Study to Evaluate Combined Treatment of Daratumumab, Bortezomib and Dexamethasone in PBL Patients.

NCT ID: NCT04915248

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-11

Study Completion Date

2027-06-01

Brief Summary

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It is an open-label, multicenter, phase II, single arm trial to Evaluate Activity and Safety of Daratumumab in combination with Bortezomib and Dexamethasone in patients about 28 patients with Relapsed or Refractory Plasmablastic lymphoma.

Detailed Description

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This is an open-label, multicenter, phase II, single arm trial. Patients will be recruited over 18 months in 19 FIL centers and it is expected that a total of 28 patients will start treatment. Analysis of the primary endpoint of the study is planned approximately after 12 months from the enrollment of the last patient, regardless of the response to protocol treatment of this patient. The total duration of the study is 30 months (\~2.5 years).

Patients will be enrolled based on the local diagnosis and the local assessment of CD38 expression ≥ 5%. The screening phase of the study includes baseline assessments according to local practice and those required by the study.

Samples coming from the most recent biopsy, and if available also those used for the first diagnosis, are to be collected and sent afterwards, upon request of the FIL Offices, to one of the three FIL designed central laboratories. Central diagnosis review and CD38 assessment will be performed during or at the end of the study conductance; there's no need to wait for central results to start protocol treatment.

Protocol treatment consists of an induction phase planning one course (cycle 1) of daratumumab sc as single agent followed by 8 courses (cycles 2-9) of daratumumab sc in combination with bortezomib sc and dexamethasone (DVd regimen).

Patients achieving at least a SD after induction will be addressed to the maintenance phase, planning a maximum of 6 cycles (cycles 10-15) of daratumumab sc as single agent.

Induction cycles will be administered every 21 days, while maintenance cycles will be administered every 28 days.

Treatment with DVd or daratumumab single agent will be discontinued before completion of planned cycles in case of disease progression, unacceptable toxicity, withdrawal of consent and/or the investigator determines that further therapy is not in the patient best interest (e.g., due to non-compliance, toxicity, etc.). Adverse events according to CTCAE will be monitored from the first dose of induction treatment, throughout maintenance phase and for 30 days after the last dose of protocol treatment with the study drug or 30 days after the last dose of drug in case of early discontinuation from any cause.

Conditions

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Plasmablastic Lymphoma

Keywords

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Dexamethasone Relapsed Refractory Plasmablastic lymphoma PBL Daratumumab Bortezomib

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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All patients registered in the DALYA trial

Treatment consists of an induction phase (every 21 days) planning one course (cycle 1) of daratumumab as single agent followed by 8 courses (cycles 2-9) of daratumumab in combination with bortezomib and dexamethasone (DVd regimen).

Patients achieving at least a SD after induction will be addressed to the maintenance phase (every 28 days), planning a maximum of 6 cycles (cycles 10-15) of daratumumab as single agent until disease progression, unacceptable toxicity, withdrawal of consent and/or the investigator decision.

Group Type EXPERIMENTAL

Daratumumab

Intervention Type DRUG

Induction phase planning one course (cycle 1) of daratumumab as single agent followed by 8 courses (cycles 2-9) of daratumumab in combination with bortezomib and dexamethasone (DVd regimen).

Patients achieving at least a SD after induction will be addressed to the maintenance phase, planning a maximum of 6 cycles (cycles 10-15) of daratumumab as single agent.

Bortezomib

Intervention Type DRUG

Induction phase planning one course (cycle 1) of daratumumab as single agent followed by 8 courses (cycles 2-9) of daratumumab in combination with bortezomib and dexamethasone (DVd regimen).

Patients achieving at least a SD after induction will be addressed to the maintenance phase, planning a maximum of 6 cycles (cycles 10-15) of daratumumab as single agent.

Dexamethasone

Intervention Type DRUG

Induction phase planning one course (cycle 1) of daratumumab as single agent followed by 8 courses (cycles 2-9) of daratumumab in combination with bortezomib and dexamethasone (DVd regimen).

Patients achieving at least a SD after induction will be addressed to the maintenance phase, planning a maximum of 6 cycles (cycles 10-15) of daratumumab as single agent.

