A Study in Previously Untreated Chronic Lymphocytic Leukemia (CLL) Subjects, Excluding Those With the 17p Deletion, to Evaluate Debulking Regimens Prior to Initiating Venetoclax Combination Therapy

Sponsor

AbbVie (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03406156

Collaborator

(none)

120

Enrollment

Locations

Arm

59.3

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A study in previously untreated Chronic Lymphocytic Leukemia participants to evaluate alternate administration strategies for induction therapy (debulking) with obinutuzumab or obinutuzumab/bendamustine prior to combination therapy with obinutuzumab and venetoclax.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia (CLL) Small Lymphocytic Lymphoma (SLL)	Drug: Obinutuzumab Drug: Bendamustine Drug: Venetoclax	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3b Study in Previously Untreated Chronic Lymphocytic Leukemia (CLL) Subjects, Excluding Those With the 17p Deletion, to Evaluate Debulking Regimens Prior to Initiating Venetoclax Combination Therapy

Actual Study Start Date :

Aug 10, 2018

Actual Primary Completion Date :

Oct 12, 2021

Anticipated Study Completion Date :

Jul 19, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Obinutuzumab +/- bendamustine then obinutuzumab + venetoclax Debulking Period: Obinutuzumab with or without bendamustine (bendamustine administered in participants with high tumor load as described in the protocol) during the debulking period (up to 6 cycles). Treatment Period: Venetoclax + obinutuzumab regimen initiated when participant achieves low tumor burden during debulking period, or if the participant has not achieved low tumor burden status after 6 cycles of debulking, the participant may proceed to venetoclax per the discretion of the treating provider after discussion with the study physician. During this regimen period, participants to receive obinutuzumab in combination with venetoclax for 5 months then venetoclax therapy alone to continue for a total duration of up to 53 weeks.	Drug: Obinutuzumab intravenous Other Names: Gazyva Drug: Bendamustine intravenous Other Names: Bendeka Drug: Venetoclax tablet Other Names: Venclexta ABT-199 GDC-0199

Arm

Intervention/Treatment

Experimental: Obinutuzumab +/- bendamustine then obinutuzumab + venetoclax

Debulking Period: Obinutuzumab with or without bendamustine (bendamustine administered in participants with high tumor load as described in the protocol) during the debulking period (up to 6 cycles). Treatment Period: Venetoclax + obinutuzumab regimen initiated when participant achieves low tumor burden during debulking period, or if the participant has not achieved low tumor burden status after 6 cycles of debulking, the participant may proceed to venetoclax per the discretion of the treating provider after discussion with the study physician. During this regimen period, participants to receive obinutuzumab in combination with venetoclax for 5 months then venetoclax therapy alone to continue for a total duration of up to 53 weeks.

Drug: Obinutuzumab

intravenous

Other Names:

Gazyva

Drug: Bendamustine

intravenous

Other Names:

Bendeka

Drug: Venetoclax

tablet

Other Names:

Venclexta

ABT-199

GDC-0199

Outcome Measures

Primary Outcome Measures

Percent of Participants Achieving Low Tumor Burden Status with induction of Obinutuzumab or Obinutuzumab plus Bendamustine (Debulking Period) [Up to approximately 24 weeks after initial dose of study drug]
Low tumor burden is defined by peripheral lymphocyte counts of < 25,000 and all lymph nodes < 5 cm per CT scans.
Complete Remission Rate (CR) and Complete Remission with Incomplete Marrow Recovery (CRi) [Up to approximately 65 weeks after initial dose of venetoclax]
Defined as the proportion of subjects who achieved CR or CRi (per the 2008 Modified International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-sponsored Working Group [IWCLL NCI-WG] criteria).

