Daratumumab With DCEP for Multiple Myeloma With Plasmacytoma

NCT ID: NCT04065308

Last Updated: 2019-08-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-14
• Study Completion Date: 2021-09-30

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.

Conditions

Multiple Myeloma in Relapse; Plasmacytoma; Daratumumab

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

1. dexamethasone :40mg/day D1-4, intravenous

2. cyclophosphamide: 400mg/m2 D1-4, intravenous

3. etoposide: 40mg/m2 D1-4, intravenous

4. cisplatin : 7mg/m2 D1-4, intravenous Pegteograstim: 6mg once, SC on day 5 or 6 of each 28-day cycle

Group Type: EXPERIMENTAL

Drug Combinations

Intervention Type: DRUG

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)

1. dexamethasone :40mg/day D1-4, intravenous

2. cyclophosphamide: 400mg/m2 D1-4, intravenous

3. etoposide: 40mg/m2 D1-4, intravenous

4. cisplatin : 7mg/m2 D1-4, intravenous Pegteograstim: 6mg once, SC on day 5 or 6 of each 28-day cycle

Interventions

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 <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)

1. dexamethasone :40mg/day D1-4, intravenous

2. cyclophosphamide: 400mg/m2 D1-4, intravenous

3. etoposide: 40mg/m2 D1-4, intravenous

4. cisplatin : 7mg/m2 D1-4, intravenous Pegteograstim: 6mg once, SC on day 5 or 6 of each 28-day cycle

Intervention Type: DRUG

Other Intervention Names

Daratumumab plus DCEP

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

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seoul National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Youngil Koh

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

YOUNGIL KOH, MD., Ph.D

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital

JEONGOK LEE, MD., Ph.D.

Role: STUDY_DIRECTOR

Seoul National University Bundang Hospital

Locations

Seoul National University Hospital

Seoul, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

YOO MI HWANG, CRN

Role: CONTACT

hym1530@gmail.com

821091186121

HEE RYEONG JANG, MD

Role: CONTACT

wopower@naver.com

821077997052

Facility Contacts

YOOMI HWANG, CRN

Role: primary

hym1530@gmail.com

821091186121

HEERYEONG JANG, MD., PhD

Role: backup

wopower@naver.com

821077997052

Other Identifiers

1803-019-927

Identifier Type: -

Identifier Source: org_study_id