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Diffuse Large B Cell Lymphoma RefractoryPhase 2FIL_POLARDHAPNCT05966233

R-DHAP vs POLA-R-DHAP Followed by Autologous Transplant as First Salvage Treatment in Patient With Relapsed or Refractory Diffuse Large B Cell Lymphoma

A Phase 2 study testing R-DHAP and Pola-R-DHAP in people with Diffuse Large B Cell Lymphoma Refractory and Diffuse Large B-cell Lymphoma Recurrent, run by Fondazione Italiana Linfomi - ETS at 37 sites in Italy.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Prospective, multicenter, open label, phase II randomized clinical trial in DLBCL patients relapsed or refractory to first line R-chemo, aged 18-70 years and candidate to autologous transplant. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
R-DHAP and Pola-R-DHAP
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
37 sitesItaly
Study dates
Jan 2024to Jan 2029
Phase
Phase 2
Are there results?
None posted in the registry

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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically documented diagnosis of Diffuse Large B-Cell Lymphoma Not otherwise specified (DLBCL-NOS) as defined in the 2022 edition of the World Health Organization (WHO) classification; are also admitted documented diagnosis of:
  • T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL)
  • Epstein-barr virus (EBV)-associated DLBCL
  • Double-hit and triple-hit high grade B-cell lymphomas (HGBL DH/TH)
  • High-grade B-cell lymphoma, NOS (HGBL)
  • Transformed FL not previously untreated
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  • Follicular large B-cell lymphoma (FLBL, former follicular 3b)
  • Known availability of biopsy material (at relapse/refractory or previous most recent). Re-biopsy highly encouraged even if not mandatory. Central pathology review required, but not mandatory for registration and treatment start;
  • Relapse or refractoriness after the first line R-chemo (R-CHOP o similar). Previous treatment with polatuzumab containing regimen is allowed as per clinician judgment;
  • CAR-T not indicated or unavailable;
  • Age 18-70 years. sGA mandatory for patients 65-70 years old: only category FIT admitted [20] (see Appendix A);
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 if not related to lymphoma disease (see Appendix B);
  • Measurable disease ≥ 1.5 cm in longest diameter, and measurable in 2 perpendicular dimensions;
  • Normal blood count defined as: neutrophils at least 1.500/mmc, platelets at least 75.000/mmc, haemoglobin at least 8,0 g/dL with transfusion independence, unless abnormalities due to underlying disease (bone marrow involvement), at the moment of signing informed consent;
  • Adequate liver function, assessed by baseline laboratory values; the increase to up to 2.5 ULN for transaminases and up to 1.5 ULN for bilirubin admitted for cases with documented liver involvement by lymphoma;
  • Adequate renal function defined as creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula; see Appendix C)
  • Subjects HBsAg negative but positive for antibodies to hepatitis B core antigen with undetectable HBV-DNA measured by real-time polymerase chain reaction (PCR).
  • Women of childbearing potential (WOCBP) and men must agree to use effective contraception if sexually active. Females of childbearing potential and males with female partners of reproductive potential should be advised to use effective contraception while receiving polatuzumab vedotin and for 9 months after the last dose of polatuzumab vedotin for female patients and for 6 months after the last dose of polatuzumab vedotin for male patients with female partners of reproductive potential. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal 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 post-menopausal 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. The use of condoms by male patients is required (even if surgically sterilized, i.e., status post vasectomy) unless the female partner is permanently sterile. Full sexual abstinence is admitted when this is in line with the preferred and usual lifestyle of the subject, for the same time period planned for other methods of birth control (see above). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods for the female partner) and withdrawal are not acceptable methods of contraception
  • WOCBP must have a negative serum (beta-human chorionic gonadotropin [b-hCG]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study;
  • Life expectancy > 6 months;
  • Subject understands and voluntarily signs an informed consent form approved by the National Ethics Committee 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.

Who cannot join

  • Any histology other than DLBCL
  • Primary mediastinal lymphoma (PMBCL)
  • Known central nervous system lymphoma
  • Known history of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies
  • Contraindication to any drug in the chemotherapy regimen
  • Left ventricular ejection fraction (LVEF) < 50%
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  • Neuropathy ≥ grade 2
  • Subject is:
  • Seropositive for hepatitis B, defined by a positive test for hepatitis B surface antigen [HBsAg]. 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. EXCEPTION: Patients with presence of HCV antibody, but PCR negative for HCV-RNA are eligible
  • Positive for human immunodeficiency virus (HIV) infection
  • Any uncontrolled active systemic infection requiring intravenous (IV) antibiotics
  • History of stroke or intracranial hemorrhage within the past 6 months.
  • History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances
  • Clinically significant cardiovascular disease
  • Major surgical intervention prior 4 weeks to enrollment if not due to lymphoma and/or other disease life-threatening that can compromise chemotherapy treatment
  • Prior malignancies other than lymphoma in the last 5 years with exception of currently treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix
  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety
  • If female, the patient is pregnant or breast-feeding
  • Patients participating in other clinical studies

Trial locations and contacts

37 sites in 1 country.

