Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
M16-788
- NCT ID:
NCT03406156
Conditions
- Chronic Lymphocytic Leukemia (CLL)
- Small Lymphocytic Lymphoma (SLL)
Interventions
| Drug | Synonyms | Arms |
|---|
| Obinutuzumab | Gazyva | Obinutuzumab +/- bendamustine then obinutuzumab + venetoclax |
| Bendamustine | Bendeka | Obinutuzumab +/- bendamustine then obinutuzumab + venetoclax |
| Venetoclax | Venclexta, ABT-199, GDC-0199 | Obinutuzumab +/- bendamustine then obinutuzumab + venetoclax |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Obinutuzumab +/- bendamustine then obinutuzumab + venetoclax | Experimental | 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. | - Obinutuzumab
- Bendamustine
- Venetoclax
|
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 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.
| Maximum Eligible Age: | 99 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Percent of Participants Achieving Low Tumor Burden Status with induction of Obinutuzumab or Obinutuzumab plus Bendamustine (Debulking Period) |
| Time Frame: | Up to approximately 24 weeks after initial dose of study drug |
| Safety Issue: | |
| Description: | Low tumor burden is defined by peripheral lymphocyte counts of < 25,000 and all lymph nodes < 5 cm per CT scans. |
Secondary Outcome Measures
| Measure: | Overall Response Rate (ORR) |
| Time Frame: | Up to approximately 3.5 years after initial dose of study drug |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Duration of Response (DoR) |
| Time Frame: | Up to approximately 3.5 years after initial dose of study drug |
| Safety Issue: | |
| Description: | 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). |
| Measure: | Progression-Free Survival (PFS) |
| Time Frame: | Up to approximately 3.5 years after initial dose of study drug |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Time to Progression (TTP) |
| Time Frame: | Up to approximately 3.5 years after initial dose of study drug |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Overall Survival (OS) |
| Time Frame: | Up to approximately 3.5 years after initial dose of study drug |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Undetectable Minimal Residual Disease (UMRD) Rate |
| Time Frame: | Up to approximately 3.5 years after initial dose of study drug |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | AbbVie |
Trial Keywords
- Cancer
- Chronic Lymphocytic Leukemia
- 17p Deletion
- debulking
- obinutuzumab
- bendamustine
- tumor lysis syndrome
- venetoclax
- Small Lymphocytic Lymphoma
Last Updated
July 2, 2021
