Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Infections

Symptoms and General Pathology

Rare Diseases

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Burkitt Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Communicable Diseases

Epstein-Barr Virus Infections

Virus Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Anti-Inflammatory Agents

Amino Acids

Antibodies

Antibodies, Monoclonal

Venetoclax

Obinutuzumab

Prednisone

Lenalidomide

Immunoglobulins

Ibrutinib

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Tyrosine

iPOR (ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycle 1; followed by ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 2-6

ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 1-6

Administered orally, days 2-14, at varying doses of 200-800 mg (based upon assigned dose level); every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity

Administered orally, days 1-14, at a dose of 560 mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity

Administered orally, days 1-7, at a dose of 100 mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity

Administered intravenously, days 1 and 2, at a dose of 1000 mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity

Administered orally, days 1-15, at a dose of 15 mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity

Revlimid (lenalidomide)

NCIMO Referral Office

Christopher J Melani, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Background:

B-cell lymphoma is a cancer of white blood cells found in the lymph nodes. It affects the system that fights infections and disease. Researchers want to learn how certain drugs work together to treat B-cell lymphomas. The drugs are venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR).

Objective:

To study the safety of ViPOR for people with B-cell lymphoma.

Eligibility:

People ages 18 and older with B-cell lymphoma whose cancer has returned or not improved after treatment

Design:

Participants will be screened with:

* Medical history
* Physical exam
* Blood, urine, and heart tests
* Tissue sample from previous procedure
* Imaging scans
* Registration for counseling on the risks of lenalidomide. They must get counseling at least every 28 days.

Participants will have a bone marrow aspiration before treatment.

Participants may have tumor samples taken.

Participants will get ViPOR in 21-day cycles. For up to 6 cycles:

* Participants will get one drug by IV on days 1 and 2.
* Participants will take the other four drugs by mouth on most days. After their first dose of venetoclax, they will stay in the clinic for at least 8 hours and return the next day for monitoring. They may be admitted for more drugs or monitoring.

Participants will keep a drug diary.

Participants will have a physical exam and blood and urine tests at least once per cycle. They will have scans 4 times over 6 cycles.

Participants will have a visit about 1 month after their last dose of study drug. They will then have visits every few months for 3 years, and once a year for years 4 and 5. Visits include a physical exam, blood tests, and scans.

Background:

Combination chemotherapy with Rituximab has been the mainstay of treatment for CD20-positive B-cell lymphomas

Significant advances have been made in curing aggressive B-cell lymphomas with chemoimmunotherapy but indolent lymphomas and relapsed/refractory aggressive lymphomas remain mostly incurable with chemotherapy alone

Targeted therapies aimed at disrupting key survival pathways in lymphoid malignancies are emerging and showing significant activity in NHL in both the relapsed and first-line settings

Mechanistically-based combinations of targeted agents are likely to benefit patients who cannot tolerate or who relapse after or are refractory to standard chemoimmunotherapy

ViPOR targets major survival pathways in B-cell lymphomas including BCL-2 (apoptosis); BTK (B-cell receptor signaling and NFKB); Cereblon (NFKB) and CD20.

Objectives:

Phase 1b: To determine the maximum tolerated dose (MTD) and the safety and toxicity profile of the combination of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab and Revlimid(R) (ViPOR) in relapsed/refractory B-cell malignancies

Phase 2: To determine the overall response rate (ORR) and complete response (CR) rate of ViPOR in relapsed/refractory B-cell malignancies

Eligibility:

Women and men greater than or equal 18 years of age

ECOG performance status of less than or equal to 2

Histologically or cytologically confirmed relapsed and/or refractory B-cell lymphoma, excluding CLL/SLL. NOTE: untreated and relapsed and/or refractory MCL are included in the phase 2 MCL expansion.

Adequate organ function unless dysfunction secondary to lymphoma effect

Design:

Open-label, single-center, non-randomized phase 1b/2 study

Phase 1b: Standard 3 + 3 design will be used to determine the MTD of dose-escalated venetoclax with fixed dose ibrutinib, prednisone, obinutuzumab and Revlimid(R) (ViPOR) in relapsed/refractory B-cell malignancies

Phase 2: Expansion cohorts of aggressive and indolent non-MCL patients and MCL patients will be treated at the MTD to determine the ORR and CR rate in these subtypes.

Maximum 6 cycles of combination targeted therapy every 21 days

To explore all dose levels in both non-MCL and MCL patient cohorts in the phase 1b study, and to assess the ORR and CR rate in aggressive and indolent non-MCL and MCL patient cohorts in a phase 2 dose expansion at the MTD, the accrual ceiling will be set at 145 patients.

Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma

Phase 1b/2 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma

.All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP. @@@@@@All collected IPD will be shared with collaborators under the terms of collaborative agreements.

Time from the date of study enrollment until the time of disease relapse, disease progression, or death, whichever occurs first, assessed every 3-6 months

Time from the date of from initial diagnosis until death from any cause; assessed every 3-6 months

Time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented or death, assessed every 3-6 months

National Cancer Institute (NCI)

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lenalidomide-treatment starts between 100 and 180 days after allogeneic stem cell transplantation. Three dose-levels will be investigated.

