Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Recurrence

Leukemia

Leukemia, Lymphoid

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Disease Attributes

Leukemia, B-Cell

Chronic Disease

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Venetoclax

Ibrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive ibrutinib PO QD beginning on week 1 day 1. Treatment with ibrutinib continues in the absence of disease progression or unacceptable toxicity. Patients also receive venetoclax PO QD beginning on week 9 day 1. Treatment with venetoclax continues up to week 61 day 7 in the absence of disease progression or unacceptable toxicity.

Administered at 420 mg/day, as oral capsules (3 x 140 mg), starting Day 1, Week 1.

Administered as tablets, starting Day 1, Week 9, with dose increasing every 7 days through 5 dose levels (20 mg; 50 mg; 100 mg; 200 mg; 400 mg).

Steven Coutre

This is an open-label non-randomized two-center phase 2 study evaluating the safety and efficacy of concurrent therapy with ibrutinib and venetoclax in subjects with relapsed or refractory CLL/SLL.

The primary objective of this study is to evaluate the efficacy of concurrent therapy with ibrutinib and venetoclax in patients with relapsed and refractory chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL).

The secondary objectives of this study are to define the safety, tolerability, and dose-limiting toxicity (DLT) within 28 days of completion of dose-escalation.

Venetoclax and Ibrutinib in Patients With Relapsed/Refractory CLL or SLL

An Open Label Phase 2 Trial of Venetoclax With Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

The time-to-next-treatment (TTNT) is a measure of the period of time from the beginning of treatment until the patient has to receive a different treatment for his/her disease. TTNT was assessed as the time period until the participants next anti-chronic lymphocytic leukemia (CLL) treatment.

The outcome will be reported as the median TTNT as determined by Kaplan-Meier methodology, with 95% confidence interval (95% CI).

Complete Response (CR) will be assessed as the number of participants who, based on investigator assessment based on the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria, achieve a complete remission. IWCLL complete remission is defined as follows.

* Lymphadenopathy: none \> 1.5 cm
* Blood lymphocytes: \< 4,000/µL
* Hepatomegaly: none
* Splenomegaly: none
* Bone marrow: normocellular with \< 30 lymphocytes, no B lymphoid nodules.

The outcome is reported as the number of participants who achieve CR, a number without dispersion.

Duration of response (DoR) refers to a participant maintaining clinical response after achieving either complete response (CR) or partial response (PR). The outcome is reported as the number of subjects who have maintained clinical response through 117 weeks. Response defined as the following.

CR.

* Lymphadenopathy: none \> 1.5 cm
* Blood lymphocytes: \< 4,000/µL
* Hepatomegaly: none
* Splenomegaly: none
* Bone marrow: normocellular with \< 30 lymphocytes, no B lymphoid nodules. PR.
* Lymphadenopathy: decrease ≥ 50%
* Blood lymphocytes: decrease ≥ 50%
* Hepatomegaly: decrease ≥ 50%
* Splenomegaly: decrease ≥ 50%
* Bone marrow: not considered.

Minimal residual disease (MRD) refers to the small numbers of leukemic cells that can remain in the participant after treatment, and may not be associated with any symptoms (remission). Although the participant may feel "healthy," the MRD is a major cause of eventual leukemic relapse. "MRD-negative" is the ideal treatment outcome. MRD negativity was defined as less than one leukemic cell per 10,000 leukocytes as assessed by bone marrow-based flow cytometry. The outcome is reported as the number of participants who were positive for MRD, or negative.

Overall response (OR) is the overall number of subjects that begin treatment and achieve a complete response (CR); partial response (PR); or Stable Disease (SD) 62 weeks after the beginning of treatment, according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria. IWCLL CR is defined as follows. The outcome is reported as the number of participants who achieve CR, PR, or SD, and number without dispersion.

CR:

* Lymphadenopathy: none \> 1.5 cm
* Blood lymphocytes: \< 4,000/µL
* Hepatomegaly: none
* Splenomegaly: none
* Bone marrow: normocellular with \< 30 lymphocytes, no B lymphoid nodules.

PR:

* Lymphadenopathy: decrease ≥ 50%
* Blood lymphocytes: decrease ≥ 50%
* Hepatomegaly: decrease ≥ 50%
* Splenomegaly: decrease ≥ 50%
* Bone marrow: not considered.

SD:

* Lymphadenopathy: change of ± 49%
* Blood lymphocytes: change of ± 49%
* Hepatomegaly: change of ± 49%
* Splenomegaly: change of ± 49%
* Bone marrow: not considered.

Overall survival (OS) represents the amount of time the participants remain alive after treatment. The outcome is reported as the number of participants remaining alive at 117 weeks (about 2 years and 3 months) after the start of treatment, a number without dispersion.

Progression-free survival (PFS) is a term that means to remain alive with progressive disease (PD). PD is defined as

* Lymphadenopathy: Increase ≥ 50%
* Blood lymphocytes: Increase ≥ 50%
* Hepatomegaly: Increase ≥ 50%
* Splenomegaly: Increase ≥ 50%
* Bone marrow: not considered.

The outcome is reported as the number of participants who remained alive without PD 117 weeks after the beginning of treatment.

Time-to-progression (TTP) is a measure of the length of time from the beginning of treatment until progressive disease (PD). PD is defined as

* Lymphadenopathy: Increase ≥ 50%
* Blood lymphocytes: Increase ≥ 50%
* Hepatomegaly: Increase ≥ 50%
* Splenomegaly: Increase ≥ 50%
* Bone marrow: not considered.

The outcome will be reported as the median TTP as determined by Kaplan-Meier methodology, with 95% confidence interval (95% CI).

Steven E. Coutre

Professor of Medicine

Patients receive ibrutinib PO QD beginning on week 1 day 1. Treatment with ibrutinib continues in the absence of disease progression or unacceptable toxicity. Patients also receive venetoclax PO QD beginning on week 9 day 1. Treatment with venetoclax continues up to week 61 day 7 in the absence of disease progression or unacceptable toxicity.

Ibrutinib: Administered at 420 mg/day, as oral capsules (3 x 140 mg), starting Day 1, Week 1.

Venetoclax: Administered as tablets, starting Day 1, Week 9, with dose increasing every 7 days through 5 dose levels (20 mg; 50 mg; 100 mg; 200 mg; 400 mg).

Treatment (Ibrutinib, Venetoclax)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Steven Edward Coutre, Professor of Medicine (Hematology)

Some participants withdrew consent before the assessment.

Complete Response (CR)

Duration of Response (DoR)

Minimal residual disease (MRD)-negative

Minimal residual disease (MRD)-positive

Test results were not available for all participants. "Negligible" was considered as negative.

Minimal Residual Disease (MRD)

Partial Response (PR)

Stable Disease (SD)

Some participants withdrew before the assessment.

Overall Response (OR)

Those participants who withdrew consent or were withdrawn for other medical treatments before 117 weeks are not included.

Overall Survival (OS)

Progression-free Survival (PFS)

An insufficient number of participants have experienced disease progression to determine a median value for that time period. This is expressed statistically as "Median Not Reached."

Time-to-progression (TTP)

An insufficient number of participants have advanced to a next treatment to determine a median value for that time period. This is expressed statistically as "Median Not Reached."

Spots Global Cancer Trial Database for Venetoclax and Ibrutinib in Patients With Relapsed/Refractory CLL or SLL

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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