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

NCT04915248 | Recruiting Phase 2

• 1 other identifier: FIL_DALYA
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 18

Brief Summary

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.

Conditions

Plasmablastic Lymphoma

Keywords

Relapsed; Refractory; Plasmablastic; lymphoma; PBL; Daratumumab; Bortezomib; Dexamethasone

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Response assessment will be done at each restaging. The best overall response will be defined as the best response between the date of beginning of therapy and the last response evaluation. Patients without response assessment (due to whatever reason) will be considered as non-responders.

  30 months

Secondary Outcomes (7)

• Progression-free survival (PFS)

  30 months

• Overall survival (OS)

  30 months

• Duration of response (DOR)

  30 months

• Number of participants with treatment-related adverse events as assessed by current version of CTCAE.

  30 months

• Rate of Complete Remission (CRR)

  30 months

Study Arms (1)

All patients registered in the DALYA trial

EXPERIMENTAL

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.

Drug: Daratumumab; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Daratumumab 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.

Also known as: Daratumumab sc

All patients registered in the DALYA trial

Bortezomib 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.

Also known as: Bortezomib sc

All patients registered in the DALYA trial

Dexamethasone 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.

Also known as: Dexamethasone os

All patients registered in the DALYA trial

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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;
• ECOG Performance Status ≤ 3;
• Age ≥ 18 years;
• Both HIV-negative and HIV-positive patients are eligible;
• HIV infection responsive to ongoing cART (combination antiretroviral therapy);
• 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.
• 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.
• 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
• Subject must be able to adhere to the study visit schedule and other protocol requirements

You may not qualify if:

• Histologic diagnosis different from confirmed plasmablastic lymphoma according to WHO 2017 and/or CD38 expression \< 5% of positive cells
• CNS involvement
• Patients with known hypersensitivity to the investigational drug or to product components or severe allergic or anaphylactic reactions to humanized products
• 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
• Concomitant Kaposi sarcoma; however, patients with only skin involvement of KS can be included.
• 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)
• 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.
• 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.
• Active ongoing infection from SARS-CoV-2.
• 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

Sponsors & Collaborators

• Janssen-Cilag S.p.A.: collaborator
• Fondazione Italiana Linfomi - ETS: lead

Study Sites (18)

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

Ancona, 60126, Italy

RECRUITING

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

Aviano, Italy

RECRUITING

A.O. Spedali Civili di Brescia - Ematologia

Brescia, Italy

RECRUITING

Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia

Florence, 50141, Italy

RECRUITING

Milano - ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia

Miano, Italy

RECRUITING

Istituto Scientifico San Raffaele, Unità Linfomi - Dipartimento Oncoematologia

Milan, Italy

RECRUITING

Monza - ASST MONZA Ospedale S. Gerardo - Ematologia

Monza, Italy

RECRUITING

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

Naples, Italy

ACTIVE NOT RECRUITING

U.O. Ematologia AO di Padova

Padua, 35128, Italy

RECRUITING

A.O. Universitaria Policlinico Giaccone Di Palermo

Palermo, 90127, Italy

NOT YET RECRUITING

Ematologia IRCCS Policlinico S. Matteo di Pavia

Pavia, Italy

RECRUITING

AO Arcispedale S.Maria Nuova Ematologia

Reggio Emilia, Italy

RECRUITING

Roma - IRCCS Spallanzani - Servizio di Ematologia in malattie infettive

Roma, Italy

NOT YET RECRUITING

Roma - Ospedale S. Camillo - Ematologia

Roma, Italy

RECRUITING

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

Terni, Italy

NOT YET RECRUITING

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

Torino, 10126, Italy

RECRUITING

Struttura Complessa di Ematologia PO TREVISO

Treviso, 31100, Italy

RECRUITING

AOU Integrata di Verona - U.O. Ematologia

Verona, 37134, Italy

RECRUITING

MeSH Terms

Conditions

Plasmablastic Lymphoma; Recurrence; Lymphoma

Interventions

daratumumab; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Andrés Ferreri, Dr.

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Agostino La Porta, Dr.

CONTACT

059 976 9915; alaporta@filinf.it

Lorenza Randi, Dr.

CONTACT

0131033153; lrandi@filinf.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2021
• First Posted: June 7, 2021
• Study Start: July 11, 2022
• Primary Completion: January 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (18)