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

Multiple Myeloma Clinical Trial

Official title:

Single-center, Open-label, Single-arm Exploratory Clinical Trial of Anlotinib Monotherapy and Combination Therapy in Relapsed / Refractory MM Previously Treated With Immunomodulator and Protease Inhibitor Regimens

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05549973
• Other study ID #: An-MM-001
• Status: Recruiting
• Phase: Phase 1
• Start date: September 2022
• Est. completion date: July 2024

Study information

• Verified date: September 2022
• Source: Institute of Hematology & Blood Diseases Hospital
• Contact: Gang An
• Phone: 008613502181109
• Email: angang[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: July 2024
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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 : 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.

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Anlotinib Hydrochloride Capsule
Anlotinib hydrochloride is a muti-target tyrosine kinase inhibitor.

Locations

Country	Name	City	State
China	InstituteHBDH	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate ( ORR )	partial remission ( PR ) + very good partial remission ( VGPR ) + complete remission ( CR ) + strict complete remission ( sCR ).	From date of randomization until the date of first documented progression,assessed up to 100 months
Secondary	6 months, 9 months, 12 months survival rate ( SR )	6 months, 9 months, 12 months survival rate	6 months, 9 months, 12 months
Secondary	TTP	Duration from treatment initiation to disease progression	From date of randomization until the date of death from any cause,assessed up to 100 months
Secondary	PFS	Time from the start of treatment to disease progression or death from any cause	From date of randomization until the date of death from any cause,assessed up to 100 months
Secondary	DOR	Duration from first observation of at least partial remission ( PR ) to disease progression or death from disease progression, whichever comes first	From date of randomization until the date of death from any cause,assessed up to 100 months
Secondary	CBR	ORR + Minimal Remission ( MR )	From date of randomization until the date of death from any cause,assessed up to 100 months
Secondary	Clinical Benefit Rate ( CBR ) + Stable Disease DCR	clinical benefit rate ( CBR ) + stable disease ( SD : at least 12 weeks )	12 weeks
Secondary	OS	Time from initiation of treatment to death from any cause	From date of randomization until the date of death from any cause,assessed up to 100 months
Secondary	MRD in CR and sCR patients MRD in CR and sCR patients	Minimal residual disease ( MRD ) in patients with CR or sCR	through study completion, an average of 1 year
Secondary	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	FISH analysis to diagnose and determine MM subtypes	28 days
Secondary	security of medical	Including hematological toxicity and non-hematological toxicity ; neutropenia, thrombocytopenia, anemia and hand-foot skin reaction, hypertension, hypertriglyceridemia, proteinuria, diarrhea, fatigue, hemoptysis, hypothyroidism, hyponatremia, etc.	From date of randomization until the date of first documented progression,assessed up to 100 months