Trial Title:
Puesta Mesylate Combined With Pomalidomide Capsules and Low-dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
NCT ID:
NCT06484829
Condition:
Relapsed or Refractory Multiple Myeloma (RRMM)
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Other
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Purinostat Mesylate 3mg/m2
Description:
3 mg/m2 Purinostat Mesylate + 4mg Pomalidomide + 20mg Dexamethasone.
Arm group label:
A group
Arm group label:
B group
Intervention type:
Drug
Intervention name:
Purinostat Mesylate 4 mg/m2
Description:
4 mg/m2 Purinostat Mesylate + 4mg Pomalidomide + 20mg Dexamethasone.
Arm group label:
A group
Arm group label:
B group
Intervention type:
Drug
Intervention name:
Purinostat Mesylate 6 mg/m2
Description:
6 mg/m2 Purinostat Mesylate + 4mg Pomalidomide + 20mg Dexamethasone.
Arm group label:
A group
Arm group label:
B group
Intervention type:
Drug
Intervention name:
Purinostat Mesylate 8.4 mg/m2
Description:
8.4 mg/m2 Purinostat Mesylate + 4mg Pomalidomide + 20mg Dexamethasone.
Arm group label:
A group
Arm group label:
B group
Summary:
Primary Purpose Phase Ib. Determine the maximum tolerated dose (MTD) of poystat mesylate
for injection in combination with fixed-dose pomalidomide capsules and dexamethasone in
patients with relapsed or refractory multiple myeloma (RRMM) at the recommended phase IIa
dose (RP2D).
Phase IIa. To further evaluate the preliminary efficacy of the RP2D dose of puesta
mesylate for injection in combination with fixed-dose pomalidomide capsules and
dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM).
Secondary Objectives Phase Ib
1. to evaluate the safety and tolerability of puesta mesylate for injection in
combination with fixed-dose pomalidomide capsules and dexamethasone in the treatment
of patients with relapsed or refractory multiple myeloma (RRMM);
2. to evaluate the pharmacokinetic and pharmacodynamic indices after combining
fixed-dose pomalidomide capsule and dexamethasone with puesta mesylate for injection
in patients with relapsed or refractory multiple myeloma (RRMM);
3. to observe the efficacy of injectable puesta mesylate combined with fixed-dose
pomalidomide capsules and dexamethasone in patients with relapsed or refractory
multiple myeloma (RRMM).
Phase IIa
1. To evaluate the safety and tolerability of puesta mesylate for injection in
combination with fixed-dose pomalidomide capsules and dexamethasone in patients with
relapsed or refractory multiple myeloma (RRMM).
2. To evaluate the population pharmacokinetic profile of puesta mesylate for injection
in combination with fixed-dose pomalidomide capsules and dexamethasone in patients
with relapsed or refractory multiple myeloma (RRMM).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. diagnosed with multiple myeloma (MM) by reference to the diagnostic criteria of the
Chinese Guidelines for the Diagnosis and Treatment of Multiple Myeloma (Revised
2022);
2. those who have received at least one line of prior systemic antimyeloma therapy
(which must include lenalidomide and proteasome inhibitors; see Appendix 4 for
counts of myeloma treatment lines) and meet the definition of relapse or refractory;
Definition of relapse: disease progression that occurs at least 60 days from the
last treatment after the efficacy of a prior treatment regimen was evaluated at MR
or better (except for those who relapsed more than 1 year after treatment);
Definition of refractory: progression during prior therapy or progression within 60
days of the last treatment; or failure to achieve MR or better after at least 2
prior courses of therapy; or treatment intolerance.
3. age 18-75 years, male or female, if of childbearing potential subjects should be on
effective contraception and must agree to comply with all contraceptive
requirements:
1) Females of childbearing potential must agree to and comply with the contraceptive
measures specified in the protocol: beginning 4 weeks prior to treatment with this
product, two reliable methods of contraception are required concurrently for the
duration of the treatment, during the dose suspension, and for 4 weeks after
termination of the treatment (one highly effective method of contraception-tubal
ligation, intrauterine device, hormonal (contraceptive pills, injections, patches,
vaginal rings, or implants), or partner's vasectomy, and another effective
contraceptive method - male rubber or synthetic condom, diaphragm or cervical cap).