* Dose-level -1: 2.5 mg/d if 2.5mg capsules are available, day 1-21, otherwise 5 mg every other day, day 1-21
* Dose-level 0: 5 mg/d, day 1-21
* Dose-level 1: 10 mg/d, day 1-21
* Dose-level 2: 15 mg/d, day 1-21

3 pat. will be enrolled on dose level 0. If no DLTs are observed during cycles 1+2 dose will be escalated to the next higher level in the 3 patients. If 1 of 3 pat. experiences DLT at the current dose, then up to 3 more pat. will be accrued at the same level. If none of these 3 additional pat. experience DLT dose will be escalated in subsequent patients. If 1 of these 3 patients experiences DLT, the next lower level will be declared to be MTD and the study will be filled up with patients at this dose level up to 25 pat. overall.

If 2 or more of 3 pat. or 3 or more of 6 pat. in the same cohort encounter DLT, the MTD has been exceeded and the previous lower dose level will be declared as MTD and the study will be filled up with patients at this level up to 25 pat. overall.

If DLT is observed in level 0, the next dose level will be -1 for the following cohort of 3 patients. If level 2 is well tolerated without DLT, this level will be claimed as recommended dose for further trials.

Revlimid (Lenalidomide)

Nicolaus Kroeger, Prof. Dr.

This study is a Phase I (non-randomized) study evaluating three dose-levels of Lenalidomide in patients after allogeneic stem cell transplantation, accomplished in two institutions (University Medical Center Hamburg-Eppendorf/ University Medical Center Heidelberg).

Dose-finding of Lenalidomide as Maintenance in Multiple Myeloma

Dose-finding Study of Lenalidomide as Maintenance Therapy in Multiple Myeloma After Allogeneic Stem Cell Transplantation

Universitätsklinikum Hamburg-Eppendorf

Single Cohort of Multiple Myeloma Patients Treated with Revlimid

Revlimid (lenalidomide) as prescribed in usual clinical practice

Yu (Flora) Yao, MD

The primary objective of this study is to document efficacy and safety data in a real-world setting of Chinese multiple myeloma patients who have received at least one prior therapy treated with REVLIMID (lenalidomide).

This registry is prospective, multi-center, observational study and will collect efficacy and safety data on multiple myeloma adult patients who have received at least one prior therapy and take REVLIMID as part of standard care associated with patients' treatment in order to characterize the use, efficacy and outcomes of REVLIMID treatment.

The registry will capture data from 600 patients being prescribed REVLIMID in specified hospitals and all patients will be followed in the registry for two years after enrollment of the last patient.

Observational Registry Study of Chinese Patients Treated With Revlimid (Lenalidomide)

A Non-interventional, Observational Post-marketing Registry of Multiple Myeloma Adult Patients Treated With Revlimid (Lenalidomide) in China

Assessment of PFS using IMWG Uniform Response Criteria

Assessment of Response Rates (CR, VGPR, PR) using IMWG Uniform Response Criteria

Reason for dose interruption/reduction of REVLIMID, if this occurs. Reason for discontinuation of REVLMID

All Adverse Events (AEs) and occurrence of second primary malignancies (SPM)

Celgene

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Dexamethasone

Cyclophosphamide

Bortezomib

Dexamethasone acetate

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

VELCADE (bortezomib), dexamethasone, and Revlimid (lenalidomide)

VELCADE (bortezomib), dexamethasone, cyclophosphamide, Revlimid (lenalidomide)

VELCADE (bortezomib), dexamethasone, cyclophosphamide

Modified dosing of VELCADE (bortezomib), dexamethasone, cyclophosphamide

bortezomib 1.3 mg/m\^2 given via IV on days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on days 1, 8, 15 and 22 of a 6-week cycle for 4 cycles (maintenance).

VELCADE (bortezomib)

dexamethasone 40 mg orally on days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop

dexamethasone

cyclophosphamide 500 mg/m\^2 orally on days 1 and 8 of a 3-week cycle for 8 cycles, then stop

cyclophosphamide

lenalidomide 25 mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop (VDR arm)

lenalidomide 15 mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop (VDCR arm)

Medical Monitor

The purpose of this Phase 1/2 study is to evaluate the efficacy and safety of treatment with VELCADE, dexamethasone, and Revlimid® (VDR) as well as VELCADE, dexamethasone, cyclophosphamide, and Revlimid (VDCR) in patients with multiple myeloma who have received no prior treatment. This study will evaluate whether the addition of Revlimid to VELCADE and Dexamethasone will increase the complete response (CR)/ very good partial response (VGPR) rate.

Phase 1/2 Study of VELCADE® in Combination With Other Drugs to Treat Previously Untreated Multiple Myeloma Patients

Phase 1/2 Study of VELCADE® (Bortezomib), Dexamethasone, and Revlimid® (Lenalidomide) Versus VELCADE, Dexamethasone, Cyclophosphamide, and Revlimid Versus VELCADE, Dexamethasone and Cyclophosphamide in Subjects With Previously Untreated Multiple Myeloma

Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow.

