Multiple Myeloma
Conditions
Brief summary
This is a Single-center, Open-label, Single-arm Exploratory Clinical Study to evaluate the safety and efficacy of Anlotinib Hydrochloride Capsule Monotherapy and Combination Therapy in relapsed or refractory multiple myeloma patient.
Detailed description
This study is an exploratory study, which is divided into two parts. The first part uses BOIN design to explore the phase II recommended dose and safety of anlotinib monotherapy or combination regimen. The second part explored the efficacy and safety of anlotinib in the treatment of RRMM with phase II recommended dose monotherapy and combination regimen. Set up two treatment options, in which A program for monotherapy : Anlotinib monotherapy + dexamethasone ; regimen B is a combination therapy regimen : anlotinib combined with pomalidomide or dalattoumab + dexamethasone.
Interventions
Anlotinib hydrochloride is a muti-target tyrosine kinase inhibitor.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. known and volunteered to sign the Informed Consent; 2. Age≥ 18 years 3. Patients must have previously received a regimen containing immunomodulators and protease inhibitors, and the end-line treatment regimen is refractory or intolerant ( patients recorded as intolerant must discuss and obtain permission from the sponsor 's medical inspector before entering the screening ). Refractory includes primary refractory ( patients did not achieve minimal remission MR or disease progression during treatment ) or secondary refractory ( patients developed disease progression within 60 days after treatment ). 4. Non-hematological toxicity associated with previous treatment occurring prior to the first use of the drug must be reduced to ≤ grade 2, except for peripheral neuropathy, which is specified in article 17 of the
Exclusion criteria
. 5. Liver function met the following criteria : total bilirubin \< 2 × upper limit of normal range ( ULN ) ( for patients with Gilbert syndrome, total bilirubin \< 3 × ULN ), AST \< 2.5 × ULN and ALT \< 2.5 × ULN. 6. Renal function meets the following criteria : creatinine clearance ≥ 20 mL / min ( Cockroft-Gault formula ). 7. The ECOG performance status score is 0, 1 or 2. 8. With measurable multiple myeloma, at least one of the following needs to be met : 1. Serum M protein ( SPEP ) ≥ 5 g / L. 2. 24 hour urinary M protein excretion rate ≥ 0.2g ( 200mg ). 3. Serum free light chain ( sFLC ) ≥ 100 mg / L and abnormal free light chain ratio. 9. Blood routine examination met the following criteria ( platelet transfusion was not received within 1 week before the first study, and red blood cell transfusion was not received within 2 weeks before the first study ) : 1. Hemoglobin level ≥ 80g / L. 2. Absolute neutrophil count ( ANC ) ≥ 1000 / mm3 ( 1.0x109 / L ). 3. If the proportion of plasma cells in bone marrow \< 50 %, platelet count ≥ 75,000 / mm3 ( 75x109 / L ) ; such as bone marrow plasma cell ratio ≥ 50 %, platelet count ≥ 50,000 / mm3 ( 50x109 / L ). 10.10.Possible pregnant women must meet the following two conditions : a. Agrees to use both contraceptive methods approved by the research physician or complete abstinence during the use of the research drug and within three months after the last administration of the research drug from the date of signing the informed consent. i. Abstinence : Acceptable when this method is consistent with the preferred and daily lifestyle of the subject. Periodic abstinence ( such as according to the calendar, ovulation, symptoms of body temperature, after ovulation method ) is not accepted. ii. acceptable contraceptive methods include : oral contraceptives, injectable contraceptives or implantable hormonal contraceptives ; intrauterine device ; barrier contraceptive tools with spermicide ; or the partner received sterilization, combined with the use of at least one barrier contraceptive. b. screening serum pregnancy test results were negative. Note : Fertility refers to all women who have begun their menstrual period, are not in the post-menopausal period and have not undergone surgical sterilization ( e.g. hysterectomy, bilateral tubal ligation, bilateral ovariectomy ). Postmenopause refers to amenorrhea for more than 12 consecutive months for non-specific reasons. Women who are using mechanical contraceptive methods such as oral contraceptives or intrauterine devices should be considered to have fertility. 11\. Male subjects ( including those who have undergone vasectomy ) must consent to the use of condoms in their sexual life with women of childbearing age and, from the date of signing the informed consent form, have no plans to conceive a woman during the use of the study drug and within three months after the last administration of the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate ( ORR ) | From date of randomization until the date of first documented progression,assessed up to 100 months | partial remission ( PR ) + very good partial remission ( VGPR ) + complete remission ( CR ) + strict complete remission ( sCR ). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TTP | From date of randomization until the date of death from any cause,assessed up to 100 months | Duration from treatment initiation to disease progression |
| PFS | From date of randomization until the date of death from any cause,assessed up to 100 months | Time from the start of treatment to disease progression or death from any cause |
| DOR | From date of randomization until the date of death from any cause,assessed up to 100 months | Duration from first observation of at least partial remission ( PR ) to disease progression or death from disease progression, whichever comes first |
| CBR | From date of randomization until the date of death from any cause,assessed up to 100 months | ORR + Minimal Remission ( MR ) |
| 6 months, 9 months, 12 months survival rate ( SR ) | 6 months, 9 months, 12 months | 6 months, 9 months, 12 months survival rate |
| OS | From date of randomization until the date of death from any cause,assessed up to 100 months | Time from initiation of treatment to death from any cause |
| MRD in CR and sCR patients MRD in CR and sCR patients | through study completion, an average of 1 year | Minimal residual disease ( MRD ) in patients with CR or sCR |
| The influence of risk factors stratification based on fluorescence in situ hybridization ( FISH ) on clinical efficacy, including del 13, del 17p13, t ( 4 ; 14 ), t ( 14 ; 16 ), 1q21 amplification | 28 days | FISH analysis to diagnose and determine MM subtypes |
| security of medical | From date of randomization until the date of first documented progression,assessed up to 100 months | Including hematological toxicity and non-hematological toxicity ; neutropenia, thrombocytopenia, anemia and hand-foot skin reaction, hypertension, hypertriglyceridemia, proteinuria, diarrhea, fatigue, hemoptysis, hypothyroidism, hyponatremia, etc. |
| Clinical Benefit Rate ( CBR ) + Stable Disease DCR | 12 weeks | clinical benefit rate ( CBR ) + stable disease ( SD : at least 12 weeks ) |
Countries
China
Contacts
Primary ContactGang An
Outcome results
None listed