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Safety and Efficacy of MAK683 in Adult Patients With Advanced Malignancies

Primary Purpose

Diffuse Large B-cell Lymphoma

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
MAK683
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-cell Lymphoma focused on measuring MAK683, DLBCL, EED - Embryonic ectoderm development, EZH2 - Enhancer of zeste homolog 2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Eastern Cooperative Oncology Group (ECOG): 0 to 2
  2. Relapsed or refractory diffuse large B cell lymphoma with measurable disease as determined by Non-Hodgkin's Lymphoma Cheson response criteria (2014)
  3. Advanced or recurrent/metastatic solid tumor, including nasopharyngeal carcinoma, castration-resistant prostate cancer, gastric cancer, ovarian clear cell carcinoma and sarcoma, with measurable disease as determined by RECIST 1.1.

Exclusion Criteria:

  1. Other malignant diseases than the ones being treated in this study
  2. Severe and/or uncontrolled medical conditions that in the investigator's opinion could affect the safety of individual or impair the assessment of study result.
  3. B-cell lymphoma patients who have received prior allogeneic stem cell transplant
  4. Patient have received anti-cancer therapies within defined time frames prior to the first dose of study treatment
  5. Symptomatic central nervous system (CNS) involvement which are neurologically unstable or requiring increasing doses of steroids to control.
  6. Patient having out of range laboratory values defined as:

1) Insufficient bone marrow function at screening:

  • Platelets ≤ 50,000/mm3
  • Hemoglobin (Hgb) ≤ 80 g/L
  • Absolute neutrophil count (ANC) ≤ 1000/mm3 2) Insufficient hepatic and renal function at screening:
  • ALP, ALT, and AST > 3 x ULN (>5 x ULN if subject has liver metastases)
  • Total bilirubin >1.5 x ULN
  • Serum creatinine > 1.5 x ULN and/or creatinine clearance ≤ 50 mL/min

Sites / Locations

  • University of California San Francisco
  • UCLA Santa Monica Hematology / Oncology
  • Uni of TX MD Anderson Cancer Cntr Dept of Onc
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Phase I - All

Arm Description

advanced stage (relapsed/refractory or recurrent/metastatic) malignancy limited to the following malignancies; DLBCL, nasopharyngeal carcinoma, gastric cancer, ovarian cancer, prostate cancer and sarcoma.

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicities (DLTs)
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Safety and tolerability
Incidence and severity of AEs, SAEs, changes in laboratory values, vital signs and ECGs, dose interruptions and reductions

Secondary Outcome Measures

Overall Response Rate (ORR)
Duration of overall response (DOR)
Progression-free survival (PFS)
Best Overall Response (BOR)
Peak Plasma Concentration (Cmax) of MAK683
Pharmacokinetic profile of MAK683
Area Under the Plasma Concentration (AUC) Time Curve of MAK683
Pharmacokinetic profile of MAK683
Half-Life of MAK683
Pharmacokinetic profile of MAK683
H3K27 tri methylation level in PBMC
Cycle 1 Day 1,8,15 Cycle 2 Day1 Cycle 3 Day 1 End of treatment (EOT); Disease progression PBMC: peripheral blood mononuclear cell

