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

Chronic Lymphocytic Leukemia (CLL) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03406156
• Other study ID #: M16-788
• Status: Completed
• Phase: Phase 3
• Start date: August 10, 2018
• Est. completion date: July 10, 2023

Study information

• Verified date: January 2024
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: July 10, 2023
• Est. primary completion date: October 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia (CLL)
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Small Lymphocytic Lymphoma (SLL)

Intervention

Drug:
• Obinutuzumab
Administered via intravenous infusion
• Bendamustine
Administered via intravenous infusion
• Venetoclax
The venetoclax dose was administered according to a weekly ramp-up schedule over 5 weeks to the recommended daily dose of 400 mg. Participants were instructed to take venetoclax tablets with a meal and water at approximately the same time each day. Venetoclax tablets were to be swallowed whole and not chewed, crushed, or broken prior to swallowing.

Locations

Country	Name	City	State
United States	Texas Oncology - Austin Midtown /ID# 201199	Austin	Texas
United States	Texas Oncology - Beaumont /ID# 202359	Beaumont	Texas
United States	Tennessee Oncology - Chattanooga /ID# 202840	Chattanooga	Tennessee
United States	Oncology Hematology Care, Inc. /ID# 202397	Cincinnati	Ohio
United States	Texas Oncology - Medical City Dallas /ID# 201196	Dallas	Texas
United States	Rocky Mountain Cancer Centers - Denver Midtown /ID# 202328	Denver	Colorado
United States	Willamette Valley Cancer Institute and Research Center /ID# 201201	Eugene	Oregon
United States	Prisma Health Cancer Inst - Eastside /ID# 202329	Greenville	South Carolina
United States	MidAmerica Division, Inc. /ID# 201099	Kansas City	Missouri
United States	Texas Oncology - McAllen /ID# 202331	McAllen	Texas
United States	Tennessee Oncology-Nashville Centennial /ID# 201098	Nashville	Tennessee
United States	Texas Oncology - San Antonio Medical Center /ID# 202332	San Antonio	Texas
United States	Arizona Oncology Associates, PC-HOPE /ID# 202335	Tempe	Arizona
United States	Texas Oncology - Northeast Texas /ID# 201211	Tyler	Texas
United States	Northwest Cancer Specialists, P.C. /ID# 201198	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

United States, 

References & Publications (6)

Chyla B, Jiang D, Pesko J, Courtright J, Sharman J, Andorsky D, et al. 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 M

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 U

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 p

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

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

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Low Tumor Burden Status With Induction of Obinutuzumab or Obinutuzumab Plus Bendamustine (Debulking Period)	Low tumor burden is defined as absolute lymphocyte count (ALC) < 25 × 10^9 /L and all lymph nodes < 5 cm per computed tomography (CT) scans.	From Baseline to the end of Cycles 2, 4, and 6, up to approximately 24 weeks after initial dose of study drug
Primary	Complete Response Rate	Complete response rate is defined as the percentage of participants achieving complete remission (CR) or complete remission with incomplete marrow recovery (CRi) as their best response based on 2008 Modified International Workshop for Chronic Lymphocytic Leukemia National Cancer Institute-Working Group (IWCLL NCI-WG) criteria.; CR required all of the following: Peripheral blood lymphocytes <4000/µL; Absence of lymphadenopathy by physical examination and computed tomography scan; No hepatomegaly or splenomegaly by physical examination; Absence of disease or constitutional symptoms (unexplained fevers >38°C, drenching night sweats, =10% weight loss in last 6 months); Blood counts above the following: Neutrophils >1500/µL; Platelets >100,000/µL; Hemoglobin >11.0 g/dL; Bone marrow at least normocellular for age, <30% lymphocytes; CRi was defined as participants with CR who had persistent cytopenia unrelated to CLL but related to drug toxicity.	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	Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieved a best response of complete remission (CR), complete remission with incomplete marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) based on the 2008 Modified IWCLL NCI-WG criteria at any time during the study as assessed by investigator up through the completion of the 65-week disease response assessment after the start of venetoclax. Participants who did not respond were considered non-responders.	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	Duration of Response (DoR)	DoR is 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, whichever occurs first. All disease progression was to be included regardless whether the event occurred during or after the participant was taking any study drug (either venetoclax, obinutuzumab, or bendamustine). Duration of response was analyzed by Kaplan-Meier (K-M) methodology.	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	Progression-Free Survival (PFS)	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 was to be included regardless whether the event occurred during or after the participant was taking any study drug. Progression-free survival was analyzed by Kaplan-Meier methodology.	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	Time to Progression (TTP)	TTP 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 was to be included regardless of whether the event occurred during or after the participant was taking any study drug.The distribution of the time to progression was estimated using Kaplan-Meier methodology.	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	Overall Survival (OS)	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. If a participant had not died, their data was censored at the date when they were last known to be alive prior to the cutoff date.The distribution of OS was estimated using Kaplan-Meier methodology.	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	Undetectable Minimal Residual Disease (UMRD) Rate	The level of MRD was assessed in the peripheral blood of all participants at 5 months after last dose of obinutuzumab, and at 3 months after last dose of venetoclax/end of treatment (including early study termination) to determine the rate of UMRD. Undetectable Minimal Residual Disease is defined as less than one CLL cell per 10,000 leukocytes (< 10^-4 ).	From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021)

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