- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03873493
A Study Evaluating the Efficacy of Venetoclax Plus Ibrutinib in Participants With T-cell Prolymphocytic Leukemia
A Prospective, Open-Label, Single-Arm, Phase 2, Multicenter Study Evaluating the Efficacy of Venetoclax Plus Ibrutinib in Subjects With T-Cell Prolymphocytic Leukemia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study is planned as an adaptive 2-stage design as follows:
Stage 1: Enroll 14 participants with relapsed or refractory (R/R) T-PLL and move to Stage 2 if 4 or more participants meet protocol-specified response criteria. Response assessment will be performed on a continued basis until all 14 participants have enrolled into Stage 1 and have completed the Week 24 disease assessment.
Stage 2: Enroll up to an additional 23 participants.
The study was stopped after Stage 1. Stage 2 was not conducted.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Victoria
-
Melbourne, Victoria, Australia, 3000
- Peter MacCallum Cancer Ctr /ID# 209554
-
-
-
-
Wien
-
Vienna, Wien, Austria, 1090
- Medizinische Universitaet Wien /ID# 208497
-
-
-
-
Uusimaa
-
Helsinki, Uusimaa, Finland, 00290
- Helsinki University Hospital /ID# 208108
-
-
-
-
-
Paris, France, 75013
- Hopital Pitie Salpetriere /ID# 208730
-
-
Auvergne-Rhone-Alpes
-
Pierre Benite CEDEX, Auvergne-Rhone-Alpes, France, 69495
- HCL - Hôpital Lyon Sud /ID# 208731
-
-
Hauts-de-France
-
Lille, Hauts-de-France, France, 59037
- CHRU Lille - Hopital Claude Huriez /ID# 208726
-
-
-
-
-
Cologne, Germany, 50937
- University Hospital Cologne /ID# 208834
-
-
-
-
-
Trieste, Italy, 34128
- Azienda Sanitaria Universitaria Giuliano Isontina /ID# 211487
-
-
-
-
-
Eindhoven, Netherlands, 5631 BM
- Maxima Medisch Centrum /ID# 207989
-
Groningen, Netherlands, 9713 GZ
- Universitair Medisch Centrum Groningen /ID# 207990
-
-
-
-
-
London, United Kingdom, SW3 6JJ
- The Royal Marsden NHS Foundation Trust /ID# 211263
-
-
Oxfordshire
-
Oxford, Oxfordshire, United Kingdom, OX3 9DU
- Oxford University Hospitals NHS Foundation Trust /ID# 211264
-
-
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute /ID# 207728
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905-0001
- Mayo Clinic - Rochester /ID# 207692
-
-
Texas
-
Houston, Texas, United States, 77030
- University of Texas MD Anderson Cancer Center /ID# 207746
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Adequate liver, kidney and hematology function per laboratory values as described in the protocol.
- Diagnosis of T-cell prolymphocytic leukemia (T-PLL) that requires treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
- Received prior alemtuzumab (unless unsuitable or unavailable).
Has no malignancies other than T-PLL that:
- currently require systemic therapies;
- were not previously treated with curative intention (unless the malignant disease is in a stable remission due to the discretion of the treating physician); or
- developed signs of progression after curative treatment.
Exclusion Criteria:
- History of or current decompensated cirrhosis including Child-Pugh class B or C, ascites, hepatic encephalopathy, or variceal bleeding.
- Has human T-cell lymphotropic virus, type 1.
- Prior allogeneic stem cell transplant within 6 months of study drug administration and requirement for graft versus host therapy.
- Has an uncontrolled or active infection including severe acute respiratory syndrome- coronavirus-2 (SARS-COV-2).
- Previously treated with a B-cell lymphoma (BCL)-2 inhibitor.
- Received a prohibited therapy within the specified time frame as described in the protocol.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Venetoclax + Ibrutinib
Participants received 400 mg venetoclax orally once a day after a 5-day ramp-up and 420 mg ibrutinib orally once a day for up to 2 years or until progressive disease, intolerability, or they became eligible for stem cell transplantation after achieving complete remission.
|
Venetoclax tablets taken orally once a day (QD).
Initially, venetoclax was administered utilizing a 5-step dose ramp-up over 5 days.
Subjects were hospitalized and closely monitored for 7 days.
The venetoclax ramp-up was administered in a daily manner: 20 mg on Week 1 Day 1, 50 mg on Week 1 Day 2, 100 mg on Week 1 Day 3, 200 mg on Week 1 Day 4, and 400 mg on Week 1 Day 5 and thereafter, once daily, until the end-of-treatment.
