Had Hematopoietic Stem Cell Transplantation (HSCT)

    Percentage of participants who had HSCT during the Long Term Follow-Up Period.

    Measured: Day 1 up to 14.5 months

  7. Pharmacokinetics (PK) Results for Blinatumomab: Steady-State Concentrations at Week 1, Week 2 and Week 3 for Cycle 1

    The steady-state serum concentration (Css), summarized as the observed concentrations collected after at least 10 hours after the start of continuous IV infusion.

    PK blood samples were analyzed in a central lab.

    Measured: Day 2 at least 24 hours after blinatumomab was started and on Day 9 and Day 16 at least 24 hours after blinatumomab dose was increased in the cycle

  8. Pharmacokinetics (PK) Results for Blinatumomab: Clearance for Cycle 1

    PK blood samples were analyzed in a central lab.

    Measured: Day 2 at least 24 hours after blinatumomab was started and on Day 9 and Day 16 at least 24 hours after blinatumomab dose was increased in the cycle

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2017 (estimated)
  2. Study start13 Mar 2017
  3. Primary completion4 Apr 2019
  4. Study completion28 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03023878
Sponsor's protocol ID
20150288
Other IDs
2016-002190-35, 2016
Status last verified
Aug 2020
First submitted
12 Dec 2016
Last updated
14 Sep 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Publications

  • Katz DA, Morris JD, Chu MP, David KA, Thieblemont C, Morley NJ, Khan SS, Viardot A, Martin Garcia-Sancho A, Rodriguez-Garcia G, Bastos-Oreiro M, Lee ST, Kormany W, Chen Y, Wong HL, Anderson AA, Katlinskaya Y, Avilion AA, Dai T, Gonzalez-Barca E. Open-label, phase 2 study of blinatumomab after frontline R-chemotherapy in adults with newly diagnosed, high-risk DLBCL. Leuk Lymphoma. 2022 Sep;63(9):2063-2073. doi: 10.1080/10428194.2022.2064981. Epub 2022 May 3.

    PubMed 35503708

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Blinatumomab, Investigator's Choice Chemotherapy and Dexamethasone in people with High-risk Diffuse Large B-Cell Lymphoma, run by Amgen at 24 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Spain, Canada, France, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Participants With Treatment-Emergent (Blinatumomab) Adverse Events (time frame: From the start of first infusion of IP to 30 days after the end of last infusion of IP; median (min, max) treatment duration was 56 (16, 84) days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03023878, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2020.

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