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Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04502394
Recruitment Status : Not yet recruiting
First Posted : August 6, 2020
Last Update Posted : August 6, 2020
Sponsor:
Information provided by (Responsible Party):
Kartos Therapeutics, Inc.

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

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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
Estimated Study Start Date : October 2020
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2024


Arm Intervention/treatment
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

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 :
  1. 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.

  2. 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.

  3. 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 :
  1. 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).

  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 parameters from a single dose will be area under the curve (AUC).

  3. 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).

  4. 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.

  5. 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.

  6. 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.

  7. 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
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Contact: John Mei 650-542-0136 jmei@kartosthera.com
Contact: Michael Yee 650-839-7361 myee@kartosthera.com

Sponsors and Collaborators
Kartos Therapeutics, Inc.
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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 6, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, B-Cell