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Primary Purpose Phase Ib. To determine the Maximum Tolerated Dose (MTD) and establish the Recommended Phase IIa Dose (RP2D) of Purinostat Mesylate for Injection combined with fixed-dose Pomalidomide Capsules and Dexamethasone in patients with relapsed or refractory multiple myeloma.
Phase IIa. To further evaluate the safety and tolerability of Purinostat Mesylate for Injection at the RP2D combined with fixed-dose Pomalidomide Capsules and Dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM).
Secondary Objectives Phase Ib
Phase IIa
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A group | Experimental | A: Treatment Cycle Regimen - Regimen A (2-Week On/1-Week Off) - 21-Day Cycle Purinostat Mesylate for Injection: Intravenous infusion on Days 1, 4, 8, and 11 of each 21-day (3-week) cycle during the Continuation Dosing Phase Ib and Phase IIa; Pomalidomide Capsules: Oral administration once daily at 4 mg for 14 consecutive days followed by a 7-day rest period, with each cycle lasting 21 days (3 weeks); Dexamethasone Acetate Tablets: 20 mg orally administered on Days 1, 4, 8, and 11 of each treatment cycle. |
|
| B group | Experimental | B: Treatment Cycle Regimen - Regimen B (3-Week On/1-Week Off) - 28-Day Cycle Purinostat Mesylate for Injection: Intravenous infusion on Days 1, 4, 15, and 18 of each 28-day (4-week) cycle during the Continuation Dosing Phase 1b and Phase IIa; Pomalidomide Capsules: Oral administration once daily at 4 mg for 21 consecutive days followed by a 7-day rest period, with each cycle lasting 28 days (4 weeks); Dexamethasone Acetate Tablets: 20 mg orally administered on Days 1, 4, 15,and 18 of each treatment cycle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Purinostat Mesylate 4 mg/m2 | Drug | 4 mg/m2 Purinostat Mesylate + 4mg Pomalidomide + 20mg Dexamethasone. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose-limiting toxicity (DLT) | One or more unacceptable toxic reactions following administration of the drug, resulting in the inability to continue increasing the dose or prolonging the dosing cycle | Day 21/Day 28 |
| Maximum Tolerated Dose (MTD) | The maximum dose or concentration of a drug that does not cause death in experimental animals in experiments other than acute toxicity animal experiments (short-term repetitive experiments, subchronic toxicity experiments, chronic toxicity experiments). | Day 21/Day 28 |
| Objective remission rate (ORR) | Defined as the proportion of subjects achieving a strict complete remission (sCR) + complete remission (CR) + very good partial remission (VGPR) + partial remission (PR); | Day 21/Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Complete Remission Rate (CRR) | Proportion of subjects with sCR+CR | Day 21/Day 28 |
| Duration of efficacy (DOR) | Duration of first remission (PR and above) to disease progression or death; |
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Inclusion Criteria:
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) 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:
Exclusion Criteria:
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Liangkun Sun, bachelor | Contact | 15885742617 | liangkunsun@zenitar.cn | |
| Zheng Jiang, bachelor | Contact | 19048075294 | zhengjiang@zenitar.cn |
| Name | Affiliation | Role |
|---|---|---|
| Ting Niu, Doctor | West China Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| West China Hospital Sichuan University | Recruiting | Chengdu | Sichuan | 610000 | China |
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| Purinostat Mesylate 6 mg/m2 | Drug | 6 mg/m2 Purinostat Mesylate + 4mg Pomalidomide + 20mg Dexamethasone. |
|
| Purinostat Mesylate 8.4 mg/m2 | Drug | 8.4 mg/m2 Purinostat Mesylate + 4mg Pomalidomide + 20mg Dexamethasone. |
|
| Day 21/Day 28 |
| Time to Relief (TTR) | Time from first dose to PR and beyond | Day 21/Day 28 |
| Progression-free survival (PFS) | Time from first dose to disease progression or death | Day 21/Day 28 |
| Overall survival (OS) | Time from first dose to death from all causes | Day 21/Day 28 |
| ID | Term |
|---|---|
| D012008 | Recurrence |
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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