Ireland
--:--IST
Recruiting Phase 2

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

NCT04915248 · tracked via the Priya Life Science Italy tracker
Phase
Phase 2
Started
2022-07-11
Last updated
2026-09-09

Condition(s) studied

Plasmablastic Lymphoma

Investigational drug(s) / intervention(s)

Daratumumab →Bortezomib →Dexamethasone →

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.

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.

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.

Study 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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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

Primary outcome measure(s)

  • Overall response rate (ORR) — 30 months
    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.

Trial sites (18)

FacilityCityRegionStatus
A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona Ancona Ancona Recruiting
Aviano - IRCCS Centro di Riferimento Oncologico di Aviano - Divisione di Oncologia e dei Tumori immuto-correlati Aviano Aviano Recruiting
Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia Florence Firenze Recruiting
Milano - ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia Miano 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
Roma - IRCCS Spallanzani - Servizio di Ematologia in malattie infettive Roma Italy Not Yet Recruiting
Roma - Ospedale S. Camillo - Ematologia Roma Italy Recruiting
A.O. Universitaria Policlinico Giaccone Di Palermo Palermo Palermo Not Yet Recruiting
A.O. Universitaria Citta' Della Salute E Della Scienza Di Torino Torino Torino Recruiting
Struttura Complessa di Ematologia PO TREVISO Treviso Treviso Recruiting
AOU Integrata di Verona - U.O. Ematologia Verona Verona Recruiting
A.O. Spedali Civili di Brescia - Ematologia Brescia Italy Recruiting
Istituto Scientifico San Raffaele, Unità Linfomi - Dipartimento Oncoematologia Milan Italy Recruiting
U.O. Ematologia AO di Padova Padova Italy Recruiting
Ematologia IRCCS Policlinico S. Matteo di Pavia Pavia Italy Recruiting
AO Arcispedale S.Maria Nuova Ematologia Reggio Emilia Italy Recruiting
A.O. S. Maria di Terni - S.C. Oncoematologia Terni Italy Not Yet Recruiting

Other trials for the same condition

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04915248 on ClinicalTrials.gov ↗ ← All trials in Italy