Very good partial response requires serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 h

Evaluate the safety and tolerability of the combination therapy

Overall Response includes complete response and partial response.

Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow.

Partial response requires at least 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by at least 90% or to \< 200 mg per 24 hour.

Stringent Complete Response is defined as complete response plus normal free light chain (kappa/lambda) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.

Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow.

Near Complete response requires positive immunofixation on the serum and/or urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow.

Duration of response is the time from date of first documented confirmed response to date of first documented progressive disease. A confirmed response is a response that has been observed on at least two consecutive assessments.

Disease progression requires any one or more of the following: serum m-protein increase \>= 25% from nadir(absolute increase \>= 0.5 g/dL); Urine m-protein increase \>= 25% from nadir(absolute increase \>= 200 mg/24 hr), bone marrow plasma cell percentage increase \>= 25% from nadir(absolute increase \>= 10%), new bone lesion or soft tissue plasmacytomas.

Time to disease progression is defined as time from the date of randomization to the date of first documented progressive disease.

Disease progression requires any one or more of the following: serum m-protein increase \>= 25% from nadir(absolute increase \>= 0.5 g/dL); Urine m-protein increase \>= 25% from nadir(absolute increase \>= 200 mg/24 hr), bone marrow plasma cell percentage increase \>= 25% from nadir(absolute increase \>= 10%), new bone lesion or soft tissue plasmacytomas.

Time to response is defined as time from date of randomization to the date of the first documentation of a confirmed response. confirmed response is a response that has been observed on at least two consecutive assessments.

Progression-free survival is defined as time from the date of randomization to the date of the first documented progressive disease or death.

Disease progression requires any one or more of the following: serum m-protein increase \>= 25% from nadir(absolute increase \>= 0.5 g/dL); Urine m-protein increase \>= 25% from nadir(absolute increase \>= 200 mg/24 hr), bone marrow plasma cell percentage increase \>= 25% from nadir(absolute increase \>= 10%), new bone lesion or soft tissue plasmacytomas.

Overall survival is defined as time from the date of randomization to the date of death

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Millennium Pharmaceuticals, Inc.

From first dose of any study drug to end of treatment period

VELCADE (bortezomib), dexamethasone, and Revlimid (lenalidomide) Bortezomib: 1.3 mg/m\^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg orally \[PO\] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.

V-DR

VELCADE (bortezomib), dexamethasone, cyclophosphamide, Revlimid (lenalidomide) Bortezomib: 1.3 mg/m\^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Cyclophosphamide: 100 - 500 mg/m\^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.

Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.

VDCR

VELCADE (bortezomib), dexamethasone, cyclophosphamide Bortezomib: 1.3 mg/m\^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Cyclophosphamide: 500 mg/m\^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.

V-DC

Modified dosing of VELCADE (bortezomib), dexamethasone, cyclophosphamide Bortezomib: 1.3 mg/m\^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Cyclophosphamide: 500 mg/m\^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

VDC-mod

Total

Age, Categorical

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Dixie-Lee Esseltine, MD

Bortezomib: 1.3 mg/m\^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg orally \[PO\] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.

Bortezomib: 1.3 mg/m\^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Cyclophosphamide: 500 mg/m\^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.

Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.

Bortezomib: 1.3 mg/m\^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Cyclophosphamide: 500 mg/m\^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.

Bortezomib: 1.3 mg/m\^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Cyclophosphamide: 500 mg/m\^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

The response-evaluable population is defined as phase 2 patients with measurable disease at baseline and with at least 1 post baseline response assessment.

Number of Patients With Combined Complete Response and Very Good Partial Response

The safety population includes patients received any dose of any study drug.

Number of Patients With Adverse Events (AEs)

Number of Patients With Overall Response

Number of Patients With Stringent Complete Response Rate

Number of Patients With Complete Response Rate + Near Complete Response Rate

Responders (patients achieved complete and partial response) in the response evaluable population.

Duration of Response

The modified intent-to-treat population is defined as phase 2 patients received at least one dose of any drug.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma	NCT03223610	Lymphoma Non-Hodgkin Lym... Diffuse Large B... Burkitt Lymphom...	Venetoclax Ibrutinib Prednisone Obinutuzumab Revlimid (lenal...	18 Years -	National Institutes of Health Clinical Center (CC)
Dose-finding of Lenalidomide as Maintenance in Multiple Myeloma	NCT00778752	Multiple Myelom...	Revlimid (Lenal...	18 Years -	Universitätsklinikum Hamburg-Eppendorf
Observational Registry Study of Chinese Patients Treated With Revlimid (Lenalidomide)	NCT01947309	Multiple Myelom...	Revlimid (lenal...	18 Years -	Celgene
Phase 1/2 Study of VELCADE® in Combination With Other Drugs to Treat Previously Untreated Multiple Myeloma Patients	NCT00507442	Multiple Myelom...	VELCADE (bortez... dexamethasone cyclophosphamid... Revlimid (lenal...	18 Years -	Millennium Pharmaceuticals, Inc.

Spots Global Cancer Trial Database for revlimid (lenalidomide)