Secondary Outcome Measures

Overall Response Rate (ORR) [Up to approximately 3.5 years after initial dose of study drug]
ORR is defined as the proportion of participants with an overall response (CR, CRi, nodular partial remission [nPR] plus partial remission [PR]) per the 2008 Modified IWCLL NCI-WG criteria.
Duration of Response (DoR) [Up to approximately 3.5 years after initial dose of study drug]
DOR defined as the number of days from the date of first response (CR, CRi, nPR, or PR) (per the 2008 Modified IWCLL NCI-WG criteria) to the date of disease progression or death. All disease progression will be included regardless whether the event occurred during or after the participant was taking any study drug (either venetoclax, obinutuzumab, or bendamustine).
Progression-Free Survival (PFS) [Up to approximately 3.5 years after initial dose of study drug]
PFS is defined as the number of days from the date of first dose of any study drug (either venetoclax, obinutuzumab, or bendamustine) to the date of disease progression or death, whichever occurs first. All disease progression will be included regardless whether the event occurred during or after the participant was taking any study drug.
Time to Progression (TTP) [Up to approximately 3.5 years after initial dose of study drug]
TPP is defined as the number of days from the date of first dose of any study drug (either venetoclax, obinutuzumab, or bendamustine) to date of disease progression. All disease progression will be included regardless whether the event occurred during or after the participant was taking any study drug.
Overall Survival (OS) [Up to approximately 3.5 years after initial dose of study drug]
OS is defined as number of days from the date of first dose of any study drug (either venetoclax, obinutuzumab, or bendamustine) to the date of death.
Undetectable Minimal Residual Disease (UMRD) Rate [Up to approximately 3.5 years after initial dose of study drug]
UMRD defined as less than one CLL cell per 10,000 leukocytes (or below 10^-4). Rate of UMRD status will be defined as the percentage of participants who have UMRD.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adequate hematology, kidney and liver function as described in the protocol.
Diagnosis of previously untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) according to 2008 Modified International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-sponsored Working Group (IWCLL NCI-WG) criteria.
Eastern Cooperative Oncology Group (ECOG) performance score of 0 - 1.
CLL requires treatment according to the IWCLL criteria.
Medium tumor burden (any lymph node [LN] 5 to < 10 cm OR absolute lymphocyte count [ALC] >= 25 × 10^{9/L) OR High tumor burden (any LN >= 10 cm OR ALC >= 25 × 10}9/L and LN >= 5 cm).

Exclusion Criteria:

Presence of 17p deletion at Screening.
Richter's syndrome (transformation of CLL/SLL to aggressive non-Hodgkin's lymphoma or Hodgkin's lymphoma).
Prolymphocytic leukemia.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates, PC-HOPE /ID# 202335	Tempe	Arizona	United States	85284-1812
2	Rocky Mountain Cancer Centers - Denver Midtown /ID# 202328	Denver	Colorado	United States	80218
3	MidAmerica Division, Inc. /ID# 201099	Kansas City	Missouri	United States	64132
4	Oncology Hematology Care, Inc - Kenwood /ID# 202397	Cincinnati	Ohio	United States	45236-2725
5	Willamette Valley Cancer Institute /ID# 201201	Eugene	Oregon	United States	97401-6043
6	Prisma Health Cancer Inst - Eastside /ID# 202329	Greenville	South Carolina	United States	29615
7	Tennessee Oncology - Chattanooga /ID# 202840	Chattanooga	Tennessee	United States	37404-1108
8	Tennessee Oncology-Nashville Centennial /ID# 201098	Nashville	Tennessee	United States	37203-1632
9	Texas Oncology - Austin Midtown /ID# 201199	Austin	Texas	United States	78705
10	Texas Oncology - Beaumont /ID# 202359	Beaumont	Texas	United States	77701-4691
11	Texas Oncology - Medical City Dallas /ID# 201196	Dallas	Texas	United States	75230
12	Texas Oncology - McAllen /ID# 202331	McAllen	Texas	United States	78503
13	Texas Oncology - San Antonio Medical Center /ID# 202332	San Antonio	Texas	United States	78240-5251
14	Texas Oncology - Tyler /ID# 201211	Tyler	Texas	United States	75702
15	Northwest Cancer Specialists, P.C. /ID# 201198	Vancouver	Washington	United States	98684