A Study Evaluating the Efficacy of Venetoclax Plus Ibrutinib in Participants With T-cell Prolymphocytic Leukemia

Cancer Clinical Trial

Official title:

A Prospective, Open-Label, Single-Arm, Phase 2, Multicenter Study Evaluating the Efficacy of Venetoclax Plus Ibrutinib in Subjects With T-Cell Prolymphocytic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03873493
• Other study ID #: M18-803
• Secondary ID: 2018-002179-17
• Status: Completed
• Phase: Phase 2
• Start date: January 14, 2020
• Est. completion date: November 4, 2021

Study information

• Verified date: November 2022
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective of this study is to evaluate the efficacy of the combination of venetoclax plus ibrutinib for treating adults with T-cell prolymphocytic leukemia (T-PLL).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: November 4, 2021
• Est. primary completion date: November 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cancer
• Leukemia
• Leukemia, Prolymphocytic
• Leukemia, Prolymphocytic, T-Cell
• T-cell Prolymphocytic Leukemia (T-PLL)

Intervention

Drug:
• Venetoclax
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.
• Ibrutinib
Ibrutinib capsules taken orally once a day, 420 mg/day until the end-of-treatment.

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Ctr /ID# 209554	Melbourne	Victoria
Austria	Medizinische Universitaet Wien /ID# 208497	Vienna	Wien
Finland	Helsinki University Hospital /ID# 208108	Helsinki	Uusimaa
France	CHRU Lille - Hopital Claude Huriez /ID# 208726	Lille	Hauts-de-France
France	Hopital Pitie Salpetriere /ID# 208730	Paris
France	HCL - Hôpital Lyon Sud /ID# 208731	Pierre Benite CEDEX	Auvergne-Rhone-Alpes
Germany	University Hospital Cologne /ID# 208834	Cologne
Italy	Azienda Sanitaria Universitaria Giuliano Isontina /ID# 211487	Trieste
Netherlands	Maxima Medisch Centrum /ID# 207989	Eindhoven
Netherlands	Universitair Medisch Centrum Groningen /ID# 207990	Groningen
United Kingdom	The Royal Marsden NHS Foundation Trust /ID# 211263	London
United Kingdom	Oxford University Hospitals NHS Foundation Trust /ID# 211264	Oxford	Oxfordshire
United States	Dana-Farber Cancer Institute /ID# 207728	Boston	Massachusetts
United States	University of Texas MD Anderson Cancer Center /ID# 207746	Houston	Texas
United States	Mayo Clinic - Rochester /ID# 207692	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Finland,  France,  Germany,  Italy,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	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: all lymph nodes < 1 cm; spleen < 13 cm; no constitutional symptoms; circulating lymphocyte count < 4 × 10^9/L; bone marrow T-PLL cells < 5% of mononuclear cells; no other specific site involvement; Group B: platelets = 100 × 10^9 /L; hemoglobin = 11.0 g/dL; neutrophils = 1.5 × 10^9 /L.; 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	Progression-Free Survival (PFS)	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: lymph nodes increase in > 20% in sum of long-axis diameters of up to 3 target lesions (SLD) from nadir; spleen increase = 50% in vertical length beyond normal from baseline; circulating lymphocyte count increase = 50% from baseline; appearance of a new lesion; Group B: platelet count decrease of = 50% from baseline due to T-PLL (not due to drug toxicity); hemoglobin decrease of = 2 g/dL from baseline due to T-PLL; neutrophils decrease of = 50% from baseline due to T-PLL.	From first dose of study drug to end of study; median time on study was 30.1 weeks.
Secondary	Duration of Response (DOR)	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: lymph nodes increase in > 20% in SLD from nadir; spleen increase = 50% in vertical length beyond normal from baseline; circulating lymphocyte count increase = 50% from baseline; appearance of a new lesion; Group B: platelet count decrease of = 50% from baseline due to T-PLL (not due to drug toxicity); hemoglobin decrease of = 2 g/dL from baseline due to T-PLL; neutrophils decrease of = 50% from baseline due to T-PLL.	From first dose of study drug to end of study; median time on study was 30.1 weeks.
Secondary	Time to Progression (TTP)	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: lymph nodes increase in > 20% in SLD from nadir; spleen increase = 50% in vertical length beyond normal from baseline; circulating lymphocyte count increase = 50% from baseline; appearance of a new lesion; Group B: platelet count decrease of = 50% from baseline due to T-PLL (not due to drug toxicity); hemoglobin decrease of = 2 g/dL from baseline due to T-PLL; neutrophils decrease of = 50% from baseline due to T-PLL.	From first dose of study drug to end of study; median time on study was 30.1 weeks.
Secondary	Event-free Survival (EFS)	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: lymph nodes increase in > 20% in SLD from nadir; spleen increase = 50% in vertical length beyond normal from baseline; circulating lymphocyte count increase = 50% from baseline; appearance of a new lesion; Group B: platelet count decrease of = 50% from baseline due to T-PLL (not due to drug toxicity); hemoglobin decrease of = 2 g/dL from baseline due to T-PLL; neutrophils decrease of = 50% from baseline due to T-PLL.	From first dose of study drug to end of study; median time on study was 30.1 weeks.
Secondary	Disease Control Rate (DCR)	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: lymph nodes change of -29% to +20% in SLD; spleen change of -49% to +49% beyond normal from baseline; circulating lymphocyte count > 30 × 10^9 /L or change of -49% to +49%; platelet count change of -49% to +49%; hemoglobin < 11.0 g/dL or change < 50% from baseline or change < 2 g/dL; neutrophils change of -49% to +49%.	Clinical response was assessed at Weeks 4, 8, 12, 16, and 24 for DCR assessment
Secondary	Overall Survival (OS)	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.
Secondary	Number of Eligible Participants Reaching Autologous or Allogeneic Transplantation	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.
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAE)	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)

External Links

•   This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.