UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000010470 |
|---|---|
| Receipt number | R000012171 |
| Scientific Title | Evaluation of the Feasible dose of Lenalidomide as maintenance therapy after Allogeneic hematopoietic stem cell Transplantation for multiple myeloma |
| Date of disclosure of the study information | 2013/04/11 |
| Last modified on | 2026/04/27 14:42:43 |
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Basic information
Public title
Evaluation of the Feasible dose of Lenalidomide as maintenance therapy after Allogeneic hematopoietic stem cell Transplantation for multiple myeloma
Acronym
E-FLAT study
Scientific Title
Evaluation of the Feasible dose of Lenalidomide as maintenance therapy after Allogeneic hematopoietic stem cell Transplantation for multiple myeloma
Scientific Title:Acronym
E-FLAT study
Region
| Japan |
Condition
Condition
multiple myeloma (including plasma cell leukemia)
Classification by specialty
| Hematology and clinical oncology |
Classification by malignancy
Malignancy
Genomic information
NO
Objectives
Narrative objectives1
The study will be conducted to evaluate the safety and efficacy of lenalidomide as maintenance therapy after allogeneic hematopoietic stem cell transplantation for multiple myeloma.
Basic objectives2
Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Exploratory
Trial characteristics_2
Explanatory
Developmental phase
Phase I,II
Assessment
Primary outcomes
Phase I: dose limiting toxicity and maximum tolerated dose
Phase II: the rate of improvement of remission status after 4 cycles lenalidomide maintenance therapy
Key secondary outcomes
1) adverse event frequencies
2) acute and chronic GVHD
3) a continuous administration period
4) 1-year overall survival after transplantation
5) 1-year progression-free survival after transplantation
6) T,NK-cells recovery and activation status
Base
Study type
Interventional
Study design
Basic design
Single arm
Randomization
Non-randomized
Randomization unit
Blinding
Open -no one is blinded
Control
Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment
Intervention
No. of arms
1
Purpose of intervention
Treatment
Type of intervention
| Medicine |
Interventions/Control_1
Lenalidomide maintenance therapy starts between 100 and 365 days after allogeneic stem cell transplantation. Three dose-levels (5 mg/every other day, 5 mg/day, 10 mg/day) will be investigated. Within each level lenalidomide will be given for 21 days followed by 1 week rest. Overall 4 cycles will be planned for each patient and a minimum number of 3 patients will be supposed to be treated at each dose level. This study will start with 5 mg/day. If no dose limiting toxicity (DLT) will be observed in 3 patients during first 2 cycles the following 3 patients will be treated with the next higher dose. If one of the 3 patients will experience DLT at the current dose, 3 more patients will be treated at the same dose level. If none of these 3 additional patients will experience DLT, the dose will be escalated in subsequent patients to the next dose level. If one of these 3 patients will experience DLT, the next lower dose level will be defined as the maximal tolerated dose (MTD). If 2 or more of 3 patients or 2 or more of 6 patients in the same dose level will experience DLT, then previous lower dose will be declared as the MTD. The study will be filled up with additional patients for up to a total number of 17 patients who use the MTD.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10
Eligibility
Age-lower limit
| 18 | years-old | <= |
Age-upper limit
| 65 | years-old | >= |
Gender
Male and Female
Key inclusion criteria
(1) Patients with symptomatic multiple myeloma (including plasma cell leukemia), and more than 100 days after allogeneic hematopoietic stem cell transplantation
(2) Regardless of the period from diagnosis to maintenance therapy, pretreatment, conditioning regimen, and graft source
(3) Age at agreement acquisition between 18 and 65 years old
(4) ECOG performance status being 0 or 1
(5) Patients who have the following laboratory values 14 days before enrollment
1. SpO2 >= 94%
2. Creatinine clearance >= 30 ml/min
3. Total bilirubin <= 2 mg/dl
4. AST and ALT <= 3 x upper limit of normal
5. Normal electrocardiogram
6. Ejection fraction >= 45%
(6) The agreement in the document obtained from the person himself about participation in this study (Parental consent is required if patients are < 20 yaers old.)
Key exclusion criteria
(1) Patients with poorly controlled in spite of the continuous use of insulin
(2) Patients with poorly controlled hypertension
(3) Patients with poorly controlled active infection
(4) Patients with coexistence of malignancy
(5) Patients who are or may be pregnant or are nursing
(6) Patients with serious mental disorder
(7) Patients with HBs antigen or HBe antigen positive
(8) Patients with HIV antibody positive
(9) Patients who are allergic to lenalidomide or thalidomide
(10) Patients with active acute or chronic GVHD
(11) Patients with platelet count < 30,000/uL or neutrophil count < 1,000/uL
Target sample size
23
Research contact person
Name of lead principal investigator
| 1st name | Yoshinobu |
| Middle name | |
| Last name | Kanda |
Organization
Saitama Medical Center, Jichi Medical University
Division name
Division of Hematology
Zip code
330-8503
Address
1-847, Amanuma-cho, Omiya-ku, Saitama-shi, Saitama
TEL
048-647-2111
ycanda-tky@umin.ac.jp
Public contact
Name of contact person
| 1st name | Shun-ichi |
| Middle name | |
| Last name | Kimura |
Organization
Saitama Medical Center, Jichi Medical University
Division name
Division of Hematology
Zip code
330-8503
Address
1-847, Amanuma-cho, Omiya-ku, Saitama-shi, Saitama
TEL
048-647-2111
Homepage URL
skimura@jichi.ac.jp
Sponsor or person
Institute
Division of Hematology, Saitama Medical Center, Jichi Medical University
Institute
Department
Personal name
Funding Source
Organization
Div. Hematol, Saitama Medical Center, Jichi Medical Univ.
This research fund is in part supported by the donation from Celgene Co., Ltd., etc.
Organization
Division
Category of Funding Organization
Other
Nationality of Funding Organization
Other related organizations
Co-sponsor
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Saitama Medical Center, Jichi Medical University
Address
1-847, Amanuma-cho, Omiya-ku, Saitama-city, Saitam
Tel
0486472111
rinri@jichi.ac.jp
Secondary IDs
Secondary IDs
NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
Institutions
Other administrative information
Date of disclosure of the study information
| 2013 | Year | 04 | Month | 11 | Day |
Related information
URL releasing protocol
https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000012171&t
Publication of results
Published
Result
URL related to results and publications
https://onlinelibrary.wiley.com/doi/10.1002/hon.70129
Number of participants that the trial has enrolled
9
Results
The study included 10 patients; one was excluded due to early disease progression, leaving nine patients evaluable for toxicity. The phase II portion was not conducted due to expiration of the trial period. The median interval from allo-HCT to initiation of lenalidomide was 244 days (range, 169-330 days). At the 10 mg/day dose level, one patient experienced moderate chronic GVHD meeting the predefined criteria for DLT. No other DLTs occurred, establishing the MTD at 10 mg/day.
Results date posted
| 2026 | Year | 04 | Month | 27 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
The eligibility criteria were as follows: (1) patients with symptomatic multiple myeloma, including primary plasma cell leukemia (pPCL), who had survived at least 100 days after allo-HCT; (2) age between 18 and 65 years; (3) Eastern Cooperative Oncology Group Performance Status of 0 or 1; (4) the following laboratory criteria: SpO2 >= 94%, creatinine clearance >= 30 ml/min, total bilirubin <= 2 mg/dl, aspartate aminotransferase and alanine aminotransferase <= 3 times the upper limit of normal, normal electrocardiogram, and ejection fraction >= 45%.
The main exclusion criteria were as follows: (1) poorly controlled diabetes mellitus; (2) poorly controlled hypertension; (3) active infection; (4) coexisting malignancy; (5) pregnant or nursing female; (6) serious mental disorder; (7) positive for HBs antigen or HBe antigen; (8) HIV antibody positive; (9) allergic to lenalidomide or thalidomide; (10) active acute or chronic GVHD; (11) platelet count < 3 x 10^4 cells/mm3 or neutrophil count < 1000 cells/mm3.
Participant flow
Lenalidomide maintenance therapy was initiated between 100 and 365 days after allo-HCT. According to the Fibonacci design, three dose-levels (5 mg every other day, 5 mg/day, and 10 mg/day) were investigated in the phase I study (Figure 1). Lenalidomide was administered on day 1 to 21 of a 28-day cycle for at least four cycles. The starting dose was 5 mg/day, and maximum dose was set at 10 mg/day based on the results of the previous studies. DLT was evaluated after the first two cycles, and thereafter, the dose could be escalated by one level at the discretion of the attending physician. After the MTD was determined, phase II study was planned with a target enrollment of 17 patients receiving the MTD of lenalidomide.
Adverse events
No cases of acute GVHD were observed, but chronic GVHD occurred in three patients. One patient with moderate chronic GVHD involving the oral mucosa and skin gradually improved about 3 months after lenalidomide was discontinued and the tacrolimus dose was increased again. The other two patients with mild chronic GVHD experienced spontaneous resolution without additional treatment. No grade >= 3 non-hematologic adverse events were reported. In the first cycle, one case of grade 1 liver dysfunction was documented, which resolved with observation alone and did not lead to treatment discontinuation. Additionally, five patients had experienced hematologic toxicity of any grade by Cycle 4. Grade 3 hematologic toxicities included anemia in one patient and thrombocytopenia in two patients. One patient required a red blood cell transfusion, but no patient discontinued lenalidomide maintenance therapy due to hematologic toxicity.
Outcome measures
Phase I employed an open-label, dose escalation design to determine the MTD and to evaluate the DLT of lenalidomide as maintenance therapy after allo-HCT in patients with multiple myeloma.
In the phase II study, we planned to evaluate the rate of improvement in remission status after four cycles of lenalidomide maintenance therapy in an open-label, uncontrolled design, using the MTD determined in the phase I study. Additionally, we planned to assess the frequency of adverse events, the incidence of acute and chronic GVHD, the duration of continued treatment, OS, progression-free survival (PFS), and T and NK cell activation status after lenalidomide maintenance therapy.
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Completed
Date of protocol fixation
| 2013 | Year | 04 | Month | 11 | Day |
Date of IRB
| 2013 | Year | 04 | Month | 11 | Day |
Anticipated trial start date
| 2013 | Year | 05 | Month | 01 | Day |
Last follow-up date
| 2020 | Year | 10 | Month | 31 | Day |
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
Other
Other related information
Management information
Registered date
| 2013 | Year | 04 | Month | 11 | Day |
Last modified on
| 2026 | Year | 04 | Month | 27 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000012171
