NCT06484829Phase 1, Phase 2Recruiting
Chengdu Zenitar Biomedical Technology Co., Ltd · West China Hospital Sichuan University, Chengdu, Sichuan
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
1. To evaluate the safety and tolerability of Purinostat Mesylate for Injection combined with fixed-dose Pomalidomide Capsules and Dexamethasone in the treatment of relapsed or refractory multiple myeloma.
2. To assess the pharmacokinetic (PK) parameters of the combination therapy in patients with relapsed or refractory multiple myeloma.
3. To observe the preliminary efficacy of the combination therapy in patients with relapsed or refractory multiple myeloma.
Phase IIa
1. To evaluate the preliminary efficacy of the combination therapy in patients with relapsed and refractory multiple myeloma (RRMM).
2. To characterize the population pharmacokinetic (PPK) profile of the combination therapy in patients with relapsed or refractory multiple myeloma (RRMM).
Eligibility: 18 Years to 75 Years · All · 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.
NCT04643002Phase 1, Phase 2Recruiting
Sanofi · Winship Cancer Institute of Emory University- Site Number : 8400010, Atlanta, Georgia
The purpose of this umbrella study is to evaluate isatuximab when combined with novel agents with or without dexamethasone in participants with relapsed or refractory myeloma. Substudy 01 is the control Substudy. Substudies 02, 03, and 06 are controlled experimental substudies. Substudies 04 and 05 are independent experimental substudies.
Eligibility: 18 Years to · All · * Participant must be 18 years of age inclusive or older.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
* Participants with relapsed or refractory MM who have received at least 2 prior lines of therapy for MM, including PIs and IMiDs (eg, Induction regimen with autologous stem cell transplant followed by maintenance is considered one line).
* RRMM with measurable disease:
* Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or
* Urine M protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or
* Serum free light chain (sFLC) MM without measurable M protein in serum or urine per previous criteria (serum Ig free light chain ≥10 mg/dL and abnormal serum Ig kappa lambda free light chain ratio \<0.26 or \>1.65).
* Men or woman or childbearing potential should agree to use contraception.
* Substudy 01, 06: Anti-CD38 therapy naïve or prior exposure to such drugs with a wash out of at least 12 months after the last dose. "Exposure" is defined as at least 2 cycles of therapy.
* Substudies 02, 03: Anti-CD38 therapy naïve or prior exposure to such drugs without being refractory but with a wash out of at least 6 months after the last dose. "Refractory" is defined as progressing within 60 days of last dose of anti-CD38 targeting therapy.
* Substudy 04: Anti-CD38 and anti-B cell maturation antigen (BCMA) therapy (if available) prior exposed participants with RRMM. For anti-CD38, "Exposure" is defined as at least 2 cycles of therapy. For anti-BCMA therapy if available, exposure is defined by at least 2 cycles of therapy.
* Substudy 05: Participants with RRMM with at least 2 cycles of prior exposure to anti-CD38 therapy. For participants to whom BCMA targeted therapy is available (ie, approved in their region and can be reimbursed), at least 2 cycles of prior exposure to a BCMA targeted agent is mandatory.
NCT05714839Phase 1, Phase 2Recruiting
GlaxoSmithKline · GSK Investigational Site, Bullhead City, Arizona
The study consists of three parts:
* Part 1: The primary purpose of this part aims to evaluate the safety, tolerability, and clinical activity of escalating doses of single agent belantamab in participants with refractory multiple myeloma (RRMM) who have received at least 3 prior therapies (4L+).
* Part 2: The primary purpose of this part is to evaluate the safety, tolerability, and clinical activity of different doses of belantamab in combination with a fixed dose of Belantamab mafodotin (delivered as separate drugs) in participants with RRMM who have received at least 3 prior therapies (4L+).
* Part 3: The Primary purpose of this part will evaluate the clinical activity of a selected dose of the belantamab in combination with the pomalidomide-dexamethasone (Pd) standard of care (SoC) backbone. The study will focus on participants with multiple myeloma who have undergone at least one prior line of therapy, including treatment with lenalidomide.
Eligibility: 18 Years to · All · Inclusion criteria
* Participants at the time of signing the Informed Consent Form (ICF) are at least 18 years old or are of the legal age of consent in the jurisdiction in which the study is taking place.
* Participants who have histologically or cytologically confirmed diagnosis of Multiple Myeloma (MM), as defined by the international myeloma working group (IMWG) and have progressed on or following the last line of treatment
* Part 1 and Part 2: Participants who have received at least 3 prior lines of anti-myeloma treatments, including any immunomodulatory drug (IMiDs lenalidomide, pomalidomide or thalidomide), a proteasome inhibitor, and an anti-CD38 monoclonal antibodies (mAb) (either in combination or separately).
* Part 3: Have received at least 1 prior line of treatment anti-myeloma treatments, including lenalidomide. Prior anti-CD38-containing regimen is not mandated, however no more than 70% of participants recruited may be anti-CD38 naïve.
* Participants with a history of Autologous stem cell transplant (ASCT) are eligible for study participation provided the following eligibility criteria are met:
* transplant was greater than (\>)100 days prior to screening.
* No active bacterial, viral, or fungal infection(s) present
* Eastern cooperative oncology group-performance status (ECOG-PS) of 0 to 2.