37 sites in 1 country

Italy37 sites

  • A.O. SS. Antonio e Biagio e Cesare Arrigo, S.C. Ematologia

    Alessandria

  • AOU Ospedali Riuniti, Clinica di Ematologia

    Ancona

  • Azienda Ospedaliera S.Giuseppe Moscati, S.C. Ematologia e Trapianto emopoietico

    Avellino

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

    Aviano

  • IRCCS Istituto Tumori Giovanni Paolo II, U.O.C Ematologia

    Bari

  • Cliniche Humanitas Gavazzeni, Oncologia

    Bergamo

  • ASST Spedali Civili di Brescia, Ematologia

    Brescia

  • Fondazione del Piemonte per l'Oncologia - IRCCS, Ematologia

    Candiolo

  • Arnas Nuovo Ospedale Garibaldi Nesima, U.O.C. Ematologia

    Catania

  • A.O. S. Croce e Carle, S.C. di Ematologia e Trapianto di Midollo Osseo

    Cuneo

  • Azienda Ospedaliera Universitaria Careggi, Unitа funzionale di Ematologia

    Florence

  • Ospedale Vito Fazzi, Ematologia

    Lecce

  • ASST Ovest Milanese - Legnano, U.O.C. Ematologia

    Legnano

  • ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia

    Milan

  • Istituto Scientifico San Raffaele, Unitа Linfomi - Dipartimento Oncoematologia

    Milan

  • Ospedale Maggiore Policlinico - Fondazione IRCCS Ca Granda, Ematologia

    Milan

  • Fondazione IRCCS San Gerardo dei Tintori, Ematologia

    Monza

  • AOU Maggiore della Caritа di Novara, SCDU Ematologia

    Novara

  • A.O. Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia

    Palermo

  • Ospedale S. Maria della Misericordia, Ematologia

    Perugia

  • P.O. Spirito Santo di Pescara, UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi

    Pescara

  • Ospedale Guglielmo da Saliceto, U.O.Ematologia

    Piacenza

  • AOU Pisana, U.O. Ematologia

    Pisa

  • A.O.R. "San Carlo", U.O. Ematologia

    Potenza

  • Ospedale delle Croci, Ematologia

    Ravenna

  • Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova, Ematologia

    Reggio Emilia

  • AO San Giovanni Addolorata, S.C. Ematologia

    Roma

  • AO Sant Andrea, Ematologia

    Roma

  • Policlinico Umberto I - Universitа "La Sapienza", Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione

    Roma

  • Policlinico Universitario Campus Bio-Medico, Ematologia - Trapianto cellule staminali - Medicina Trasfusionale e Terapia cellulare

    Roma

  • Istituto Clinico Humanitas, U.O. Ematologia

    Rozzano

  • AOU Senese, U.O.C. Ematologia

    Siena

  • A.O.U. Citta della Salute e della Scienza di Torino, Ematologia Universitaria

    Torino

  • A.O.U. Citta della Salute e della Scienza di Torino, S.C.Ematologia

    Torino

  • Ospedale Ca Foncello, S.C di Ematologia

    Treviso

  • A.O.C. Panico, U.O.C Ematologia e Trapianto

    Tricase

  • Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), SC Ematologia

    Trieste

Other trials in Italy

About this study

Official title: Phase II Randomized Clinical Trial to Evaluate the Efficacy of the Addition of Polatuzumab Vedotin to Standard Chemotherapy R-DHAP (POLA-R-DHAP) as Induction Pre-transplantation Therapy in Patients With Diffuse Large B-Cell Lymphoma Refractory/Relapsed After First Line Treatment.

Prospective, multicenter, open label, phase II randomized clinical trial in DLBCL patients relapsed or refractory to first line R-chemo, aged 18-70 years and candidate to autologous transplant. Patients will be randomized 1:1 to received 4 cycles of R-DHAP or R-DHAP plus Polatuzumab Vedotin as induction treatment plus autologous transplant.

Read the detailed description

Prospective, multicenter, open label, phase II randomized clinical trial in DLBCL patients relapsed or refractory to first line R-chemo, aged 18-70 years and candidate to autologous transplant. Patients will be randomized 1:1 to received 4 cycles of R-DHAP or R-DHAP plus Polatuzumab Vedotin as induction treatment.

