Daratumumab With DCEP for Multiple Myeloma With Plasmacytoma (Dara_DCEP)

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

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

Study Overview

• Status: Unknown
• Conditions: Plasmacytoma; Multiple Myeloma in Relapse; Daratumumab
• Intervention / Treatment: Drug: Drug Combinations

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.

• Study Type: Interventional
• Enrollment (Anticipated): 33
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: YOO MI HWANG, CRN; Phone Number: 821091186121; Email: hym1530@gmail.com
• Study Contact Backup: Name: HEE RYEONG JANG, MD; Phone Number: 821077997052; Email: wopower@naver.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
    • Contact: YOOMI HWANG, CRN; Phone Number: 821091186121; Email: hym1530@gmail.com
    • Contact: HEERYEONG JANG, MD., PhD; Phone Number: 821077997052; Email: wopower@naver.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental arm; Daratumumab plus DCEP,combination therapy is administered total of three cycles,every 4weeks(28 days). Daratumuamb 16mg/kg body weight in 500mL (the first dose,16mg/kg body weight in 1000mL) Weeks 1 to 8: weekly Weeks 9-24 : every 2 weeks if ASCT ineligible or PR but Plasmacytoma response <CR: every 2 weeks for 12weeks and then every 4 weeks for 8weeks (Total of 8 times, additional administration of daratumumab) if ASCT eligible: From 6 to 12 weeks after ASCT, administration of daratumumab is initiated within 12 weeks of ASCT and twice a month for 12 weeks and then every a months for 8 weeks. (Total of 8 additional administration of daratumumab after ASCT); dexamethasone :40mg/day D1-4, intravenous; cyclophosphamide: 400mg/m2 D1-4, intravenous; etoposide: 40mg/m2 D1-4, intravenous; cisplatin : 7mg/m2 D1-4, intravenous Pegteograstim: 6mg once, SC on day 5 or 6 of each 28-day cycle

Drug: Drug Combinations; Daratumumab plus DCEP,combination therapy is administered total of three cycles,every 4weeks(28 days). Daratumuamb 16mg/kg body weight in 500mL (the first dose,16mg/kg body weight in 1000mL) Weeks 1 to 8: weekly Weeks 9-24 : every 2 weeks if ASCT ineligible or PR but Plasmacytoma response; dexamethasone :40mg/day D1-4, intravenous; cyclophosphamide: 400mg/m2 D1-4, intravenous; etoposide: 40mg/m2 D1-4, intravenous; cisplatin : 7mg/m2 D1-4, intravenous Pegteograstim: 6mg once, SC on day 5 or 6 of each 28-day cycle; Other Names: Daratumumab plus DCEP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate in terms of plasmacytoma	disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow	within 4 weeks after the 3 cycles of combination therapy (daratumumab plus DCEP)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate (Complete response + Partial Response) by IMWG criteria	Complete response rate in terms of plasmacytoma plus partial response rate by IMWG criteria	within 4 weeks after the 3 cycles of combination therapy (daratumumab plus DCEP)
CR rate by IMWG criteria	Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow	within 4 weeks after the 3 cycles of combination therapy (daratumumab plus DCEP)
Progression free survival	from the last administration date of daratumumab to the date of disease progression or date from any cause	3,6,12,24 months after the last administration of daratumuamb
Overall Survival	from the last administration date of daratumumab to death from any cause	3,6,12,24 months after the last administration of daratumuamb
Safety and toxicity profile	according to CTCAE version 4.03	3,6,12,24 months the first administration of daratumumab

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: YOUNGIL KOH, MD., Ph.D, Seoul National University Hospital; Study Director: JEONGOK LEE, MD., Ph.D., Seoul National University Bundang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2019
• Primary Completion (Anticipated): December 21, 2019
• Study Completion (Anticipated): September 30, 2021

Study Registration Dates

• First Submitted: August 21, 2019
• First Submitted That Met QC Criteria: August 21, 2019
• First Posted (Actual): August 22, 2019

Study Record Updates

• Last Update Posted (Actual): August 22, 2019
• Last Update Submitted That Met QC Criteria: August 21, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Antineoplastic Agents; Daratumumab
• Other Study ID Numbers: 1803-019-927

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD regarding participant demographics, study treatment, response, survival, and adverse events will be shared after publishment of the study results.

IPD Sharing Time Frame

Time Frame:

IPD will be shared after the publication of the study results without time limit.

• IPD Sharing Access Criteria: IPD will be shared only for the research purpose.
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes