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

NCT06636552 | Recruiting Phase 2

• 1 other identifier: 54767414LEU2002
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 7

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.

Conditions

Primary Plasma Cell Leukemia

Keywords

primary plasma cell leukemia

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  Approximately 28 months (including induction/consolidation/maintenance phase and excluding transplantation) [168 days induction/consolidation plus 672 days maintenance].

Study Arms (1)

Single-arm

OTHER

* 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 \[Cycle 8\])

Drug: Daratumumab (Subcutaneously)

Interventions

Daratumumab (Subcutaneously) DRUG

D-PAD (21-Day Cycles 1, 3 and 5): 1,800 mg (QW) SC on days 1, 8, and 15 (for Cycles 1 and 3) 1,800 mg (Q3W) SC on day 1 (for Cycle 5) D-CVD (21-Day Cycles 2, 4, 6, 7 and 8): 1,800 mg (QW) SC on days 1, 8, and 15 (for Cycle 2) 1,800 mg (Q3W) SC on day 1 (for Cycles 4, 6, 7 and 8) Daratumumab monotherapy (28-Day Cycles 9 to 32): 1,800 mg (Q4W) SC on day 1

Single-arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 80 years (inclusive) at the time of signing the informed consent.
• Patients newly diagnosed with documented pPCL as defined by the current IMWG criteria for PCL and MM:
• Documented presence of ≥5% PBPCs and/or absolute number ≥0.5 × 103/μL, assessed either morphologically in the peripheral blood (PB) smear or by flow cytometry, and confirmation of plasma cell clonality by flow cytometry
• Clonal BMPCs ≥10% or biopsy-proven bony or extramedullary plasmacytoma
• At least one of the following myeloma defining events:
• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically (one or more of the following):
• Hypercalcemia: serum calcium \>0.25 mmol/L (\>1 mg/dL) higher than the upper limit of normal (ULN) or \>2.75 mmol/L (\>11 mg/dL)
• Renal insufficiency: Creatinine clearance (CrCl) \<40 mL/min (measured or estimated by validated equations) or serum creatinine \>177 μmol/L (\>2 mg/dL)
• Anemia: hemoglobin value of \>20 g/L below the lower limit of normal (LLN), or a hemoglobin value \<100 g/L
• Bone lesions: One or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)-CT.
• Any one or more of the following biomarkers of malignancy:
• Clonal bone marrow plasma cell percentage ≥60%
• Involved:Uninvolved serum free light chain (sFLC) ratio ≥100 \>1 focal lesions on MRI studies (each focal lesion must be 5 mm or more in size).
• Measurable disease by protein electrophoresis as defined by any of the following:
• Serum M-protein level:

You may not qualify if:

• Patients with secondary PCL.
• Prior or concurrent invasive malignancy (other than PCL) within 5 years of date of study treatment initiation except for the following:
• Malignancy treated with curative intent and with no known active disease present for ≥3 years before study treatment initiation.
• Adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix or breast, incidental histologic finding of prostate cancer (T1a or T1b) or other non-invasive lesion that, as per Investigator's judgement, is considered cured with minimal risk of recurrence over the next 3 years.
• Radiation therapy within 14 days before study treatment initiation.
• Plasmapheresis within 28 days before study treatment initiation.
• Exhibiting clinical signs of meningeal or central nervous system involvement by PCL.
• Patients with peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.
• Concurrent systemic amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and/or skin changes), active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease, and any other medical condition/disease that is likely to interfere with the study procedures or results, or that in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second \[FEV1\] \<50% of predicted normal.
• Known moderate or severe persistent asthma within the past 2 years, or the patient currently has uncontrolled asthma of any classification.
• Any of the following:
• Known seropositivity for human immunodeficiency virus
• Seropositivity for hepatitis B virus defined by a positive test for hepatitis B surface antigen.
• Known seropositivity for hepatitis C virus defined by anti-HCV antibody positive or HCV-RNA quantitation positive.

Sponsors & Collaborators

• Hellenic Society of Hematology: lead

Study Sites (7)

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

Athens, Attica, Greece

RECRUITING

Hematology Clinic, General Hospital of Athens &#34;Evanggelismos&#34;

Athens, Attica, Greece

RECRUITING

Hematology Department &#34;Alexandra&#34; General Hospital of Athens

Athens, Attica, Greece

RECRUITING

Hematology Department, University General Hospital of Alexandroupolis

Alexandroupoli, Evros, Greece

RECRUITING

Hematology Department, Regional General Hospital for Cancer Treatment &#34;Metaxa&#34; of Piraeus

Piraeus, Greece

RECRUITING

Hematology Department, General Hospital of Thessaloniki &#34;Papanikolaou&#34;

Thessaloniki, Greece

RECRUITING

Hematology Department, Theageneion Cancer Hospital

Thessaloniki, Greece

RECRUITING

MeSH Terms

Interventions

daratumumab

Central Study Contacts

Eirini Katodritou, Dr

CONTACT

+302313301173; eirinikatodritou@gmail.com

Marina Stogianni

CONTACT

0030 2107211806; info@eae.gr

Study Design

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

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

Study Record Dates

• First Submitted: September 9, 2024
• First Posted: October 10, 2024
• Study Start: November 19, 2021
• Primary Completion (Estimated): January 5, 2029
• Study Completion (Estimated): January 5, 2029
• Last Updated: October 10, 2024

Record last verified: 2024-10

Locations

GR (7)