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

Sponsor

AbbVie (Industry)

Overall Status

Completed

CT.gov ID

NCT03873493

Collaborator

(none)

Enrollment

Locations

Arm

21.7

Actual Duration (Months)

0.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A study to evaluate the safety and efficacy of venetoclax plus ibrutinib for participants with T-cell Prolymphocytic Leukemia (T-PLL) and follows a 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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia T-cell Prolymphocytic Leukemia (T-PLL) Cancer	Drug: Venetoclax Drug: Ibrutinib	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 14, 2020

Actual Primary Completion Date :

Nov 4, 2021

Actual Study Completion Date :

Nov 4, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Venetoclax + Ibrutinib Venetoclax at a predetermined dose according to a prescribed dosing schedule orally once daily (QD) plus Ibrutinib Dose A orally QD.	Drug: Venetoclax tablet; oral Other Names: ABT-199 GDC-0199 Venclexta Venclyxto Drug: Ibrutinib capsule; oral Other Names: Imbruvica

Arm

Intervention/Treatment

Experimental: Venetoclax + Ibrutinib

Venetoclax at a predetermined dose according to a prescribed dosing schedule orally once daily (QD) plus Ibrutinib Dose A orally QD.

Drug: Venetoclax

tablet; oral

Other Names:

ABT-199

GDC-0199

Venclexta

Venclyxto

Drug: Ibrutinib

capsule; oral

Other Names:

Imbruvica

Outcome Measures

Primary Outcome Measures

Overall Response Rate (ORR) [Up to approximately 2 years]
ORR is defined as the percentage of participants achieving complete remission (CR), CR with incomplete bone marrow recovery (CRi), or partial response (PR) as their best response (per investigator assessment).

Secondary Outcome Measures

Progression-Free Survival (PFS) [Up to approximately 2 years]
PFS is defined as the time from the date of first dose of any study drug to the date of earliest disease progression or death.
Duration of Response (DOR) [Up to approximately 2 years]
DOR defined for participants who achieve 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.
Time to Progression (TTP) [Up to approximately 2 years]
TPP 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.
Event-free Survival (EFS) [Up to approximately 2 years]
EFS 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.
Disease Control Rate (DCR) [Up to approximately 2 years]
DCR defined as the percentage of participants achieving CR, CRi, PR, or stable disease as best overall response.
Overall Survival (OS) Rate [Up to approximately 2 years]
OS is defined as the time from the date of the participant's first dose of any study drug to death from any cause.
Number of Eligible Participants Reaching Autologous or Allogeneic Transplantation [Up to approximately 2 years]
Number of eligible participants reaching autologous or allogeneic transplantation.
Number of Participants with Adverse Events (AE) [Up to approximately 2 years]
AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber Cancer Institute /ID# 207728	Boston	Massachusetts	United States	02215
2	Mayo Clinic - Rochester /ID# 207692	Rochester	Minnesota	United States	55905-0001
3	University of Texas MD Anderson Cancer Center /ID# 207746	Houston	Texas	United States	77030
4	Peter MacCallum Cancer Ctr /ID# 209554	Melbourne	Victoria	Australia	3000
5	Medizinische Universitaet Wien /ID# 208497	Vienna	Wien	Austria	1090
6	Helsinki University Hospital /ID# 208108	Helsinki	Uusimaa	Finland	00290
7	HCL - Hôpital Lyon Sud /ID# 208731	Pierre Benite CEDEX	Auvergne-Rhone-Alpes	France	69495
8	CHRU Lille - Hopital Claude Huriez /ID# 208726	Lille	Hauts-de-France	France	59037
9	Hopital Pitie Salpetriere /ID# 208730	Paris		France	75013
10	University Hospital Cologne /ID# 208834	Cologne		Germany	50937
11	Azienda Sanitaria Universitaria Giuliano Isontina /ID# 211487	Trieste		Italy	34128
12	Maxima Medisch Centrum /ID# 207989	Eindhoven		Netherlands	5631 BM
13	Universitair Medisch Centrum Groningen /ID# 207990	Groningen		Netherlands	9713 GZ
14	Oxford University Hospitals NHS Foundation Trust /ID# 211264	Oxford	Oxfordshire	United Kingdom	OX3 9DU
15	The Royal Marsden NHS Foundation Trust /ID# 211263	London		United Kingdom	SW3 6JJ