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Daratumumab With DCEP for Multiple Myeloma With Plasmacytoma (Dara_DCEP)

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ClinicalTrials.gov Identifier: NCT04065308
Recruitment Status : Recruiting
First Posted : August 22, 2019
Last Update Posted : August 22, 2019
Sponsor:
Information provided by (Responsible Party):
Youngil Koh, Seoul National University Hospital

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

Condition or disease Intervention/treatment Phase
Multiple Myeloma in Relapse Plasmacytoma Daratumumab Drug: Drug Combinations Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 14, 2019
Estimated Primary Completion Date : December 21, 2019
Estimated Study Completion Date : September 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Daratumumab

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)

  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
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 <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
Other Name: Daratumumab plus DCEP




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


Secondary Outcome Measures :
  1. Response rate (Complete response + Partial Response) by IMWG criteria [ Time Frame: within 4 weeks after the 3 cycles of combination therapy (daratumumab plus DCEP) ]
    Complete response rate in terms of plasmacytoma plus partial response rate by IMWG criteria

  2. CR rate by IMWG criteria [ Time Frame: within 4 weeks after the 3 cycles of combination therapy (daratumumab plus DCEP) ]
    Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow

  3. Progression free survival [ Time Frame: 3,6,12,24 months after the last administration of daratumuamb ]
    from the last administration date of daratumumab to the date of disease progression or date from any cause

  4. Overall Survival [ Time Frame: 3,6,12,24 months after the last administration of daratumuamb ]
    from the last administration date of daratumumab to death from any cause

  5. Safety and toxicity profile [ Time Frame: 3,6,12,24 months the first administration of daratumumab ]
    according to CTCAE version 4.03



Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04065308


Contacts
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Contact: YOO MI HWANG, CRN 821091186121 hym1530@gmail.com
Contact: HEE RYEONG JANG, MD 821077997052 wopower@naver.com

Locations
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Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of
Contact: YOOMI HWANG, CRN    821091186121    hym1530@gmail.com   
Contact: HEERYEONG JANG, MD., PhD    821077997052    wopower@naver.com   
Sponsors and Collaborators
Seoul National University Hospital
Investigators
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Principal Investigator: YOUNGIL KOH, MD., Ph.D Seoul National University Hospital
Study Director: JEONGOK LEE, MD., Ph.D. Seoul National University Bundang Hospital

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Responsible Party: Youngil Koh, Assistant Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT04065308     History of Changes
Other Study ID Numbers: 1803-019-927
First Posted: August 22, 2019    Key Record Dates
Last Update Posted: August 22, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD regarding participant demographics, study treatment, response, survival, and adverse events will be shared after publishment of the study results.
Supporting Materials: Study Protocol
Time Frame:

Time Frame:

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

Access Criteria: IPD will be shared only for the research purpose.

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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
Additional relevant MeSH terms:
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Multiple Myeloma
Daratumumab
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs