Brief Summary
The primary objective of this study is to evaluate the addition of idelalisib to bendamustine/rituximab on progression-free survival (PFS) in adults with previously treated indolent non-Hodgkin lymphoma (iNHL).
An increased rate of deaths and serious adverse events (SAEs) among participants with front-line chronic lymphocytic leukemia (CLL) and early-line iNHL treated with idelalisib in combination with standard therapies was observed by the independent data monitoring committee (DMC) during regular review of 3 Gilead Phase 3 studies. Gilead reviewed the unblinded data and terminated this study in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA).
An increased rate of deaths and serious adverse events (SAEs) among participants with front-line chronic lymphocytic leukemia (CLL) and early-line iNHL treated with idelalisib in combination with standard therapies was observed by the independent data monitoring committee (DMC) during regular review of 3 Gilead Phase 3 studies. Gilead reviewed the unblinded data and terminated this study in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA).
Brief Title
Efficacy and Safety of Idelalisib (GS-1101) in Combination With Bendamustine and Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas
Categories
Completion Date
Completion Date Type
Actual
Conditions
Indolent Non-Hodgkin's Lymphomas
Eligibility Criteria
Key Inclusion Criteria:
* Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following
1. Follicular lymphoma (FL) Grade 1, 2, or 3a
2. Small lymphocytic lymphoma (SLL)
3. Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)
4. Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)
Key Exclusion Criteria:
* History of lymphoid malignancy other than those allowed per inclusion criteria.
* Ongoing drug-induced liver injury, active hepatitis C, active hepatitis B, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
* Prior treatment with bendamustine that was not effective.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
* Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following
1. Follicular lymphoma (FL) Grade 1, 2, or 3a
2. Small lymphocytic lymphoma (SLL)
3. Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)
4. Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)
Key Exclusion Criteria:
* History of lymphoid malignancy other than those allowed per inclusion criteria.
* Ongoing drug-induced liver injury, active hepatitis C, active hepatitis B, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
* Prior treatment with bendamustine that was not effective.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:
* Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following
1. Follicular lymphoma (FL) Grade 1, 2, or 3a
2. Small lymphocytic lymphoma (SLL)
3. Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)
4. Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)
inclusion criteria.
* Ongoing drug-induced liver injury, active hepatitis C, active hepatitis B, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
* Prior treatment with bendamustine that was not effective.
Note: Other protocol defined Inclusion/
* Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following
1. Follicular lymphoma (FL) Grade 1, 2, or 3a
2. Small lymphocytic lymphoma (SLL)
3. Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)
4. Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)
inclusion criteria.
* Ongoing drug-induced liver injury, active hepatitis C, active hepatitis B, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
* Prior treatment with bendamustine that was not effective.
Note: Other protocol defined Inclusion/
Gender
All
Gender Based
false
Keywords
iNHL
indolent NHL
follicular lymphoma
CAL-101
rituximab
bendamustine
small lymphocytic lymphoma
lymphoplasmacytoid lymphoma
Waldenstrom macroglobulinemia
LPL
WM
Marginal zone lymphoma
MZL
SLL
FL
GS-1101
PI3K inhibitor
idelalisib
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01732926
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-313-0125
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Bendamustine and Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas
Primary Outcomes
Outcome Description
PFS is defined as the interval from randomization to the earlier of the first documentation of definitive indolent non-Hodgkin lymphomas (iNHL) disease progression or death from any cause. Definitive iNHL disease progression is progression based on standard criteria. PFS was to be assessed by an independent review committee (IRC).
Outcome Measure
Progression-free Survival (PFS)
Secondary Ids
Secondary Id
2012-004034-42
Secondary Outcomes
Outcome Description
Complete response rate is defined as the proportion of participants who achieve a complete response. CR rate was to be assessed by an IRC.
Outcome Measure
Complete Response Rate (CR)
Outcome Description
Overall response rate is defined as the proportion of participants who achieve a complete response or partial response (or very good partial response (VGPR) or minor response (MR) for participants with Waldenstrom's). ORR was to be assessed by an IRC.
Outcome Measure
Overall Response Rate (ORR)
Outcome Description
Lymph node response rate is defined as the proportion of participants who achieve ≥ 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters of index lesions. Lymph node response rate was to be assessed by an IRC.
Outcome Measure
Lymph Node Response Rate
Outcome Description
Overall survival is defined as the interval from randomization to death from any cause.
Outcome Measure
Overall Survival (OS)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ramakrishna Battini
Investigator Email
rabattin@montefiore.org
Investigator Phone
718-920-4826
Categories Mesh Debug
Blood & Bone Marrow Cancers --- LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL
Cancer --- NEOPLASMS
Blood & Bone Marrow Cancers --- LYMPHOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- LYMPHATIC DISEASES
Blood & Bone Marrow Cancers --- IMMUNOPROLIFERATIVE DISORDERS
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
Blood & Bone Marrow Cancers --- LEUKEMIA, LYMPHOID
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- NEOPLASMS, PLASMA CELL
Blood & Bone Marrow Cancers --- HEMOSTATIC DISORDERS
Blood & Bone Marrow Cancers --- VASCULAR DISEASES
Heart/Cardiovascular --- VASCULAR DISEASES
Blood Disorders --- CARDIOVASCULAR DISEASES
Blood & Bone Marrow Cancers --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- CARDIOVASCULAR DISEASES
Blood & Bone Marrow Cancers --- PARAPROTEINEMIAS
Blood & Bone Marrow Cancers --- BLOOD PROTEIN DISORDERS
Blood & Bone Marrow Cancers --- HEMORRHAGIC DISORDERS
MeSH Terms
LYMPHOMA, FOLLICULAR
LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL
WALDENSTROM MACROGLOBULINEMIA
LYMPHOMA, B-CELL, MARGINAL ZONE
LYMPHOMA, NON-HODGKIN
LYMPHOMA
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
HEMIC AND LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
IMMUNE SYSTEM DISEASES
LEUKEMIA, B-CELL
LEUKEMIA, LYMPHOID
LEUKEMIA
HEMATOLOGIC DISEASES
CHRONIC DISEASE
DISEASE ATTRIBUTES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
NEOPLASMS, PLASMA CELL
HEMOSTATIC DISORDERS
VASCULAR DISEASES
CARDIOVASCULAR DISEASES
PARAPROTEINEMIAS
BLOOD PROTEIN DISORDERS
HEMORRHAGIC DISORDERS
LYMPHOMA, B-CELL
IDELALISIB
RITUXIMAB
BENDAMUSTINE HYDROCHLORIDE
COUNTERFEIT DRUGS
ANTIBODIES, MONOCLONAL, MURINE-DERIVED
ANTIBODIES, MONOCLONAL
ANTIBODIES
IMMUNOGLOBULINS
IMMUNOPROTEINS
BLOOD PROTEINS
PROTEINS
AMINO ACIDS, PEPTIDES, AND PROTEINS
SERUM GLOBULINS
GLOBULINS
BUTYRATES
ACIDS, ACYCLIC
CARBOXYLIC ACIDS
ORGANIC CHEMICALS
NITROGEN MUSTARD COMPOUNDS
MUSTARD COMPOUNDS
HYDROCARBONS, HALOGENATED
HYDROCARBONS
BENZIMIDAZOLES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS