Ibrutinib and Palbociclib in Treating Patients With Previously Treated Mantle Cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT02159755|
Recruitment Status : Active, not recruiting
First Posted : June 10, 2014
Last Update Posted : November 14, 2018
|Condition or disease||Intervention/treatment||Phase|
|CCND1 Positive Recurrent Mantle Cell Lymphoma t(11;14)||Drug: Ibrutinib Other: Laboratory Biomarker Analysis Drug: Palbociclib Other: Pharmacological Study||Phase 1|
I. To evaluate the safety of ibrutinib plus PD 0332991 (palbociclib) in patients with previously treated mantle cell lymphoma (MCL) and select the recommended phase 2 dose schedule.
I. To estimate the toxicity profile of ibrutinib plus PD 0332991 (palbociclib). II. To estimate the overall response rate (ORR) and complete response (CR) rates.
III. To estimate the progression-free survival (PFS). IV. To estimate the response duration (RD).
I. To evaluate the genomic profile of MCL cells pre-treatment and at relapse. II. To estimate the pharmacokinetic profile of ibrutinib when given concurrently with PD 0332991 (palbociclib).
III. To evaluate the level of cell-free tumor deoxyribonucleic acid (DNA) over time in conjunction with response to therapy.
IV. To evaluate the presence of circulating MCL cells over time.
OUTLINE: This is a dose-escalation study.
Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28 and palbociclib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Ibrutinib Plus PD 0332991 (Palbociclib) in Patients With Previously Treated Mantle Cell Lymphoma|
|Actual Study Start Date :||May 20, 2014|
|Actual Primary Completion Date :||May 11, 2017|
Experimental: Treatment (ibrutinib, palbociclib)
Patients receive ibrutinib PO QD on days 1-28 and palbociclib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Recommended phase II dose of the combination of ibrutinib and palbociclib defined as the highest dose level at which no more than 1/6 patients present with a dose limiting toxicity (DLT) [ Time Frame: Up to 28 days ]DLT will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Overall response rate (ORR) [ Time Frame: Up to 2 years ]Will be evaluated according to the revised response criteria of the International Working Group.
- Complete response (CR) rate [ Time Frame: Up to 2 years ]Will be evaluated according to the revised response criteria of the International Working Group.
- Partial response rate [ Time Frame: Up to 2 years ]Will be evaluated according to the revised response criteria of the International Working Group.
- Progression-free survival (PFS) [ Time Frame: Time from entry onto study until first documentation of objective tumor progression or death due to any cause, whichever occurs first, assessed up to 2 years ]Estimated and plotted by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula. Log-rank test will be applied to compare the difference between survival curves with two-sided significance level of 0.05.
- Response duration (RD) [ Time Frame: Time from when criteria for response (CR or partial response [PR]) are met, until first documentation of relapse or progression, assessed up to 2 years ]Estimated and plotted by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula. Log-rank test will be applied to compare the difference between survival curves with two-sided significance level of 0.05.
- Incidence of toxicities, assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 [ Time Frame: Up to 2 years ]A listing of all adverse events (AEs) including detailed information for each AE will be presented. The number and percentage of patients who experienced any: AE, serious adverse events (SAE), treatment-related AE, and treatment-related SAE will be summarized. AE data will be presented by dose for all cycles, cycle 1 only and cycles > 1, as appropriate. Additional summaries of AE data and of other safety data will be presented in tabular and/or graphical format and summarized descriptively, as appropriate.
- Genetic alterations [ Time Frame: Up to 2 years ]Sequencing data will be evaluated for mutations and copy number variations (CNV) and the status of wild type and alterations will be assigned. Fisher's exact test will be used to assess the association between genetic alterations and response to study drugs. A moderated t-test will be applied to the transformed ribonucleic acid sequencing data to assess the expression difference between wild-type and altered genes. The Benjamini-Hochberg procedure will be used to adjust the p value and use the false discovery rate 10% as the cutoff to declare significance.
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): NCT02159755
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|Weill Medical College of Cornell University|
|New York, New York, United States, 10065|
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Peter Martin||Weill Medical College of Cornell University|