A multicenter phase II study to evaluate the efficacy and safety of fixed-duration sequential treatment combined with novel agents and autologous stem cell transplantation for newly diagnosed elderly multiple myeloma. -JSCT EMM21-

JRCT ID: jRCTs071210084

Registered date:26/10/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Multiple myeloma
• Date of first enrollment: 26/10/2021
• Target sample size: 75
• Study type: Interventional

Intervention(s)

1. Daratumumab + lenalidomide + dexamethasone combination induction therapy (DRD therapy)
DRD 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. Autologous peripheral blood stem cell collection (PBSCH) with G-CSF + prelixaform combination
G-CSF 10 ug / kg day1-5 + plerixafor 0.24 mg / kg day4 + PBSCH
3. Pre-transplant treatment with high-dose melphalan therapy and autologous peripheral blood stem cell transplantation (PBSCT)
Mel 70mg / m2 day-3,-2 + PBSCT day0
4. Ixazomib maintenance therapy
Ixazomib maintenance therapy 1-4 courses: Izazomib 3 mg / body day 1,8,15
Ixazomib maintenance therapy 5-26th course: Izazomib 4mg / body day1,8,15 if tolerated during cycles 1-4.

Outcome(s)

• Primary Outcome: 2-year progression-free survival rate (PFS)

Secondary Outcome

1) Rate of response after induction therapy
2) Response rate after autologous peripheral blood stem cell transplantation
3) Response rate 1 year, 2 years, and 3 years after the start of maintenance therapy
4) Overall survival rate after induction therapy, autologous peripheral blood stem cell transplantation, and maintenance therapy 1 year, 2 years, and 3 years
5) QOL after induction therapy, autologous peripheral blood stem cell transplantation, maintenance therapy 1 year, 2 years, 3 years
6) Frequency of adverse events
7) Percentage of FCM-MRD negative 1 year, 2 years, and 3 years after the start of maintenance therapy after induction therapy, autologous peripheral blood stem cell transplantation,
8) Percentage of immunophenotypic CR 1 year, 2 years, and 3 years after the start of maintenance therapy after induction therapy, autologous peripheral blood stem cell transplantation
9) Rate of progression-free survival 1 year, 2 years, and 3 years after the start of ixazomib maintenance therapy
10) Overall survival rate 1 year, 2 years, and 3 years after the start of ixazomib maintenance therapy
11) Changes in non-neoplastic immunoglobulin levels 1 year, 2 years, and 3 years after induction therapy and autologous peripheral blood stem cell transplantation
12) Autologous peripheral blood stem cell collection completion rate, collection amount, collection days
13) Number of peripheral blood CD34-positive cells on the day of autologous peripheral blood stem cell collection
14) Association of autologous peripheral blood stem cell collection products with FCM-MRD, PFS, and response
15) Research treatment completion rate
16) Evaluation of genomic abnormality search at the time of initial onset, exacerbation, and recurrence
17) Discontinuation / dropout rate due to adverse events during induction therapy
18) Comparison of simple fraility scoring and IMWG fraility scoring

Key inclusion & exclusion criteria

• Age minimum: >= 66age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

1) Patients who are 66 years old or older and 75 years old or younger at the time of registration and fit.
2) Cases of multiple myeloma that meet the diagnostic criteria of IMWG (revised in 2014).
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 free light chain concentration ratio is abnormal in the serum free light chain measurement.
Serum M protein is 1g / dL or more
Urinary M protein is 200 mg or more after 24hour urine storage
The free light chain concentration ratio in serum is abnormal and the free light chain concentration is 100 mg / L or more.
4) Cases without major organ damage.
5) Cases in which the general condition is good (ECOG Performance Status; PS is 0 to 2).
6) For female patients, contraceptive during the study period after menopause (patients who have passed more than one year since the last menstrual period) or by observing RevMate and using surgical contraception or appropriate methods (contraceptives, contraceptives, etc.) I have agreed to do so. For male patients, we adhere to RevMate and agree to use appropriate contraception during the study.
7) Patients who have been notified have received sufficient explanation from the doctor in charge about the contents of this study using explanatory documents, and have voluntarily agreed to participate in this study in writing.

Exclude criteria

1) Cases of smoldering and IgM myeloma, solitary plasmacytoma, plasmacytotic leukemia, POEMS syndrome, and Waldenstrom macroglobulinemia.
2) Cases with symptoms due to amyloidosis and histologically proven amyloid deposits
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) Patients with central nervous system infiltration of myeloma cells.
6) HIV antibody positive, HBs antigen positive, HCV-PCR positive (HCV-PCR negative patients are possible).
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 doctor in charge judged to be inappropriate.

Related Information

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