Interventions

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Daratumumab

Induction phase planning one course (cycle 1) of daratumumab as single agent followed by 8 courses (cycles 2-9) of daratumumab in combination with bortezomib and dexamethasone (DVd regimen).

Patients achieving at least a SD after induction will be addressed to the maintenance phase, planning a maximum of 6 cycles (cycles 10-15) of daratumumab as single agent.

Intervention Type DRUG

Bortezomib

Induction phase planning one course (cycle 1) of daratumumab as single agent followed by 8 courses (cycles 2-9) of daratumumab in combination with bortezomib and dexamethasone (DVd regimen).

Patients achieving at least a SD after induction will be addressed to the maintenance phase, planning a maximum of 6 cycles (cycles 10-15) of daratumumab as single agent.

Intervention Type DRUG

Dexamethasone

Induction phase planning one course (cycle 1) of daratumumab as single agent followed by 8 courses (cycles 2-9) of daratumumab in combination with bortezomib and dexamethasone (DVd regimen).

Patients achieving at least a SD after induction will be addressed to the maintenance phase, planning a maximum of 6 cycles (cycles 10-15) of daratumumab as single agent.

Intervention Type DRUG

Other Intervention Names

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Daratumumab sc Bortezomib sc Dexamethasone os

Eligibility Criteria

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Inclusion Criteria

1. Histologically confirmed plasmablastic lymphoma according to WHO 2017, CD38-positive by immunohistochemistry (≥5% of positive cells) Local diagnosis of PBL and local CD38 assessment ≥5% will suffice for enrollment and start of treatment.
2. Patients with plasmablastic lymphoma relapsed or refractory:

* after at least one line of conventional-dose chemotherapy followed or not by autologous stem cell transplantation;
* after at least one line of conventional-dose chemotherapy and not eligible for salvage autologous or allogeneic transplantation;
3. ECOG Performance Status ≤ 3;
4. Age ≥ 18 years;
5. Both HIV-negative and HIV-positive patients are eligible;
6. HIV infection responsive to ongoing cART (combination antiretroviral therapy);
7. At least one measurable disease lesion identifiable by imaging:

* A nodal lesion must be at least 11 mm x 11 mm OR ≥ 16 mm in the greatest transverse diameter (regardless of short axis measurement).
* An extranodal lesion must be at least 10 mm x 10 mm.
8. Women of childbearing potential (WOCBP) and men must agree to use effective contraception if sexually active. This applies for the time period between signing of the informed consent form and 7 months (for women) o 4 months (for men) after last administration of bortezomib or 6 months after last daratumumab dose, regardless of sex. A woman is considered of childbearing potential, i.e., fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for continuous 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control method (failure rate of less than 1%) e.g., intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, and sexual abstinence. The use of condoms by male patients is required unless the female partner is permanently sterile.

WOCBP must have two negative pregnancy tests as verified by the study doctor prior to starting study therapy and must agree to undergo monthly pregnancy testing during the course of the study and after end of study therapy if clinically indicated. This applies even if the subject practices complete abstinence from heterosexual contact.
9. Subject understands and voluntarily signs and dates an informed consent form approved by an Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures
10. Subject must be able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria

1. Histologic diagnosis different from confirmed plasmablastic lymphoma according to WHO 2017 and/or CD38 expression \< 5% of positive cells
2. CNS involvement
3. Patients with known hypersensitivity to the investigational drug or to product components or severe allergic or anaphylactic reactions to humanized products
4. Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy including targeted small molecule agents within 14 days prior to the first dose of study drug
5. Concomitant Kaposi sarcoma; however, patients with only skin involvement of KS can be included.
6. Subject is:

* Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]. Subjects with resolved infection (i.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[HBcAb\] ± antibodies to hepatitis B surface antigen \[HBsAb\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (HBsAb positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
* Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy)
7. Any history of another cancer during the last 5 years with the exception of non-melanoma skin tumors, in situ cervical carcinoma, or in situ breast cancer treated with curative intent with no history of metastatic disease.
8. Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis or tuberculosis. Drugs for HIV treatment are allowed, as per local investigator prescription.
9. Active ongoing infection from SARS-CoV-2.
10. Screening laboratory values (due to causes different than lymphoma):

