Anlotinib Hydrochloride Capsule Monotherapy and Combination Therapy Relapsed and Refractory Multiple Myeloma

Overview

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.

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.

Eligibility

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 :

1. 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.
2. 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.
        Exclusion Criteria:
          1. Asymptomatic ( smoking ) multiple myeloma.
          2. Plasma cell leukemia.
          3. Clarify the combined amyloidosis.
          4. Multiple myeloma with central nervous system ( CNS ) invasion.
          5. Pregnancy or lactation.
          6. First study before medication A. Receiving chemotherapy within 1 week. b. received
             radiotherapy or immunotherapy within 4 weeks. c. Radioimmunotherapy within 6 weeks.
          7. Transplant rejection ( after allogeneic stem cell transplantation ).
          8. Life expectancy < 4 months.
          9. Oversized surgery within 4 weeks before first study medication.
         10. Patients with unstable or active cardiovascular diseases, in line with any of the
             following :
               1. Symptomatic myocardial ischemia ;
               2. Uncontrolled and clinically significant conduction abnormalities ( e.g.,
                  exclusion of patients with ventricular arrhythmias controlled by antiarrhythmic
                  drugs ; patients with 1 degree atrioventricular ( AV ) block or asymptomatic left
                  anterior bundle branch block / right bundle branch block ( LAFB / RBBB ) were not
                  excluded.
               3. New York Heart Association ( NYHA ) definition of congestive heart failure ( CHF
                  ) classification ≥ 3 ;
               4. Acute myocardial infarction ( AMI ) occurred within 3 months before the first
                  study.
         11. Poorly controlled hypertension ( persistent systolic > 140 mmHg or diastolic > 90 mmHg
             ).
         12. In the first study, there were active infections that were not effectively controlled
             by drugs within 1 week before treatment.
         13. Known HIV positive.
         14. A, B, C hepatitis infection active period or known HCV RNA or HBsAg ( HBV surface
             antigen ) positive.
             Note : Including HBsAg negative but hepatitis B core ( HBc ) antibody positive, and
             detectable levels of hepatitis B virus deoxyribonucleic acid ( HBV-DNA ) ( HBV-DNA >
             500 IU / ml ).
         15. In the 5-year period before the first study, there were previous malignant tumors that
             needed treatment or had evidence of recurrence [ except for skin basal cell carcinoma
             and the following carcinoma in situ : squamous cell carcinoma, bladder carcinoma in
             situ, endometrial carcinoma in situ, cervical carcinoma in situ / atypical
             hyperplasia, incidental histological findings of prostate cancer ( TNM stage T1a or
             T1b ) or breast carcinoma in situ ].
         16. There is dysphagia or active gastrointestinal ( GI ) dysfunction that may affect drug
             absorption.
         17. There were ≥ grade 3 peripheral neuropathy and ≥ grade 2 painful neuropathy within 3
             weeks before the first study.
         18. Active mental disorders or organic diseases considered by researchers to be unsuitable
             for inclusion.
         19. Participated in clinical trials of other drugs within three weeks or five drug
             half-lives ( T1 / 2 ) prior to the first study.
         20. Before treatment received the following treatment, in line with any of the following :
               1. Platelet transfusion within 1 week before the first study ;
               2. infusion of red blood cells ( RBC ) within 2 weeks before the first study ;
               3. The following blood growth factors were used within 2 weeks prior to the first
                  study : granulocyte colony-stimulating factor ( G-CSF ), granulocyte-macrophage
                  colony-stimulating factor ( GM-CSF ), erythropoietin ( EPO ), megakaryocyte
                  growth factor, and / or platelet-stimulating factor.
         21. Intolerance or contraindications to glucocorticoid therapy are known.
         22. Anlotinib has been used.