Ignite Creation Date:
2024-05-06 @ 8:21 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06351644
Status:
RECRUITING
Last Update Posted:
2024-04-08
First Post:
2024-04-02
Brief Title:
ON 123300 Narazaciclib and Dexamethasone in Patients With Relapsed andor Refractory Multiple Myeloma
Sponsor:
Adriana Rossi
Organization:
Icahn School of Medicine at Mount Sinai
Study Overview
Official Title:
A Phase III Study to Assess the Safety and Tolerability of the Combination of Oral ON 123300 Narazaciclib and Dexamethasone in Patients With Relapsed andor Refractory Multiple Myeloma
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Multiple myeloma MM is a malignancy characterized by uncontrolled proliferation of plasma cells for which there is an urgent and unmet need to develop new effective therapeutics Onconova Therapeutics has developed a first-in-class oral inhibitor of CDK4 and ARK5 ON 123300 NARAZACICLIB which shows potent anti-myeloma activity in vitro and in vivo in preclinical models and is undergoing evaluation in Phase 1-2 trials worldwide
In this study the researchers will test the safety and preliminary efficacy of inhibition of CDK4 and ARK5 by ON 123300 NARAZACICLIB in combination with dexamethasone in myeloma patients in a Phase III clinical trial
In this study the researchers will test the safety and preliminary efficacy of inhibition of CDK4 and ARK5 by ON 123300 NARAZACICLIB in combination with dexamethasone in myeloma patients in a Phase III clinical trial
Detailed Description:
ON 123300 NARAZACICLIB is a multi-targeted kinase inhibitor targeting cyclin-dependent kinases CDK 4 and 6 AMPK-related protein kinase 5 ARK5 colony-stimulating factor 1 receptor CSF1R tyrosine-protein kinase kit c-Kit and fms-like tyrosine kinase FLT3 at low nM concentrations that can arrest the cell cycle and thus block tumor cell proliferation and inhibit the growth of cancer cells As an apoptotic and antiproliferative agent ON 123300 NARAZACICLIB modulates the levels and activities of regulatory proteins of the cell cycle including cyclin D1 and inhibits retinoblastoma Rb protein binding ON 123300 NARAZACICLIB inhibits cancer cell growth and suppresses deoxyribonucleic acid DNA synthesis by preventing CDK-mediated G1-S phase transition followed by tumor cell death by induction of mitochondria-mediated apoptosis
ON 123300 NARAZACICLIB is being investigated for potential treatment of patients with solid tumors and hematologic malignancies as a single agent and in combination with other anticancer therapies This is supported by antiproliferative and cytotoxic effects that have been observed with ON 123300 NARAZACICLIB in a wide variety of malignant human cell lines in cell-based assay systems and in mouse xenograft models of breast cancer colon cancer mantle cell lymphoma multiple myeloma and melanoma Based on the nonclinical efficacy models Onconova intends to study patients with solid tumors and hematologic malignancies
As of the data cutoff date 05 January 2022 Onconova-sponsored Study 19-01 United States US is an ongoing exploratory Phase 1 dose escalation study to assess the safety tolerability and pharmacokinetics PK of ON 123300 NARAZACICLIB capsules administered orally as escalating daily doses in patients with advanced cancer relapsed or refractory to at least 1 prior line of therapy
Enrolled patients will continue 28-day cycles of ON 123300 NARAZACICLIB dexamethasone as long as the drug shows anti-myeloma activity with a disease response PR PR VGPR CR and the patient does not exhibit any DLTs and the study is open Patients will continue the regimen until disease progressionintolerable toxicitydeath withdrawal OR for a maximum up to 2 years after enrollment Treatment would be discontinued for Grade 4 or above toxicity For Grade 2-3 toxicity will challenge with the lower dose first before discontinuing Grading of toxicities per CTCAE version 50
ON 123300 NARAZACICLIB is being investigated for potential treatment of patients with solid tumors and hematologic malignancies as a single agent and in combination with other anticancer therapies This is supported by antiproliferative and cytotoxic effects that have been observed with ON 123300 NARAZACICLIB in a wide variety of malignant human cell lines in cell-based assay systems and in mouse xenograft models of breast cancer colon cancer mantle cell lymphoma multiple myeloma and melanoma Based on the nonclinical efficacy models Onconova intends to study patients with solid tumors and hematologic malignancies
As of the data cutoff date 05 January 2022 Onconova-sponsored Study 19-01 United States US is an ongoing exploratory Phase 1 dose escalation study to assess the safety tolerability and pharmacokinetics PK of ON 123300 NARAZACICLIB capsules administered orally as escalating daily doses in patients with advanced cancer relapsed or refractory to at least 1 prior line of therapy
Enrolled patients will continue 28-day cycles of ON 123300 NARAZACICLIB dexamethasone as long as the drug shows anti-myeloma activity with a disease response PR PR VGPR CR and the patient does not exhibit any DLTs and the study is open Patients will continue the regimen until disease progressionintolerable toxicitydeath withdrawal OR for a maximum up to 2 years after enrollment Treatment would be discontinued for Grade 4 or above toxicity For Grade 2-3 toxicity will challenge with the lower dose first before discontinuing Grading of toxicities per CTCAE version 50
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None