Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Heart and Blood Diseases

Rare Diseases

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Waldenstrom Macroglobulinemia

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Chronic Lymphocytic Leukemia

Follicular Lymphoma

Marginal Zone Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Bendamustine Hydrochloride

Rituximab

Idelalisib

Antineoplastic Agents, Immunological

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Participants will receive rituximab + bendamustine + idelalisib.

Participants will receive rituximab + bendamustine + placebo.

150 mg tablet administered orally twice daily

375 mg/m\^2 single-use vials administered intravenously every 4 weeks (up to a total of 6 infusions)

90 mg/m\^2 single-use vials administered intravenously for two consecutive days every 4 weeks (up to a total of 4-6 cycles as tolerated)

Bendamustine

Placebo

Gilead Study Director

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).

Efficacy and Safety of Idelalisib (GS-1101) in Combination With Bendamustine and Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas

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

Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.

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).

Complete response rate is defined as the proportion of participants who achieve a complete response. CR rate was to be assessed by an IRC.

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.

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.

Overall survival is defined as the interval from randomization to death from any cause.

Gilead Sciences

Safety Analysis Set: all participants who took at least 1 dose of study drug

Idelalisib 150 mg tablet twice daily + bendamustine intravenously (starting dose of 90 mg/m\^2 for up to 12 infusions) + rituximab intravenously (375 mg/m\^2 on Day 1 for a total of 6 infusions)

Idelalisib + Bendamustine + Rituximab

Placebo tablet twice daily + bendamustine intravenously (starting dose of 90 mg/m\^2 for up to 12 infusions) + rituximab intravenously (375 mg/m\^2 on Day 1 for a total of 6 infusions)

Placebo + Bendamustine + Rituximab

Total

Age, Continuous

Sex: Female, Male

Asian

Black or African American

White

Other

Not Permitted

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Russian Federation

United States

United Kingdom

Spain

Canada

Czech Republic

Sweden

Taiwan

Poland

Korea, Republic of

Italy

Israel

France

Australia

Germany

Region of Enrollment

The Intent to Treat (ITT) Analysis Set: all participants who were randomized regardless of whether they received any study treatment

Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.

Clinical Trial Disclosures

Progression-free Survival (PFS)

Complete Response Rate (CR)

Overall Response Rate (ORR)

Lymph Node Response Rate

Due to the early termination of the study, efficacy data were not mature for all participants, and therefore the prespecified analyses were not conducted.

Overall Survival (OS)

Idelalisib (Zydelig®) 150 mg tablet twice daily + bendamustine intravenously (starting dose of 90 mg/m\^2 for up to 12 infusions)

+ rituximab intravenously (375 mg/m\^2 on Day 1 for a total of 6 infusions)

Overall Study

Participants will receive rituximab + idelalisib.

Participants will receive rituximab + placebo. Following confirmation of iNHL disease progression by the independent review committee and unblinding, participants may be eligible to receive open-label idelalisib 150 mg twice daily.

375 mg/m\^2 administered intravenously weekly for 4 weeks, then every 8 weeks (up to a total of 8 infusions)

150 mg tablets administered orally twice daily

The primary objective of this study is to evaluate the effect of the addition of idelalisib to 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).

Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas

Progression-free survival (PFS) is defined as the interval from randomization to the earlier of the first documentation of definitive indolent non-Hodgkin lymphoma (iNHL) disease progression or death from any cause. PFS was to be assessed by an independent review committee (IRC).

Overall Response Rate (ORR) is defined as the proportion of participants who achieve a complete response or partial response (or very good partial response or minor response for participants with Waldenstrom's). ORR was to be assessed by an IRC.

Complete response rate is defined as the proportion of participants who achieve a complete response. Complete response rate was to be assessed by an IRC.

Idelalisib 150 mg tablet orally twice daily + rituximab 375 mg/m\^2 intravenously starting on Day 1 for a total of 8 infusions

Idelalisib + Rituximab

Placebo tablet orally twice daily + rituximab 375 mg/m\^2 intravenously starting on Day 1 for a total of 8 infusions

Placebo + Rituximab

Unknown or Not Reported

Singapore

Romania

Hungary

Japan

Portugal

Intent-to-Treat (ITT) Analysis Set: all participants who were randomized regardless of whether they received any study treatment

Progression Free Survival

Overall Response Rate

Complete Response Rate

Overall Survival

Idelalisib (Zydelig®) 150 mg tablet orally twice daily + rituximab 375 mg/m\^2 intravenously starting on Day 1 for a total of 8 infusions

Infections

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma, T-Cell

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Lymphoma, Mantle-Cell

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Burkitt Lymphoma

Leukemia, B-Cell

Hematologic Diseases

Chronic Disease

Disease Attributes

Communicable Diseases

Epstein-Barr Virus Infections

Virus Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Acute Non Lymphoblastic Leukemia

Mantle Cell Lymphoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Acute Graft Versus Host Disease

Richter Syndrome

Participants will be administered escalating doses of zilovertamab vedotin at 0.50, 1.00, 1.50, 2.25, 2.50, 2.75, and 3.00 mg/kg IV on Day 1 of repeated 21-day cycles (Q1/3W).

Participants will be administered escalating doses of zilovertamab vedotin at 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, and 2.25 mg/kg IV on Day 1 and 8 of repeated 21-day cycles (Q2/3W).

Participants will be administered escalating doses of zilovertamab vedotin at 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, and 2.25 mg/kg IV on Day 1, 8, and 15 of repeated 21-day cycles (Q3/4W).

Zilovertamab vedotin administered via IV infusion per Schedule 1, 2, or 3 according to participant allocation.

Zilovertamab vedotin

Medical Director

The purpose of this study is to evaluate the safety, pharmacokinetics, immunogenicity, and efficacy of zilovertamab vedotin given intravenously (IV) across a range of dose levels in participants with previously treated hematological cancers including acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), Burkitt lymphoma (BL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), Richter transformation lymphoma (RTL), and T-cell non-Hodgkin lymphoma (NHL).

Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels within each dose schedule of zilovertamab vedotin using a 3+3 dose-escalation design.

A Study of Zilovertamab Vedotin (MK-2140) (VLS-101) in Participants With Hematologic Malignancies (MK-2140-001)

A Phase 1 Dose-Escalation and Cohort-Expansion Study of VLS-101 in Subjects With Hematological Malignancies (waveLINE-001)

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Participants will receive zilovertamab vedotin according to Schedule 1, 2, or 3. The MTD will be determined by the number of participants who experience a dose limiting toxicity (DLT). The MTD will be defined as the highest tested dose level at which ≥6 participants have been treated and which is associated with a Cycle 1 DLT in ≤17% of the participants.

Selection of the RDR will be based on consideration of short- and long-term safety information together with available pharmacokinetic, pharmacodynamic, and efficacy data. The RDR may be the MTD or may be a lower dose within the tolerable dose range.

Zilovertamab vedotin drug administration will be assessed by prescribing records and the average number of zilovertamab vedotin infusions administered will be determined.

An AE is any untoward medical occurrence in a participant administered a medicinal product; the event does not necessarily have a causal relationship with study drug administration or usage. Laboratory abnormalities, vital sign/oxygen saturation abnormalities, and adverse electrocardiogram (ECG) findings will also be recorded as AEs. A TEAE is defined as an AE that occurs or worsens in the period from the first dose of study drug administration to 30 days after the final dose of study drug administration. The number of participants with a TEAE will be reported for each arm.

A DLT is defined as a protocol pre-specified TEAE that occurs in Cycle 1 of zilovertamab vedotin therapy and is considered drug-related. Failure to recover to baseline by ≥21 days from the last dose of study drug in the current cycle due to a drug-related TEAE is also considered a DLT. The number of participants with a DLT will be reported for each arm.

An SAE is defined as an untoward medical occurrence that results in any of the following outcomes: death, life-threatening situation, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or other medically significant event.

Prespecified AESIs for this study will include: Grade ≥3 infusion reactions, tumor lysis syndrome (TLS) of any grade, and Grade ≥3 peripheral neuropathy. The number of participants with an AESI will be reported for each arm.

An AE is any untoward medical occurrence in a participant administered a medicinal product; the event does not necessarily have a causal relationship with study drug administration or usage. The number of participants that discontinue study treatment due to an AE will be reported for each arm.

The number of participants that use supportive care or concomitant medications will be reported for each arm.

Plasma concentration of zilovertamab vedotin will be reported for each arm.

Plasma concentration of total UC-961 antibody will be reported for each arm.

Plasma concentration of MMAE will be reported for each arm.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Cmax of zilovertamab vedotin.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Tmax of zilovertamab vedotin.

Blood samples collected predose and at multiple timepoints postdose will be used to determine AUC of zilovertamab vedotin.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Vd of zilovertamab vedotin.

Blood samples collected predose and at multiple timepoints postdose will be used to determine CL of zilovertamab vedotin.

Blood samples collected predose and at multiple timepoints postdose will be used to determine t1/2 of plasma concentration of zilovertamab vedotin.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Cmax of total UC-961 antibody.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Tmax of total UC-961 antibody.

Blood samples collected predose and at multiple timepoints postdose will be used to determine AUC of total UC-961 antibody.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Vd of total UC-961 antibody.

Blood samples collected predose and at multiple timepoints postdose will be used to determine CL of total UC-961 antibody.

Blood samples collected predose and at multiple timepoints postdose will be used to determine t1/2 of plasma concentration of total UC-961 antibody.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Cmax of MMAE.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Tmax of MMAE.

Blood samples collected predose and at multiple timepoints postdose will be used to determine AUC of MMAE.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Vd of MMAE.

Blood samples collected predose and at multiple timepoints postdose will be used to determine CL of MMAE.

Blood samples collected predose and at multiple timepoints postdose will be used to determine t1/2 of plasma concentration of MMAE.

Number of participants with zilovertamab vedotin-reactive antibodies will be assessed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety of Idelalisib (GS-1101) in Combination With Bendamustine and Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas	NCT01732926	Indolent Non-Ho...	Idelalisib Rituximab Bendamustine Placebo	18 Years -	Gilead Sciences
Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas	NCT01732913	Indolent Non-Ho...	Placebo Rituximab Idelalisib	18 Years -	Gilead Sciences
A Study of Zilovertamab Vedotin (MK-2140) (VLS-101) in Participants With Hematologic Malignancies (MK-2140-001)	NCT03833180	Chronic Lymphoc... Mantle Cell Lym... Follicular Lymp... Marginal Zone L... Diffuse Large B... Richter Transfo... Burkitt Lymphom... Lymphoplasmacyt... T-cell Non-Hodg... Acute Lymphoid ... Acute Myeloid L... Waldenstrom Mac...	Zilovertamab ve...	18 Years -	VelosBio Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
A Study of Zilovertamab Vedotin (MK-2140) (VLS-101) in Participants With Hematologic Malignancies (MK-2140-001)	NCT03833180	Chronic Lymphoc... Mantle Cell Lym... Follicular Lymp... Marginal Zone L... Diffuse Large B... Richter Transfo... Burkitt Lymphom... Lymphoplasmacyt... T-cell Non-Hodg... Acute Lymphoid ... Acute Myeloid L... Waldenstrom Mac...	Zilovertamab ve...	18 Years -	VelosBio Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Spots Global Cancer Trial Database for lymphoplasmacytoid lymphoma