Clinical trial NCT03406156: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Keywords: Cancer
Chronic Lymphocytic Leukemia
17p Deletion
Debulking
Obinutuzumab
Bendamustine
Tumor lysis syndrome
Venetoclax
Small Lymphocytic Lymphoma
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2018-01-23
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-cohort, open-label study in previously untreated participants with chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), excluding those with the 17p deletion, to evaluate a debulking strategy that would enable all participants to receive subsequent venetoclax as outpatients, with lower risk of tumor lysis syndrome.

Detailed description: Safety and efficacy data through 13 October 2021 are included in the interim analysis, which was conducted after all participants completed the post-treatment Week 65 visit or discontinued from the study.

Eligibility criteria: 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/SLL 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

Primary outcomes:
measure: Percentage of Participants Achieving Low Tumor Burden Status With Induction of Obinutuzumab or Obinutuzumab Plus Bendamustine (Debulking Period)
timeFrame: From Baseline to the end of Cycles 2, 4, and 6, up to approximately 24 weeks after initial dose of study drug
measure: Complete Remission Rate
timeFrame: From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021); overall median time on follow-up was up to 787 days
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021); overall median time on follow-up was up to 787 days
measure: Duration of Response (DoR)
timeFrame: From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021); overall median time on follow-up was up to 787 days
measure: Progression-Free Survival (PFS)
timeFrame: From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021); overall median time on follow-up was up to 787 days
measure: Time to Progression (TTP)
timeFrame: From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021); overall median time on follow-up was up to 787 days
measure: Overall Survival (OS)
timeFrame: From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021); overall median time on follow-up was up to 787 days
measure: Undetectable Minimal Residual Disease (UMRD) Rate
timeFrame: From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021)
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Arizona Oncology Associates, PC-HOPE /ID# 202335
state: Arizona
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers - Denver Midtown /ID# 202328
state: Colorado
city: Kansas City
country: United States
facility: MidAmerica Division, Inc. /ID# 201099
state: Missouri
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc. /ID# 202397
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center /ID# 201201
state: Oregon
city: Greenville
country: United States
facility: Prisma Health Cancer Inst - Eastside /ID# 202329
state: South Carolina
city: Chattanooga
country: United States
facility: Tennessee Oncology - Chattanooga /ID# 202840
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology-Nashville Centennial /ID# 201098
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown /ID# 201199
state: Texas
city: Beaumont
country: United States
facility: Texas Oncology - Beaumont /ID# 202359
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Medical City Dallas /ID# 201196
state: Texas
city: McAllen
country: United States
facility: Texas Oncology - McAllen /ID# 202331
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Medical Center /ID# 202332
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Northeast Texas /ID# 201211
state: Texas
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C. /ID# 201198
state: Washington
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
citation: Flinn IW, Andorsky D, Melear J, Manda S, Anz B III, Kolibaba K, Yimer H, Burke JM, Fanning S, Courtright J, Islas-Ohlmayer M, Kambhampati S, Vizkelety T, Pesko J, Chyla B, Jiang D, Sharman JP. Debulking Before Initiation of Venetoclax Therapy in Untreated Patients with Chronic Lymphocytic Leukemia: Results from a Phase 3b Study. American Society of Hematology - 63rd Annual Meeting. 2021
citation: Sharman J, Andorsky D, Melear J, Manda S, Anz B III, Kolibaba K, Yimer H, Burke J, Fanning S, Courtright J, Islas-Ohlmayer M, Kambhampati S, Jiang D, Pesko D, Vizkelety T, Sharmokh S, Nielsen J, Flinn I. Phase 3b study to evaluate debulking regimens prior to initiating venetoclax therapy in untreated patients with chronic lymphocytic leukemia. Florida Society of Clinical Oncology-2020 Fall Session
citation: Flinn I, Andorsky D, Melear J, Manda S, Anz B III, Kolibaba K, Yimer H, Burke J, Fanning S, Courtright J, Islas-Ohlmayer M, Kambhampati S, Jiang D, Pesko D, Vizkelety T, Sharmokh S, Sharman J. Debulking Regimens Prior To Initiating Venetoclax Therapy in Untreated Patients with Chronic Lymphocytic Leukemia: Interim Results from a Phase 3b Study. American Society of Hematology - 62nd Annual Meeting. 2020
citation: Sharman J, Andorsky D, Melear J, Manda S, Anz B III, Kolibaba K, Yimer H, Burke J, Fanning S, Courtright J, Islas-Ohlmayer M, Kambhampati S, Jiang D, Pesko J, Vizkelety T, Sharmokh S, Nielsen J, Flinn I. Phase 3b Study to Evaluate Debulking Regimens Prior to Initiating Venetoclax Therapy in Untreated Patients with Chronic Lymphocytic Leukemia. Society of Hematologic Oncology-8th Annual Meeting. 2020
citation: Sharman J, Andorsky D. Melear J, Manda S, Anz B II, Kolibaba K, Yimer H, Burke J, Fanning S, Courtright J, Islas-Ohlmayer M, Kambhampati S, Jiang D, Pesko J, Vizkelety T, Sharmkokh S, Nielsen J, Flinn I. Phase 3b study to evaluate debulking regimens prior to initiating venetoclax therapy in untreated patients with chronic lymphocytic leukemia. European Hematology Association-25th Congress. 2020
citation: Sharman J, Andorsky D, Melear J, Manda S, Anz B III, Kolibaba K, Yimer H, Burke J, Fanning S, Courtright J, Islas-Ohlmayer M, Kambhampati S, Al Masud A, Zimmerman T, Nielsen J, Vizkelety T, Jiang D, Flinn I. Debulking eliminates need for hospitalization prior to initiating frontline venetoclax therapy in previously untreated CLL patients: a phase 3b study. American Society of Hematology - 61st Annual Meeting. 2019