* Measurable disease defined as at least ONE of the following:
* Serum M-protein concentration greater than or equal to (\>=) 0.5 gram (g)/ deciliter (dL) (\>=5 gram/liter \[g/L\])
* Urine M-protein excretion \>=200 milligram (mg)/24 hours (\>=0.2 g/24 hours)
* Serum free light chain (FLC) assay: involved FLC level \>=10 mg/dL (\>=100 milligrams per liter \[mg/L\]) and an abnormal serum FLC ratio (less than \[\<\]0.26 or \>1.65)
* Have adequate organ system function as defined by the laboratory assessments
* All prior treatment-related toxicities (defined by National Cancer Institute-Common Toxicity Criteria for Adverse Events \[NCI-CTCAE\], v5.0, 2017) must be Grade less than or equal to (\<=)1 at the time of screening except for alopecia (any grade), neuropathy (Grade \<=2), or endocrinopathy managed with replacement therapy (any grade).
* Participants or legally authorized representative (LAR) (if applicable per local regulation) capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
* Male Participants (for parts 1b, 2 and 3):
* Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male Participants enrolled in part 1 (and expansion) cohort receiving belantamab monotherapy are not required to use contraception
* Male participants are eligible to participate in parts 2 and 3 if they agree to the following during the intervention period and for at least 6 months after the last dose of study intervention to allow for clearance of any altered sperm:
* Refrain from donating fresh unwashed semen PLUS either:
* Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
* Must agree to use contraception/barrier as detailed below
* Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of \<1 percent (%) per year when having sexual intercourse with POCBP who is not currently pregnant. Male participants should also use a condom when having sexual intercourse with pregnant females.
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
* Is NOT a Participant of child-bearing potential (POCBP) or
* Is a POCBP and using a contraceptive method that is highly effective (with a failure rate of \<1%
NCT04661137Phase 2Recruiting
Hackensack Meridian Health · Lombardi Comprehensive Cancer Center, Washington D.C., District of Columbia
This is a prospective, 2-arm (with an additional exploratory arm), open-label, multicenter study looking at the response rate of patients receiving selinexor (KPT-330), in combination with carfilzomib, daratumumab or pomalidomide.
Multiple Myeloma patients with documented disease progression or refractory disease while on current treatment with any carfilzomib-containing regimen (arm 1), any pomalidomide-containing regimen (arm 2) or any daratumumab-containing regimen (exploratory arm) will be included in the study. Patients will be assigned to the respective groups according to their current treatment. If a subject has received more than one of the above therapies, then assignment will be made at their physician's discretion (e.g treatment decision can be made based upon patient and physician preferred tolerance.).
Patients will receive treatment until progressive disease (PD), death, toxicity that cannot be managed by standard of care, or withdrawal, whichever occurs first.
Eligibility: 18 Years to · All · 1. Age ≥18 years at time of informed consent.
2. Histologically confirmed MM and evidence of disease progression while on one of the below MM regimens:
* Arm 1: Refractory to or disease progression while on a carfilzomib-containing regimen
* Arm 2: Refractory to or disease progression while on a pomalidomide-containing regimen
* Exploratory Arm: Refractory to or disease progression while on a daratumumab-containing regimen
3. Measurable disease as defined: Serum M-protein ≥ 0.5 g/dL; urine M-protein excretion at least 200 mg/24h; serum FLC ≥ 100 mg/L, provided that FLC is abnormal; if serum protein electrophoresis is felt to be unreliable for routine M-protein measurement (i.e. IgA MM) then quantitative Ig levels by nephelometry or turbidometry are acceptable; for non-secretory disease, bone marrow plasma cells ≥ 20% or a biopsy-proven target lesion by PET/CT or MRI is acceptable
4. Documented evidence of disease progression (by IMWG criteria) or refractory disease on the current treatment as defined as:
* Achieving SD or less for ≥ 1 cycle during treatment with regimens stated in #2 (i.e. relapsed) OR
* \<25% response (i.e. never achieved MR) or PD during or within 60 days from the end-of most recent MM regimen as listed in #2 (i.e. refractory).
5. Any non-hematological toxicities (except for peripheral neuropathy) that patients experienced from treatments in previous regimens have resolved to Grade 2 or less by Cycle 1 Day 1.
6. ECOG 2 or less
7. Adequate hepatic function within 28 days prior to C1D1:
1. Total bilirubin \< 1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of \< 3 × ULN), and
2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to \<2 × ULN.
8. Adequate renal function within 28 days prior to C1D1 as determined by estimated creatinine clearance of ≥ 30 mL/min, calculated using the Cockcroft and Gault formula (140 - Age) • Mass (kg)/ (72 • creatinine mg/dL); multiply by 0.85 if female (Cockcroft 1976).
9. Adequate hematopoietic function within 7 days prior to C1D1: total white blood cell (WBC) count ≥1500/mm3, absolute neutrophil count ≥1000/mm3, hemoglobin ≥8.5 g/dL and platelet count ≥75,000/mm3 (patients for whom \<50% of bone marrow nucleated cells are plasma cells) or ≥50,000/mm3 (patients for whom ≥50% of bone marrow nucleated cells are plasma cells).
1. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (eg, eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive growth factor support during the study.
2. Patients must have:
* At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the Screening hemoglobin assessment, and
* At least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment.
However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study.
10. Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment.