Effective contraception is needed even with a history of infertility unless due to
hysterectomy; 2) Men of childbearing potential must use a rubber or synthetic condom
at all times during sexual contact with women of childbearing potential beginning 4
weeks prior to treatment with this product, during the treatment period, during the
dose suspension period, and for 4 weeks after termination of treatment, even if they
have had a successful vasectomy; 4. subjects with multiple myeloma who have
measurable M protein, i.e., at least one of the following 3 measurements:
1. Serum M protein ≥ 0.5 g/dL (5 g/L);
2. Urine M protein ≥ 200 mg/24h;
3. Serum free light chain assay: in the case of an abnormal serum free light chain
ratio (less than 0.26 or greater than 1.65), an affected free light chain level
≥10mg/dL (100mg/L); 5. hematologic fulfillment of the following conditions:
1) ANC ≥ 1.0 x 109/L (without granulocyte colony-stimulating factor within 7 days),
with no specific requirement for neutrophil count when ≥ 50% of the bone marrow is
plasma cells; 2) PLT ≥75 × 109/L (no platelet transfusion or use of thrombopoietin
within 7 days), and platelets ≥50 × 109/L were eligible for enrollment when ≥50% of
plasma cells were present in the bone marrow; 3) Hemoglobin ≥ 80 g/L (no red blood
cell suspension infusion or use of erythropoietin within 7 days); 6. Liver and
kidney function tests fulfill the following conditions:
1. TBIL ≤ 1.5 x ULN;
2. ALT and AST are ≤ 2.5 x ULN;
3. Glomerular filtration rate (GFR) ≥ 30mL/min/1.73m2 (Cockcroft-Gault formula) without
the effects of dialysis therapy; 7. ability to receive and have access to
antithrombotic medications such as low molecular heparin sodium, heparin, warfarin
or aspirin; 8. an ECOG (Appendix 2) score of 0-2 and an expected survival of ≥12
weeks; 9. subjects voluntarily enrolled in the study and signed an informed consent
form.
Exclusion Criteria:
1. those with prior antitumor therapy with histone deacetylase (HDAC) inhibitors
(except cedarbenazine), antibody-coupled degradation agents (DAC), HSP90 inhibitors,
or valproic acid; or those who, in the judgment of the investigator, are intolerant
to treatment with the same type of drug as HDAC inhibitors, pomalidomide,
thalidomide, lenalidomide, or the like (e.g., grade ≥3 rash during prior use, severe
refractory myelosuppression, etc.);
2. those with disease progression following prior treatment with standard dose
pomalidomide;
3. allergic reactions to the components of the test drug involved in this trial;
4. a diagnosis of non-secretory MM (defined as a subject who is completely
non-secretory or who has a small amount of free light chain but the affected light
chain is less than 100 mg/L), or MM in combination with amyloidosis, or plasma cell
leukemia, either primary or during the course of therapy
5. those with active new thrombosis or who are unable to receive antithrombotic
therapy;
6. other malignant tumors within 5 years prior to screening, with the exception of
cured carcinoma in situ (e.g., cervix, breast, bladder, etc.), basal cell carcinoma
of the skin, squamous epithelial cell carcinoma of the skin, or early-stage prostate
carcinoma (with clinical staging of Tla or T1b);
7. those who have a combination of central nervous system disorders and require
treatment for such disorders
8. peripheral neuropathy ≥ grade 3; and
9. co-morbidities requiring long-term treatment with immunosuppressive drugs or
steroids; 10. active infectious diseases;
10. those with comorbid active infectious diseases, including the following:
1) Hepatitis B Surface Antigen (HbsAg) or Hepatitis B Core Antibody (HbcAb) positive
with HBV-DNA quantification higher than the upper limit of normal value 2) Positive
Hepatitis C Virus Antibody (HCV-Ab) with HCV RNA quantification above the upper
limit of normal; 3) human immunodeficiency virus antibody (HIV-Ab) or anti-syphilis
spirochete antibody (TP-Ab) positive; 11. subjects with any of the following:
1. Cardiac insufficiency ≥ grade 3 by NYHA classification (Appendix 1) criteria;
2. Myocardial infarction within 6 months;
3. Poorly controlled angina, including variant angina, within 6 months;
4. clinically significant arrhythmia;
5. ECG QTcF >450 ms (men) and QTcF >470 ms (women) (Fridericia formula);
6. echocardiographic indication of left ventricular ejection fraction <50%; 12. a
combination of severe infectious disease requiring systemic intravenous antibiotic
therapy 2 weeks prior to the first dose; 13. those who have received an allogeneic
hematopoietic stem cell transplant within 12 months, or those who have active
graft-versus-host disease (GVHD) or GVHD requiring immunosuppressive therapy more
than 12 months after the allogeneic hematopoietic stem cell transplant; 14. who have
participated in another clinical trial within 4 weeks prior to the first dose; 15.
those who have received other antitumor therapy (including herbal antitumor therapy,
except for ≤20 mg/day of prednisone and its equivalent dose of steroid hormones)
within 2 weeks prior to the first administration of the drug; 16. those who have not
recovered to Grade 1 or below from toxic reactions to prior antitumor therapy
(except alopecia, malaise and those limited by entry criteria #6); 17. those who
have received major surgical treatment within 4 weeks prior to the first dose and
have not fully recovered; 18. women who are pregnant or breastfeeding; 19. persons
who, in the opinion of the investigator, have other factors that make them
unsuitable for participation in the trial (e.g., uncontrolled active hypertension,
uncontrolled active diabetes mellitus, poor adherence, substance abuse, etc.).
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
West China Hospital Sichuan University
Address:
City:
Chengdu
Zip:
610000
Country:
China
Contact:
Last name:
JingZe Zuo
Phone:
028-85422654
Email:
huaxilunli@163.com
Start date:
June 26, 2024
Completion date:
April 1, 2026
Lead sponsor:
Agency:
Chengdu Zenitar Biomedical Technology Co., Ltd
Agency class:
Industry
Source:
Chengdu Zenitar Biomedical Technology Co., Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06484829