PET-CT scan performed after induction be centrally review for disease response. Responding patients (CR) after induction will be addressed to receive Autologous Stem Cells Transplantation (ASCT) consolidation as per local guidelines. Patients achieving PR can proceed with ASCT or with a 3rd-line treatment, according to the physician judgment. Patients in SD/PD will be diverted to salvage strategies.

Being tested
R-DHAP, Pola-R-DHAP
Keywords
Lymphoma, Diffuse Large B cell Lymphoma, Immunochemotherapy, DLBCL, Autologous, Transplant, Relapsed, Refractory, DHAP, Rituximab, Polatuzumab Vedotin, Randomized, R-DHAP, CD79, PET, Review
Medical subject headings
Lymphoma, Lymphoma, Large B-Cell, Diffuse, Recurrence

What participants receive

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

  • R-DHAPDrug

    • Rituximab 375 mg/m2 IV on D0 or D1
    • Dexamethasone 40 mg/day IV or PO on D1-4
    • Ara-C 2 g/m2 IV on D2 (2 doses every 12h) or D2 and D3
    • Cisplatin 100 mg/ m2 IV on D1

  • Pola-R-DHAPDrug

    • Polatuzumab Vedotin 1.8 mg/kg IV on D1
    • Rituximab 375 mg/m2 IV on D0 or D1
    • Dexamethasone 40 mg/day IV or PO on D1-4
    • Ara-C 2 g/m2 IV on D2 (2 doses every 12h) or D2 and D3
    • Cisplatin 100 mg/ m2 IV on D1
Study groups in NCT05966233
Study groupRoleWhat they receive
R-DHAPActive comparatorR-DHAP x4 + autologous transplant/salvage treatment (based on centrally review response)
Receives: Drug: R-DHAP
Pola-R-DHAPExperimentalPola-R-DHAP x4 + autologous transplant/salvage treatment (based on centrally review response)
Receives: Drug: Pola-R-DHAP

What is being measured

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

  1. Progression free survival (PFS)

    Time between the randomization to first documentation of recurrence, progression or death from any cause

    Measured: From treatment start up to 30 months (6 months treatment period and 24 months of follow-up)

Secondary outcomes (7)

  1. Event-Free Survival (EFS)

    Time between the randomization to any treatment failure, including disease progression, or discontinuation of treatment for any reason (e.g., disease progression, toxicity, patient preference, initiation of a new treatment without documented progression) or death from any cause.

    Measured: From treatment start up to 30 months (6 months treatment period and 24 months of follow-up)

  2. Complete response rate (CRR)

    CRR will be defined according to Response Criteria for NHL with PET (Lugano 2014). CRR will include only patients who achieved a CR and will be evaluated on assessed patients and on all treated patients, considering patients without a response assessment (due to any reason) as non-responders.

    Measured: From treatment start up to end of treatment evaluation (about 6 months)

  3. Overall response rate (ORR)

    ORR will be defined as the proportion of patients who have a partial or complete response to therapy (CR+PR).

    Measured: From treatment start up to end of treatment evaluation (about 6 months)

  4. Overall Survival (OS)

    Time between randomization to death from any cause.

    Measured: From treatment start up to 30 months (6 months treatment period and 24 months of follow-up)

  5. Incidence and severity of AEs

    Incidence and severity of AEs in R-DHAP vs POLA-R-DHAP according to latest CTCAE criteria during induction immunochemotherapy

    Measured: From start to end of induction treatment evaluation (about 3 months)

  6. Adequate stem cells mobilization

    Adequate stem cells mobilization will be defined by the target cell harvesting of 3 x 10^6 CD34+ cells/kg

    Measured: From beginning of 2nd cycle to end of induction treatment evaluation (about 2 months)

  7. Autologous consolidation feasibility

    Proportion of patients receiving autologous consolidation after POLA-R-DHAP vs R-DHAP

    Measured: At time of end of treatment assessment (up to 6 months from treatment begin)

Timeline

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

  1. First posted28 Jul 2023
  2. Study startJan 2024 (estimated)
  3. Primary completionJan 2029 (estimated)
  4. Study completionJan 2029 (estimated)

Why it stopped: Sponsor decision

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05966233
Sponsor's protocol ID
FIL_POLA-R-DHAP
Acronym
FIL_POLARDHAP
Status last verified
May 2024
First submitted
21 Jul 2023
Last updated
21 May 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing R-DHAP and Pola-R-DHAP in people with Diffuse Large B Cell Lymphoma Refractory and Diffuse Large B-cell Lymphoma Recurrent, run by Fondazione Italiana Linfomi - ETS at 37 sites in Italy.

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 22 inclusion and 20 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: withdrawn, as of the sponsor's last update on 21 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in Italy. 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Progression free survival (PFS) (time frame: From treatment start up to 30 months (6 months treatment period and 24 months of follow-up)). 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 NCT05966233.

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 21 May 2024.

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