Trial record 1 of 1 for:
NCT 04502394
Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL
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| ClinicalTrials.gov Identifier: NCT04502394 |
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Recruitment Status :
Recruiting
First Posted : August 6, 2020
Last Update Posted : August 4, 2022
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Sponsor:
Kartos Therapeutics, Inc.
Information provided by (Responsible Party):
Kartos Therapeutics, Inc.
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Brief Summary:
This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, combined with acalabrutinib for the treatment of adults with Diffuse Large B-Cell Lymphoma and Chronic Lymphocytic Leukemia. Participants must be relapsed/refractory (having failed prior therapy)
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Diffuse Large B Cell Lymphoma Chronic Lymphocytic Leukemia Non Hodgkin Lymphoma | Drug: KRT-232 Drug: acalabrutinib | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 84 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | An Open-label, Phase 1b/2 Study of KRT-232 in combination with acalabrutinib in Subjects with B-cell Non-Hodgkin Lymphoma |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma or Relapsed/Refractory Chronic Lymphocytic Leukemia |
| Actual Study Start Date : | February 23, 2021 |
| Estimated Primary Completion Date : | October 2022 |
| Estimated Study Completion Date : | March 2024 |
Resource links provided by the National Library of Medicine
Drug Information
available for:
Acalabrutinib
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort 1 (R/R DLBCL)
KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle. Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle. |
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth Drug: acalabrutinib acalabrutinib is a BTK inhibitor anticancer drug taken by mouth
Other Name: ACP-196 |
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Experimental: Cohort 2 (R/R CLL)
KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle. Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle. |
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth Drug: acalabrutinib acalabrutinib is a BTK inhibitor anticancer drug taken by mouth
Other Name: ACP-196 |
Primary Outcome Measures :
- Primary Objective Phase 1b:To determine the KRT-232 maximum tolerated dose/ maximum administered dose (MTD/MAD) and recommended Phase 2 Dose (RP2D) in combination with acalabrutinib in subjects with R/R DLBCL or R/R CLL [ Time Frame: 56 Days ]Endpoint/Outcome Measures: Dose-limiting toxicities will be used to establish the MTD/MAD of KRT-232 in combination with acalabrutinib. The Safety Review Committee will determine the RP2D based on safety data of the combination of KRT-232 and acalabrutinib.
- Primary Objective Phase 2: Cohort 1: To determine the complete response (CR) [ Time Frame: 1 Year ]Endpoint/Outcome Measures: Cohort 1: The proportion of subjects with CR as assessed by investigators per the Lugano Classification.
- Primary Objective Phase 2: Cohort 2: To determine the rate of CR/complete remission with incomplete hematologic recovery (CRi) rate in R/R CLL [ Time Frame: 1 Year ]Endpoint/Outcome Measures: Cohort 2: The proportion of subjects with CR/CRi as assessed by investigators per iwCLL Response Criteria.
Secondary Outcome Measures :
- Phase 1b Secondary Objective: Pharmacokinetic (PK) profile [ Time Frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2 ]Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameter from a single dose will be estimated maximum concentration (Cmax).
- Phase 1b Secondary Objective: Pharmacokinetic (PK) profile [ Time Frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2 ]Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be area under the curve (AUC).
- Phase 1b Secondary Objective: Pharmacokinetic (PK) profile [ Time Frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2 ]Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be half-life (T1/2).
- Phase 1b Secondary Objective: Pharmacokinetic (PK) profile [ Time Frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2 ]Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameter from a single dose will be apparent clearance.
- Phase 1b Secondary Objective: Pharmacokinetic (PK) profile [ Time Frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2 ]Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be apparent volume of distribution using non-compartmental or compartmental PK methods with the software WinNonlin.
- Phase 2 Secondary Objective: Cohort 1 (R/R DLBCL): To determine the overall response rate (ORR) for R/R DLBCL subjects. [ Time Frame: 2 Years ]Endpoint/Outcome Measures: The proportion of subjects who achieve a partial response (PR) or better at any time point while on study.
- Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects [ Time Frame: 2 Years ]Endpoint/Outcome Measures: The proportion of subjects who achieve a PR or better at any time point while on study, as assessed by iwCLL Response Criteria
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Cohort 1: Confirmed diagnosis of TP53wt DLBCL (WHO); R/R DLBCL after at least 2 prior lines of treatment or 1 prior for patients who are ineligible for stem cell transplant
- Cohort 2: Confirmed diagnosis of TP53wt CLL (iwCLL); R/R CLL after at least 1 prior line of treatment
- ECOG 0 to 2
- Adequate hematologic, hepatic, and renal functions.
Exclusion Criteria:
- Prior treatment with any MDM2 inhibitor
- Prior treatment with any BTK inhibitor
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04502394
Contacts
| Contact: John Mei | 650-542-0136 | jmei@kartosthera.com | |
| Contact: Michael Yee | 650-839-7361 | myee@kartosthera.com |
Locations
Show 45 study locations
Sponsors and Collaborators
Kartos Therapeutics, Inc.
| Responsible Party: | Kartos Therapeutics, Inc. |
| ClinicalTrials.gov Identifier: | NCT04502394 |
| Other Study ID Numbers: |
KRT-232-111 |
| First Posted: | August 6, 2020 Key Record Dates |
| Last Update Posted: | August 4, 2022 |
| Last Verified: | August 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Kartos Therapeutics, Inc.:
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navtemadlin |
Additional relevant MeSH terms:
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Lymphoma Leukemia Lymphoma, B-Cell Leukemia, Lymphoid Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, Large B-Cell, Diffuse Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Hematologic Diseases Lymphoma, Non-Hodgkin Leukemia, B-Cell Chronic Disease Disease Attributes Pathologic Processes Acalabrutinib Tyrosine Kinase Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |