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

NCT ID: NCT05966233

Last Updated: 2024-05-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-31
• Study Completion Date: 2029-01-31

Brief 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. 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.

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.

Conditions

Diffuse Large B Cell Lymphoma Refractory; Diffuse Large B-cell Lymphoma Recurrent

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

R-DHAP

R-DHAP x4 + autologous transplant/salvage treatment (based on centrally review response)

Group Type: ACTIVE_COMPARATOR

R-DHAP

Intervention Type: DRUG

• 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-DHAP

Pola-R-DHAP x4 + autologous transplant/salvage treatment (based on centrally review response)

Group Type: EXPERIMENTAL

Pola-R-DHAP

Intervention Type: DRUG

• 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

Interventions

R-DHAP

• 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

Intervention Type: DRUG

Pola-R-DHAP

• 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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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
• Follicular large B-cell lymphoma (FLBL, former follicular 3b)

2. 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;

3. 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;

4. CAR-T not indicated or unavailable;

5. Age 18-70 years. sGA mandatory for patients 65-70 years old: only category FIT admitted [20] (see Appendix A);

6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 if not related to lymphoma disease (see Appendix B);

7. Measurable disease ≥ 1.5 cm in longest diameter, and measurable in 2 perpendicular dimensions;

8. 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;

9. 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;

10. Adequate renal function defined as creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula; see Appendix C)

11. Subjects HBsAg negative but positive for antibodies to hepatitis B core antigen with undetectable HBV-DNA measured by real-time polymerase chain reaction (PCR).

12. 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

13. 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;

14. Life expectancy > 6 months;

15. 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;

16. Subject must be able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria

1. Any histology other than DLBCL

2. Primary mediastinal lymphoma (PMBCL)

3. Known central nervous system lymphoma

4. Known history of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies

5. Contraindication to any drug in the chemotherapy regimen

6. Left ventricular ejection fraction (LVEF) < 50%

7. Neuropathy ≥ grade 2

8. 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

9. Any uncontrolled active systemic infection requiring intravenous (IV) antibiotics

10. History of stroke or intracranial hemorrhage within the past 6 months.

11. History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances

12. Clinically significant cardiovascular disease

13. Major surgical intervention prior 4 weeks to enrollment if not due to lymphoma and/or other disease life-threatening that can compromise chemotherapy treatment

14. 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

15. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety

16. If female, the patient is pregnant or breast-feeding

17. Patients participating in other clinical studies

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Monica Balzarotti, MD

Role: PRINCIPAL_INVESTIGATOR

Dipartimento di Oncologia Medica ed Ematologia - Istituto Clinico Humanitas - Rozzano (MI)

Locations

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

Alessandria, , Italy

AOU Ospedali Riuniti, Clinica di Ematologia

Ancona, , Italy

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

Avellino, , Italy

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

Aviano, , Italy

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

Bari, , Italy

Cliniche Humanitas Gavazzeni, Oncologia

Bergamo, , Italy

ASST Spedali Civili di Brescia, Ematologia

Brescia, , Italy

Fondazione del Piemonte per l'Oncologia - IRCCS, Ematologia

Candiolo, , Italy

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

Catania, , Italy

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

Cuneo, , Italy

Azienda Ospedaliera Universitaria Careggi, Unitа funzionale di Ematologia

Florence, , Italy

Ospedale Vito Fazzi, Ematologia

Lecce, , Italy

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

Legnano, , Italy

ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia

Milan, , Italy

Istituto Scientifico San Raffaele, Unitа Linfomi - Dipartimento Oncoematologia

Milan, , Italy

Ospedale Maggiore Policlinico - Fondazione IRCCS Ca Granda, Ematologia

Milan, , Italy

Fondazione IRCCS San Gerardo dei Tintori, Ematologia

Monza, , Italy

AOU Maggiore della Caritа di Novara, SCDU Ematologia

Novara, , Italy

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

Palermo, , Italy

Ospedale S. Maria della Misericordia, Ematologia

Perugia, , Italy

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

Pescara, , Italy

Ospedale Guglielmo da Saliceto, U.O.Ematologia

Piacenza, , Italy

AOU Pisana, U.O. Ematologia

Pisa, , Italy

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

Potenza, , Italy

Ospedale delle Croci, Ematologia

Ravenna, , Italy

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

Reggio Emilia, , Italy

AO San Giovanni Addolorata, S.C. Ematologia

Roma, , Italy

AO Sant Andrea, Ematologia

Roma, , Italy

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

Roma, , Italy

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

Roma, , Italy

Istituto Clinico Humanitas, U.O. Ematologia

Rozzano, , Italy

AOU Senese, U.O.C. Ematologia

Siena, , Italy

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

Torino, , Italy

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

Torino, , Italy

Ospedale Ca Foncello, S.C di Ematologia

Treviso, , Italy

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

Tricase, , Italy

Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), SC Ematologia

Trieste, , Italy

Countries

Italy

Other Identifiers

FIL_POLA-R-DHAP

Identifier Type: -

Identifier Source: org_study_id