Pevonedistat and Ibrutinib in Treating Participants With Relapsed or Refractory CLL or Non-Hodgkin Lymphoma
|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. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03479268|
Recruitment Status : Active, not recruiting
First Posted : March 27, 2018
Last Update Posted : May 13, 2022
|Condition or disease||Intervention/treatment||Phase|
|B-Cell Prolymphocytic Leukemia Recurrent Chronic Lymphocytic Leukemia Recurrent Diffuse Large B-Cell Lymphoma Recurrent Follicular Lymphoma Recurrent Lymphoplasmacytic Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Non-Hodgkin Lymphoma Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Diffuse Large B-Cell Lymphoma Refractory Follicular Lymphoma Refractory Lymphoplasmacytic Lymphoma Refractory Mantle Cell Lymphoma Refractory Marginal Zone Lymphoma Refractory Non-Hodgkin Lymphoma Refractory Small Lymphocytic Lymphoma Richter Syndrome||Drug: Ibrutinib Other: Laboratory Biomarker Analysis Drug: Pevonedistat Other: Pharmacokinetic Study Other: Pharmacological Study||Phase 1|
I. To evaluate the safety and tolerability of pevonedistat administered in combination with ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL).
I. Overall response rate (ORR) will be determined based on the proportion of study participants who achieve complete response (CR), complete response with incomplete marrow recovery (CRi), partial response (PR) or nodular partial response (nPR) assessed after completion of therapy.
II. Event-free survival (EFS), defined as the interval between the date of first study treatment and the date of objective signs of disease recurrence, subsequent anti-leukemic therapy, or death, whichever is first reported.
OUTLINE: This is a dose-escalation study of pevonedistat.
Participants receive pevonedistat intravenously (IV) over 1 hour on days 1, 3, and 5, and ibrutinib orally (PO) daily on days 2-21 of course 1 and days 1-21 of subsequent courses. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Participants then receive only ibrutinib PO daily on days 1-21. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants will be followed up for every 3 months
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Pevonedistat (MLN4924, TAK924) in Combination With Ibrutinib in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma|
|Actual Study Start Date :||March 22, 2018|
|Estimated Primary Completion Date :||April 1, 2023|
|Estimated Study Completion Date :||April 2, 2023|
Experimental: Treatment (pevonedistat, ibrutinib)
Participants receive pevonedistat IV over 1 hour on days 1, 3, and 5, and ibrutinib PO daily on days 2-21 of course 1 and days 1-21 of subsequent courses. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Participants then receive only ibrutinib PO daily on days 1-21. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacokinetic Study
Other: Pharmacological Study
- Incidence of dose limiting toxicities (DLTs) [ Time Frame: Up to 42 days ]
- Incidence of adverse events (AEs), serious AEs (SAEs), dose interruptions, reductions and dose intensity Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 30 days after last course of treatment ]All adverse events will be tabulated and summarized by major organ category, grade, anticipation, and drug attribution. SAE specific incidence and exact 95% confidence interval will be provided where appropriate.
- Overall response rate (ORR) determined based on proportion of participants who achieve complete response (CR), with incomplete marrow recovery (CRi), partial response (PR), or nodular partial response (nPR) [ Time Frame: Up to 1 year ]According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria in patients with chronic lymphocytic leukemia (CLL) and Lugano criteria in patients with non-Hodgkin lymphoma (NHL). The ORR, along with exact two-sided 95% confidence intervals, will be reported for the study.
- Event-free survival (EFS) [ Time Frame: From date of first study treatment until progression, start of anti-leukemic therapy, or death, assessed up to 4 years ]Defined as the interval between the date of first study treatment and the date of objective signs of disease recurrence, subsequent anti-leukemic therapy, or death, whichever is first reported. The Kaplan-Meier product limit method will be used to estimate progression-free survival (PFS) of the median PFS and PFS rates at clinically relevant time points will be provided with the 95% confidence interval (CI).
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): NCT03479268
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010|
|United States, New York|
|Roswell Park Comprehensive Cancer Center|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||Alexey Danilov||City of Hope Medical Center|