The dose of venetoclax may have been increased to 600 mg QD at Week 8 or thereafter.
Other Names:
Ibrutinib capsules taken orally once a day, 420 mg/day until the end-of-treatment.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (ORR)
Time Frame: Clinical response was assessed at Weeks 4, 8, 12, 16, and 24 for ORR assessment
|
ORR is defined as the percentage of participants achieving complete remission (CR), CR with incomplete bone marrow recovery (CRi), or partial remission (PR) as their best response per investigator assessment based on the T-PLL consensus criteria 2019. CR: All of the following response criteria must be met: Group A:
Group B:
CRi: All of the CR response criteria in Group A met; at least 1 parameter in Group B not achieved, unrelated to T-PLL, but related to drug toxicity. PR: At least 2 of the parameters in Group A and 1 parameter in Group B need to improve if previously abnormal. If only 1 parameter of both Groups A and B is abnormal prior to therapy, only 1 parameter needs to improve. |
Clinical response was assessed at Weeks 4, 8, 12, 16, and 24 for ORR assessment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-Free Survival (PFS)
Time Frame: From first dose of study drug to end of study; median time on study was 30.1 weeks.
|
Progression-free survival is defined as the time from the date of first dose of any study drug to the date of earliest disease progression or death. PFS was calculated using Kaplan-Meier methods. Response was assessed by the investigator based on the T-PLL consensus criteria 2019. Progressive disease (PD) is defined as meeting at least one of the criteria of Group A or Group B below: Group A:
Group B:
|
From first dose of study drug to end of study; median time on study was 30.1 weeks.
|
Duration of Response (DOR)
Time Frame: From first dose of study drug to end of study; median time on study was 30.1 weeks.
|
Duration of response is defined for participants who achieved a best overall response of CR, CRi, or PR as the time from the date of first response (CR, CRi, or PR) to the earliest date of disease progression or death. DOR was calculated using Kaplan-Meier methods. Response was assessed by the investigator based on the T-PLL consensus criteria 2019. Progressive disease is defined as meeting at least one of the criteria of Group A or Group B below: Group A:
Group B:
|
From first dose of study drug to end of study; median time on study was 30.1 weeks.
|
Time to Progression (TTP)
Time Frame: From first dose of study drug to end of study; median time on study was 30.1 weeks.
|
Time to progression is defined as the time from the date of the participant's first dose of any study drug to the date of earliest disease progression. TTP was calculated using Kaplan-Meier methods. Clinical response (laboratory and physical examination assessments) was assessed by the investigator according to the T-PLL consensus criteria 2019. Progressive disease is defined as meeting at least one of the criteria of Group A or Group B below: Group A:
Group B:
|
From first dose of study drug to end of study; median time on study was 30.1 weeks.
|
Event-free Survival (EFS)
Time Frame: From first dose of study drug to end of study; median time on study was 30.1 weeks.
|
Event-free survival is defined as time from participant's first dose of any study drug to the date of earliest disease progression, death, or start of a new anti-T-PLL therapy. EFS was calculated using Kaplan-Meier methods. Clinical response (laboratory and physical examination assessments) was assessed by the investigator according to the T-PLL consensus criteria 2019. Progressive disease is defined as meeting at least one of the criteria of Group A or Group B below: Group A:
Group B:
|
From first dose of study drug to end of study; median time on study was 30.1 weeks.
|
Disease Control Rate (DCR)
Time Frame: Clinical response was assessed at Weeks 4, 8, 12, 16, and 24 for DCR assessment
|
DCR is defined as the percentage of participants who achieved CR, CRi, PR, or stable disease (SD) as best overall response per investigator assessment based on the T-PLL consensus criteria 2019. Stable disease is defined as meeting all of the following criteria for at least 3 months:
|
Clinical response was assessed at Weeks 4, 8, 12, 16, and 24 for DCR assessment
|
Overall Survival (OS)
Time Frame: From first dose of study drug to end of study; median time on study was 30.1 weeks.
|
Overall survival is defined as the time from the date of the participant's first dose of any study drug to death from any cause.