Full Information

First Posted
September 2, 2016
Last Updated
July 10, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02900651
Brief Title
Safety and Efficacy of MAK683 in Adult Patients With Advanced Malignancies
Official Title
A Phase I/II, Multicenter, Open-label Study of MAK683 in Adult Patients With Advanced Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 3, 2016 (Actual)
Primary Completion Date
July 26, 2024 (Anticipated)
Study Completion Date
July 26, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this Phase I/II study is to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and to evaluate the safety, antitumor activity and pharmacokinetic (PK) profile of MAK683 in patients with advanced malignancies such as Diffuse Large B cell Lymphoma (DLBCL), nasopharyngeal carcinoma (NPC) or other advanced solid tumors for whom no further effective standard treatment is available.
Detailed Description
The purpose phase I of this trial is to characterize safety and tolerability and determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of MAK683. The purpose of the phase II of this trial is to evaluate the anti-tumor activity of MAK683. Phase II part will not be opened.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-cell Lymphoma
Keywords
MAK683, DLBCL, EED - Embryonic ectoderm development, EZH2 - Enhancer of zeste homolog 2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
139 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase I - All
Arm Type
Experimental
Arm Description
advanced stage (relapsed/refractory or recurrent/metastatic) malignancy limited to the following malignancies; DLBCL, nasopharyngeal carcinoma, gastric cancer, ovarian cancer, prostate cancer and sarcoma.
Intervention Type
Drug
Intervention Name(s)
MAK683
Intervention Description
Drug: MAK683
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicities (DLTs)
Description
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
up to 28 days
Title
Safety and tolerability
Description
Incidence and severity of AEs, SAEs, changes in laboratory values, vital signs and ECGs, dose interruptions and reductions
Time Frame
up to approximately 3 years
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Time Frame
up to 30 months
Title
Duration of overall response (DOR)
Time Frame
up to 30 months
Title
Progression-free survival (PFS)
Time Frame
up to 30 months
Title
Best Overall Response (BOR)
Time Frame
up to 30 months
Title
Peak Plasma Concentration (Cmax) of MAK683
Description
Pharmacokinetic profile of MAK683
Time Frame
30 months
Title
Area Under the Plasma Concentration (AUC) Time Curve of MAK683
Description
Pharmacokinetic profile of MAK683
Time Frame
30 months
Title
Half-Life of MAK683
Description
Pharmacokinetic profile of MAK683
Time Frame
30 months
Title
H3K27 tri methylation level in PBMC
Description
Cycle 1 Day 1,8,15 Cycle 2 Day1 Cycle 3 Day 1 End of treatment (EOT); Disease progression PBMC: peripheral blood mononuclear cell
Time Frame
up to day 15

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG): 0 to 2 Relapsed or refractory diffuse large B cell lymphoma with measurable disease as determined by Non-Hodgkin's Lymphoma Cheson response criteria (2014) Advanced or recurrent/metastatic solid tumor, including nasopharyngeal carcinoma, castration-resistant prostate cancer, gastric cancer, ovarian clear cell carcinoma and sarcoma, with measurable disease as determined by RECIST 1.1. Exclusion Criteria: Other malignant diseases than the ones being treated in this study Severe and/or uncontrolled medical conditions that in the investigator's opinion could affect the safety of individual or impair the assessment of study result. B-cell lymphoma patients who have received prior allogeneic stem cell transplant Patient have received anti-cancer therapies within defined time frames prior to the first dose of study treatment Symptomatic central nervous system (CNS) involvement which are neurologically unstable or requiring increasing doses of steroids to control. Patient having out of range laboratory values defined as: 1) Insufficient bone marrow function at screening: Platelets ≤ 50,000/mm3 Hemoglobin (Hgb) ≤ 80 g/L Absolute neutrophil count (ANC) ≤ 1000/mm3 2) Insufficient hepatic and renal function at screening: ALP, ALT, and AST > 3 x ULN (>5 x ULN if subject has liver metastases) Total bilirubin >1.5 x ULN Serum creatinine > 1.5 x ULN and/or creatinine clearance ≤ 50 mL/min
Facility Information:
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
UCLA Santa Monica Hematology / Oncology
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Uni of TX MD Anderson Cancer Cntr Dept of Onc
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Novartis Investigative Site
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Novartis Investigative Site
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
Novartis Investigative Site
City
Villejuif Cedex
State/Province
Île-de-France
ZIP/Postal Code
94800
Country
France
Facility Name
Novartis Investigative Site
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Novartis Investigative Site
City
Koeln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Novartis Investigative Site
City
Hong Kong
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Facility Name
Novartis Investigative Site
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
Facility Name
Novartis Investigative Site
City
Fukuoka-city
State/Province
Fukuoka
ZIP/Postal Code
811-1395
Country
Japan
Facility Name
Novartis Investigative Site
City
Sunto Gun
State/Province
Shizuoka
ZIP/Postal Code
411 8777
Country
Japan
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
168583
Country
Singapore
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Learn more about this trial

Safety and Efficacy of MAK683 in Adult Patients With Advanced Malignancies

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