* Absolute neutrophil count (ANC) \<1.0 x 109/L (unless secondary to documented marrow involvement by lymphoma)
* Platelet count \<75 x 109/L
* Hemoglobin \< 7.5 g/dL
* Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) \> 3.5 times the upper limit of normal (ULN)
* Alkaline phosphatase \> 3.5 times ULN
* Bilirubin \> 2 times x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
* Serum Creatinine Clearance \< 20 ml/h
11. Subject has clinically significant cardiac disease, including:

* Myocardial infarction within 6 months before date of registration, or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV)
* Cardiac arrhythmia (Common Terminology Criteria for Adverse Events \[CTCAE\] current version Grade 2 or higher) or clinically significant ECG abnormalities. Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) \> 470 msec
12. Evidence of any other clinically significant uncontrolled condition(s)
13. Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent
14. Breastfeeding women or women with a positive pregnancy test at screening
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen-Cilag S.p.A.

INDUSTRY

Sponsor Role collaborator

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andrés Ferreri, Dr.

Role: PRINCIPAL_INVESTIGATOR

Unità Linfomi - Dipartimento Oncoematologia -Istituto Scientifico San Raffaele - Milano

Locations

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A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona

Ancona, , Italy

Site Status RECRUITING

Aviano - IRCCS Centro di Riferimento Oncologico di Aviano - Divisione di Oncologia e dei Tumori immuto-correlati

Aviano, , Italy

Site Status RECRUITING

A.O. Spedali Civili di Brescia - Ematologia

Brescia, , Italy

Site Status RECRUITING

Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia

Florence, , Italy

Site Status RECRUITING

Milano - ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia

Miano, , Italy

Site Status RECRUITING

Istituto Scientifico San Raffaele, Unità Linfomi - Dipartimento Oncoematologia

Milan, , Italy

Site Status RECRUITING

Monza - ASST MONZA Ospedale S. Gerardo - Ematologia

Monza, , Italy

Site Status RECRUITING

Napoli - AORN - Azienda Ospedaliera dei Colli Monald - U.O.C. Oncologia

Napoli, , Italy

Site Status ACTIVE_NOT_RECRUITING

U.O. Ematologia AO di Padova

Padua, , Italy

Site Status RECRUITING

A.O. Universitaria Policlinico Giaccone Di Palermo

Palermo, , Italy

Site Status NOT_YET_RECRUITING

Ematologia IRCCS Policlinico S. Matteo di Pavia

Pavia, , Italy

Site Status RECRUITING

AO Arcispedale S.Maria Nuova Ematologia

Reggio Emilia, , Italy

Site Status RECRUITING

Roma - IRCCS Spallanzani - Servizio di Ematologia in malattie infettive

Roma, , Italy

Site Status NOT_YET_RECRUITING

Roma - Ospedale S. Camillo - Ematologia

Roma, , Italy

Site Status RECRUITING

A.O. S. Maria di Terni - S.C. Oncoematologia

Terni, , Italy

Site Status NOT_YET_RECRUITING

A.O. Universitaria Citta' Della Salute E Della Scienza Di Torino

Torino, , Italy

Site Status RECRUITING

Struttura Complessa di Ematologia PO TREVISO

Treviso, , Italy

Site Status RECRUITING

AOU Integrata di Verona - U.O. Ematologia

Verona, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Agostino La Porta, Dr.

Role: CONTACT

Phone: 059 976 9915

Email: [email protected]

Lorenza Randi, Dr.

Role: CONTACT

Phone: 0131033153

Email: [email protected]

Facility Contacts

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Role: primary

Role: primary

Alessandro Re, MD

Role: primary

Luca Nassi, Dott.

Role: primary

Role: primary

Andrés Ferreri

Role: primary

Role: primary

Francesco Piazza

Role: primary

Role: primary

Role: primary

Role: primary

[email protected]

Role: primary

Role: primary

Anna Marina Liberati, Prof

Role: primary

Role: backup

Role: primary

Piero Maria Stefani, MD

Role: primary

Francesca Maria Quaglia, Dott.ssa

Role: primary

Other Identifiers

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FIL_DALYA

Identifier Type: -

Identifier Source: org_study_id