OS was calculated using Kaplan-Meier methods.
|
From first dose of study drug to end of study; median time on study was 30.1 weeks.
|
Number of Eligible Participants Reaching Autologous or Allogeneic Transplantation
Time Frame: From first dose of study drug to end of study; median time on study was 30.1 weeks.
|
Participants eligible for autologous or allogeneic transplantation were transplant-naïve participants who achieved CR.
|
From first dose of study drug to end of study; median time on study was 30.1 weeks.
|
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Time Frame: From first dose of study drug up to 30 days after last dose; median time on treatment was 13.86 weeks (range 1.0 to 44.4 weeks)
|
An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Treatment-emergent AEs are any event with onset after the first dose of study drug and no more than 30 days after the last dose of study drug. A serious AE was an event that resulted in death, was life-threatening, resulted in hospitalization or prolongation of hospitalization, persistent or significant disability/incapacity, or an important medical event requiring medical or surgical intervention to prevent a serious outcome. The Investigator rated the severity of each AE according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening and grade 5 = death. The Investigator assessed the relationship of the AE to the use of study drug. |
From first dose of study drug up to 30 days after last dose; median time on treatment was 13.86 weeks (range 1.0 to 44.4 weeks)
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- M18-803
- 2018-002179-17 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Clinical Study Report (CSR)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Leukemia
-
Massachusetts General HospitalCelgene CorporationTerminatedAcute Myelogenous Leukemia | Acute Myeloid Leukemia (AML) | Acute Myelocytic Leukemia | Acute Granulocytic Leukemia | Acute Non-Lymphocytic LeukemiaUnited States
-
Institute of Hematology & Blood Diseases HospitalBejing Institute for Stem Cell and Regenerative Medicine; Institute for Stem...RecruitingRefractory Leukemia | Relapsed Leukemia | Acute Myeloid Leukemia, ChildhoodChina
-
Stanford UniversityTerminatedLeukemia | Leukemia, Lymphocytic, Acute | Leukemia Acute Promyelocytic Leukemia (APL) | Leukemia Acute Lymphoid Leukemia (ALL) | Leukemia Chronic Myelogenous Leukemia (CML) | Leukemia Acute Myeloid Leukemia (AML) | Leukemia Chronic Lymphocytic Leukemia (CLL)United States
-
Betta Pharmaceuticals Co., Ltd.Not yet recruitingAcute Myeloid Leukemia LeukemiaChina
-
Center for International Blood and Marrow Transplant...National Marrow Donor Program; St. Baldrick's FoundationActive, not recruitingAcute Myelogenous LeukemiaUnited States
-
Massachusetts General HospitalCompleted
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Monoblastic Leukemia (M5a) | Childhood Acute Monocytic Leukemia (M5b) | Childhood Acute Myeloblastic Leukemia Without Maturation (M1) | Childhood Acute Myelomonocytic Leukemia (M4) | Childhood Acute Myeloid Leukemia/Other Myeloid MalignanciesUnited States
-
Hybrigenics CorporationUnknownAcute Myelogenous LeukemiaUnited States, France
-
National Cancer Institute (NCI)TerminatedAdult Acute Megakaryoblastic Leukemia (M7) | Adult Acute Minimally Differentiated Myeloid Leukemia (M0) | Adult Acute Monoblastic Leukemia (M5a) | Adult Acute Monocytic Leukemia (M5b) | Adult Acute Myeloblastic Leukemia With Maturation (M2) | Adult Acute Myeloblastic Leukemia Without Maturation... and other conditionsUnited States
-
University of PennsylvaniaActive, not recruitingAcute Myeloid Leukemia, in Relapse | Acute Myeloid Leukemia, Refractory | Acute Myeloid Leukemia, PediatricUnited States
Clinical Trials on Venetoclax
-
Virginia Commonwealth UniversityAbbVieWithdrawnRelapsed Small Cell Lung Cancer | Refractory Small Cell Lung Carcinoma
-
PrECOG, LLC.Genentech, Inc.CompletedFollicular Lymphoma | Non-Hodgkin's Lymphoma Follicular | Non-Hodgkin's Lymphoma, Adult High GradeUnited States
-
University of Maryland, BaltimoreActive, not recruitingRelapsed or Refractory Acute Myeloid LeukemiaUnited States
-
Yale UniversityCompleted
-
Gruppo Italiano Malattie EMatologiche dell'AdultoRecruiting
-
Stichting Hemato-Oncologie voor Volwassenen NederlandNordic Lymphoma GroupActive, not recruiting
-
The Lymphoma Academic Research OrganisationInstitute of Cancer Research, United KingdomRecruitingMantle Cell LymphomaFrance, United Kingdom, Belgium
-
Stichting Hemato-Oncologie voor Volwassenen NederlandNordic CLL Study GroupActive, not recruitingChronic Lymphocytic Leukemia in Relapse | Chronic Lymphocytic Leukemia in RemissionNetherlands, Belgium, Denmark, Finland, Norway, Sweden
-
National Heart, Lung, and Blood Institute (NHLBI)RecruitingChronic Lymphocytic LeukemiaUnited States
-
BioSight Ltd.Recruiting