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An Investigator-Initiated, Phase II, Multicenter, Open-Label, Single-Arm, Prospective Clinical Trial to Evaluate the Efficacy and Safety of Alternating Bortezomib-Based Regimens in Combination With DaratUMumab Followed by Maintenance With Daratumumab in the Frontline Setting of Primary Plasma CEll L

Phase 2
Recruiting
Conditions
Primary Plasma Cell Leukemia
Interventions
Registration Number
NCT06636552
Lead Sponsor
Hellenic Society of Hematology
Brief Summary

The primary objective of this study is to evaluate the efficacy of the alternating D-PAD/D-CVD induction regimen followed by D-CVD consolidation regimen and maintenance with daratumumab monotherapy, in terms of PFS, in the first-line setting of pPCL.

Detailed Description

This is an investigator-initiated, prospective, multicenter, phase II, open-label, single-arm, non-randomized, single-stage clinical trial.

The study comprises the following phases:

A 28-day screening phase An induction phase which includes six 21-day induction treatment cycles of alternating D-PAD and D-CVD (starting with D-PAD) Note: Based on the post-induction treatment disease evaluation, transplant-eligible subjects who have achieved ≥SD and PBPC ≤2% will undergo ASCT whereas those with SD or PBPC 2% will discontinue study treatment. Accordingly, transplant-eligible subjects who have achieved ≥PR will receive 2 additional D-CVD cycles whereas those with \<PR will discontinue study treatment.

ASCT (single or tandem) (applicable for transplant-eligible patients) A consolidation phase which includes two 21-day consolidation cycles of D-CVD A maintenance phase which includes twenty-four 28-day cycles of daratumumab monotherapy (applicable for subjects who have achieved ≥PR at the end of consolidation phase \[Cycle 8\]) An End of Treatment (EOT) visit: 30 days (±7 days) after the last dose of all components of the study treatment have been discontinued

A Post-Treatment Follow-Up (PTFU) phase which will begin once a subject permanently discontinues study treatment. In particular:

All subjects who complete or discontinue study treatment without disease progression (PD), will return to the site every 12 weeks (±2 weeks) for disease evaluation (or sooner at Investigator's discretion if there are concerns for progression/relapse) and other follow-up assessments until the earliest of confirmed PD, start of subsequent therapy for PCL, death, or the end of study (EOS) definition is met.

After confirmed PD or the start of a new anticancer treatment for PCL, subjects will return to the site or be contacted by telephone every 16 weeks (±2 weeks) for collection of follow-up information (i.e., other malignancies, next-line therapy, and survival, as applicable) until death, withdrawal of consent for study participation, or the EOS definition is met, whichever occurs first.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
43
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Single-armDaratumumab (Subcutaneously)* A consolidation phase which includes two 21-day consolidation cycles of D-CVD * A maintenance phase which includes twenty-four 28-day cycles of daratumumab monotherapy (applicable for subjects who have achieved ≥PR at the end of consolidation phase \[Cycle 8\])
Primary Outcome Measures
NameTimeMethod
Εfficacy of the alternating D-PAD/D-CVD induction regimen followed by D-CVD consolidation regimen and maintenance with daratumumab monotherapy, in terms of PFS, in the first-line setting of pPCL.Approximately 28 months (including induction/consolidation/maintenance phase and excluding transplantation) [168 days induction/consolidation plus 672 days maintenance].

Duration from the date of induction treatment initiation to the date of first documented evidence of progressive disease (PD) (assessed by the IMWG criteria) or death, whichever occurs earlier.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (7)

1st Propaedeutic Department, "Laiko" General Hospital of Athens

🇬🇷

Athens, Attica, Greece

Hematology Clinic, General Hospital of Athens "Evanggelismos"

🇬🇷

Athens, Attica, Greece

Hematology Department "Alexandra" General Hospital of Athens

🇬🇷

Athens, Attica, Greece

Hematology Department, University General Hospital of Alexandroupolis

🇬🇷

Alexandroupolis, Evros, Greece

Hematology Department, Regional General Hospital for Cancer Treatment "Metaxa" of Piraeus

🇬🇷

Piraeus, Greece

Hematology Department, General Hospital of Thessaloniki "Papanikolaou"

🇬🇷

Thessaloniki, Greece

Hematology Department, Theageneion Cancer Hospital

🇬🇷

Thessaloniki, Greece

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