Clinical trial NCT04065308: Daratumumab With DCEP for Multiple Myeloma With Plasmacytoma
Official title: A Phase II Trial to Evaluate the Efficacy of Daratumumab With DCEP in Multiply Myeloma Patients With Plasmacytoma Who Fail to Achieve Complete Remission With Bortezomib Containing Induction Regimen
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Multiple Myeloma in Relapse
Plasmacytoma
Daratumumab
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2019-08-22
Enrollment: 33
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial aimed to investigate the therapeutic efficacy of daratumumnab plus chemitherapy in multiple myeloma with plasmacytoma.

Detailed description: Multiple myeloma with plasmacytoma is a disease with significantly short overall survival. Cancer cells in plasmacytoma has inferior response compared to cancer cells in bone marrow in multiple myeloma. It is revealed that genetic difference such as CCND1 overexpression and RAS mutation exists between plasmacytoma and intramedullary plasma cell myeloma, implying different treatment strategy should be applied to overcome poor prognosis of this distinct disorder.

Even in the era of potent IMiDs and proteasome inhibitors, median overall survival of multiple myeloma patients with plasmacytoma is less than 5 years. Moreover, relapse in a form of soft tissue plasmacytoma is frequently observed after triplet combination treatment in multiple myeloma. Hence, multiple myeloma with plasmacytoma is a disease where unmet medical need still exists.

Biologically, plasmacytoma is characterized by high plasma cell proliferation, angiogenesis gene profile, and adhesion molecule changes mimicking solid tumor . Responsiveness to chemotherapy used in myeloma including IMIds5 and proteasome inhibitor6 is obtuse in plasmacytoma. Only small fraction of young patients receiving high-dose chemotherapy followed by autologous stem cell transplantation may overcome adverse prognostic impact of plasmacytomas . Even it is recommended that VTD-PACE would be used as the first line treatment for plasmacytomas.

In summary, cancer cells in plasmacytoma bear biologic characteristics of solid tumor cells and do respond to high-dose chemotherapy. And this phenomenon is very similar to lymphoma for the following reasons. Like lymphoma, 1) plasmacytoma express tumor antigen strongly (CD38 or CD138), 2) they form a solid mass, and 3) respond to cytotoxic chemotherapy in a dose-response manner.

Considering the success story of rituximab in lymphoma, we conjecture that daratumumab may work excellently to control plasmacytoma. Hence, we propose a treatment regimen consists of DCEP chemotherapy and daratumumab.

Eligibility criteria: Inclusion Criteria:

ECOG performance status 2 or better Adequate physical condition that could tolerate cytotoxic chemotherapy judged by investigator Relapsed/Refractory Multiple myeloma with plasmacytoma Adequate cardiac function , hepatic and renal function Adequate hematopoietic function i. White blood cells ≥3000 ii. Absolute neutrophil count ≥1500 iii. Platelets ≥50,000 iv. Hemoglobin \>7.5mg/dL ( Transfusion is not permitted within 2 weeks.) v. Total bilirubin \<1.5 times upper limit of normal vi. AST and ALT \<1.5 times upper limit of normal vii. Serum creatinine \<1.5 times upper limit of normal Singed and dated informed consent of document indicating that the patient(or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment For women of child bearing age, it should be confirmed that they are not pregnant and that they should be contraception during the study period and for up to 3 months after the end of study Male should agree to the barrier method during the study period and up to 3 months after the end of the study

Exclusion Criteria:

* HSCT (hematopoietic stem cell transplantation) within the last 12 weeks
* Other severe acute or

Primary outcomes:
measure: Complete response rate in terms of plasmacytoma
timeFrame: within 4 weeks after the 3 cycles of combination therapy (daratumumab plus DCEP)
Secondary outcomes:
measure: Response rate (Complete response + Partial Response) by IMWG criteria
timeFrame: within 4 weeks after the 3 cycles of combination therapy (daratumumab plus DCEP)
measure: CR rate by IMWG criteria
timeFrame: within 4 weeks after the 3 cycles of combination therapy (daratumumab plus DCEP)
measure: Progression free survival
timeFrame: 3,6,12,24 months after the last administration of daratumuamb
measure: Overall Survival
timeFrame: 3,6,12,24 months after the last administration of daratumuamb
measure: Safety and toxicity profile
timeFrame: 3,6,12,24 months the first administration of daratumumab
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: YOUNGIL KOH, MD., Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Bundang Hospital
name: JEONGOK LEE, MD., Ph.D.
role: STUDY_DIRECTOR
References: