Efficacy and safety of response-adapted continuous daratumumab plus lenalidomide-dexamethasone therapy in combination with autologous stem cell transplantation for newly diagnosed multiple myeloma

JRCT ID: jRCTs071210074

Registered date:05/10/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Multiple myeloma
• Date of first enrollment: 05/10/2021
• Target sample size: 172
• Study type: Interventional

Intervention(s)

1) Induction therapy
DRD therapy 1,2 course: Dara IV 16mg / kg or Dara SC 1800mg / body day1,8,15,22 + Len 25mg / body day1-21 + Dex 40mg / body day1,8,15,22
DRD therapy 3,4 course: Dara IV 16mg / kg or Dara SC 1800mg / body day1,15 + Len 25mg / body day1-21 + Dex 40mg / body day1,8,15,22
2) PBSCH
G-CSF 10 ug / kg day1-5 (or 6) + plerixafor 0.24 mg / kg day4 (or 4-5) + PBSCH
3) PBSCT
Mel 100mg / m2 day-3,-2 + PBSCT day0
4.1) Consolidation therapy (VGPR or higher after PBSCT)
DRD therapy 1,2 course: Dara IV 16mg / kg or Dara SC 1800mg / body day1,8,15,22 + Len 25mg / body or LTD day1-21 + Dex 40mg / body day1,8,15,22
DRD therapy 3,4 course: Dara IV 16mg / kg or Dara SC 1800mg / body day1,15 + Len 25mg / body or LTD day1-21 + Dex 40mg / body day1,8,15,22
4.2) Consolidation therapy (PR or less after PBSCT)
KRD 1 course: Cfz 20mg / m2 day1,2 + Cfz 27mg / m2 day8,9,15,16 + Len 25mg / body or LTD day1-21 + Dex 40mg / body day1,8,15,22
KRD 2-4 course: Cfz 27mg / m2 day1,2,8,9,15,16 + Len 25mg / body or LTD day1-21 + Dex 40mg / body day1,8,15,22
5) Maintenance therapy
Dara IV 16mg / kg or Dara SC 1800mg / body day1 + Len 10mg / body or LTD day1-21 until-PD

Outcome(s)

• Primary Outcome: Percentage of complete response (CR) or better (CR, sCR) after consolidation therapy

Secondary Outcome

1) Percentage of complete response or better (CR, sCR), percentage of VGPR or better, and percentage of ORR after induction therapy
2) Percentage of complete response or better (CR, sCR) after autologous peripheral blood stem cell transplantation, percentage of VGPR or higher, and percentage of ORR
3) Percentage of complete response or better (CR, sCR), VGPR or better, and ORR after consolidation therapy in the DRD and KRD groups
4) Percentage of complete response or higher (CR, sCR), VGPR or higher, and ORR 3 years after the start of research treatment
5) Upgrade rate to VGPR or higher after consolidation therapy in the group of patients with PR or lower after autologous transplantation
6) Discontinuation / dropout rate due to adverse events during induction therapy
7) Collection status of autologous peripheral blood stem cells (Plerixafor usage status, blood processing volume during apheresis)
8) 3-year progression-free survival rate (3-yr PFS)
9) 3-year overall survival rate (3-yr OS)
10) 3-year treatment success rate (3-yr TTF)
11) Adverse events, frequency of adverse events
12) FCM-MRD (Euro-Flow and SRL Flow) negative rate after induction therapy, autologous peripheral blood stem cell transplantation, consolidation therapy, and 1 year and 2 years after the start of maintenance therapy
13) FCM-MRD negative rate in collected stem cells
14) Relationship between FCM-MRD and PFS and OS
15) Comparison between Euro-Flow and SRL-Flow
16) Comparison between FCM-MRD (NGF-MRD) and NGS-MRD
17) Relationship between genetic abnormality profile of myeloma and treatment responsiveness
18) Relationship between bone marrow-derived DNA and cfDNA gene abnormality profile, relationship with treatment responsiveness
19) Effect of daratumumab on myeloma cells and bone marrow microenvironment including immunocompetent cells
20) Relationship between CHIP and post-transplant course, responsiveness to consolidation therapy, and frequency of secondary myeloproliferative neoplasms

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 65age old
• Gender: Both

Include criteria

1) Cases in which the age at the time of registration is 20 to 65 years.
2) Cases of untreated multiple myeloma that meet the diagnostic criteria of IMWG.
3) M protein, which is an index for determining the therapeutic effect, can be measured in serum or urine. Or, a case in which the serum FLC ratio is abnormal by FLC measurement.
4) Cases without major organ damage.
5) Cases in good general condition.
6) Survival of 3 months or more can be expected.
7) For female patients, it is agreed to use postmenopausal or surgical contraception or appropriate methods during the study period. For male patients, we have agreed to use appropriate methods of contraception during the study.
8) Written consent has been obtained for participation in this study.

Exclude criteria

1) Cases of smoldering and IgM myeloma, solitary plasmacytoma, plasmacytotic leukemia, POEMS syndrome, and Waldenstrom macroglobulinemia.
2) Cases with amyloidosis.
3) Patients who underwent surgery or radiation therapy within 14 days before registration.
4) Patients who received more than 30 mg/day in terms of prednisolone within 14 days before registration.
5) Cases in which myeloma cells infiltrate the central nervous system.
6) HIV antibody positive, HBs antigen positive, HCV antibody positive cases.
7) Cases with uncontrolled liver dysfunction, renal dysfunction, cardiac dysfunction, pulmonary dysfunction, diabetes, hypertension, and infectious diseases.
8) Active and advanced stage double cancer cases.
9) Cases with severe psychiatric disorders such as schizophrenia.
10) Pregnant women and cases who may become pregnant during the study period or are breastfeeding.
11) If the SARS-CoV2 test is found to be positive before the case registration, cases in which the symptoms have not disappeared and cases within 30 days after the positive judgment are excluded.
12) Other cases that the principal investigator or the investigator deems inappropriate.

Related Information

• Primary Sponsor: Kikushige Yoshikane
• Source(s) of Monetary Support: Kyushu University Hospital