Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Bendamustine Hydrochloride

Bortezomib

Antineoplastic Agents, Alkylating

Alkylating Agents

On days 1 and 4 of each cycle, bendamustine is given at 90 mg/m\^2 after bortezomib . Patients will be dose reduced to 75 mg/m\^2, and then to 60 mg/m\^2 bendamustine on days 1 and 4 if ANC is not \>1 x 10\^9/L and platelets are not \>50 x 10\^9/L on day 1 of each cycle.

Patients will be treated until disease progression after at least one cycle of treatment.

Bendamustine

On days 1 and 4 of each cycle, bortezomib is given first at 1.3 mg/m\^2 followed by bendamustine given at 90 mg/m\^2. Patients will be dose reduced to 75 mg/m\^2, and then to 60 mg/m\^2 bendamustine on days 1 and 4 if ANC is not \>1 x 10\^9/L and platelets are not \>50 x 10\^9/L on day 1 of each cycle.

Patients will be treated until disease progression after at least one cycle of treatment.

Amitabha Mazumder, MD

Patients with myeloma that has either not responded to previous treatment or has returned after previous treatment will be given a combination of the drugs bendamustine and bortezomib.

The bortezomib and bendamustine will be given using an intravenous line (IV) on days 1 and 4 of each cycle, with bortezomib being given first, before each dose of bendamustine. Each cycle will be 28 days long, so patients will be treated the first week of each cycle and then have 3 weeks 'off' (without any treatment). Disease assessments will be performed on day 22 of each cycle. Patients will receive the study drugs until their disease progresses or they are withdrawn from the study.

In other studies, bendamustine seems to work well with other drugs. Thus, this study hopes to show that the combination of bortezomib and bendamustine will have activity in relapsed/refractory myeloma.

Patients with relapsed and refractory myeloma who have a measurable paraprotein in the serum or urine or measurable protein by Freelite or measurable disease by plasmacytoma will be given a combination of bendamustine and bortezomib each cycle. Response rate (PR or better after 2 cycles) and duration of response will be assessed. Therapy will be continued until disease progression. The bendamustine would be used in a day 1, day 4 dosing schedule after each dose of bortezomib to take advantage of the chemosensitizing properties of bortezomib. This minimizes the days of treatment to just the first week and allows rebound of blood counts. This will be a phase II trial with dose reduction as necessary.

Bendamustine is a drug which appears to be non-cross-resistant with other alkylating agents in vitro and in vivo. Thus, we hypothesize that the combination of bortezomib and bendamustine will have activity in relapsed/refractory myeloma.

Bortezomib and Bendamustine to Treat Relapsed/Refractory Myeloma

Phase II Trial of Bortezomib and Bendamustine in the Treatment of Relapsed/Refractory Myeloma

These criteria included measures of alteration in the natural history of disease, hematologic improvement, cytogenetic response, and improvement in health-related quality of life.The IWG criteria define 4 aspects of responses based on treatment goals: (1) altering the natural history of the disease, (2) cytogenetic response, (3) hematologic improvement (HI), and (4)Quality of Life (QOL)

Study toxicity will be measured on an ongoing basis, no less then once per 28-day cycle.

Time from response to relapse. Response would have been assessed using European Group for Blood and Marrow Transplantation (EBMT) criteria modified to include near complete remission (nCR) and very good partial remission (VGPR

Cephalon

NYU Langone Health

Bendamustine: On days 1 and 4 of each cycle, bendamustine is given at 90 mg/m\^2 after bortezomib . Patients will be dose reduced to 75 mg/m\^2, and then to 60 mg/m\^2 bendamustine on days 1 and 4 if ANC is not \>1 x 10\^9/L and platelets are not \>50 x 10\^9/L on day 1 of each cycle.

Patients will be treated until disease progression after at least one cycle of treatment.

Bortezomib: On days 1 and 4 of each cycle, bortezomib is given first at 1.3 mg/m\^2 followed by bendamustine given at 90 mg/m\^2. Patients will be dose reduced to 75 mg/m\^2, and then to 60 mg/m\^2 bendamustine on days 1 and 4 if ANC is not \>1 x 10\^9/L and platelets are not \>50 x 10\^9/L on day 1 of each cycle.

Patients will be treated until disease progression after at least one cycle of treatment.

Bortezomib and Bendamustine

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Michael Grossbard, MD

Participant data was not analyzed because PI left institution

Percent Change Response Rate (Partial Response or Better After 2 Cycles) Following Treatment With Bortezomib and Bendamustine

Participant data was not analyzed because PI left institution. Data were not available for analysis.

Toxicity of This Regimen.

Duration of Response of This Regimen.

Overall Study

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Anti-Infective Agents

Fibrinolytic Agents

Anticoagulants

Antipyretics

Antirheumatic Agents

Analgesics

Platelet Aggregation Inhibitors

Bone Density Conservation Agents

Antibodies

Dexamethasone

Anti-Bacterial Agents

Heparin

Aspirin

Calcium

Lenalidomide

Dexamethasone acetate

Antibiotics, Antitubercular

Warfarin

Immunoglobulins

Omeprazole

Calcium heparin

Heparin, Low-Molecular-Weight

Tinzaparin

Dalteparin

Acyclovir

Calcium, Dietary

Immunoglobulins, Intravenous

Fluconazole

Trimethoprim, Sulfamethoxazole Drug Combination

Histamine H2 Antagonists

Proton Pump Inhibitors

Ranitidine

Ranitidine bismuth citrate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Treatment with Bendamustine in combination with Lenalidomide and Dexamethasone will be administered on an outpatient basis. Each treatment cycle will be 28 days dosed according to the Dose Escalation Schema.

Bendamustine is given intravenously (into a vein or IV infusion) on days 1 and 2 of each cycle. Each bendamustine infusion will take 60 minutes

Lenalidomide is taken orally (by mouth) in the morning on days 1 through 21 of each cycle.

Dexamethasone is taken orally (by mouth) on days 1, 8, 15, and 22 of each cycle.

All patients will receive enteric coated aspirin, 325 mg, QD while on study. If patient is unable to tolerate aspirin, patient should receive other types of anti-coagulation like Coumadin or low molecular weight heparin.

All patients will receive prophylaxis with either an H-2 blocker or proton pump inhibitor (PPI) while on study medications. Suggested medications included ranitidine 150 mg PC BID or omeprazole 20 mg PO QD or equivalent.

Prophylaxis

PCP antibiotic prophylaxis with a Bactrim will be recommended. In case of history of zoster or fungal infection a prophylaxis with Acyclovir or Diflucan should be also considered.

Antibiotic

Vital signs (heart rate, breathing rate, blood pressure, and temperature) will be measured, and Blood tests to check CBC, Calcium, Electrolytes, serum, creatinine, and BUN. This follow up will take place at the Hillman Cancer Center, or whichever cancer center in which the subject is treated.

Biweekly Follow Up

At the beginning of each treatment cycle subjects will undergo a Physical exam, a Performance status check, Recording of any new symptoms or side effects and any new medications, Blood tests (including blood chemistry, organ function and indicators of disease), Urine test, and pregnancy test (if applicable).

Cyclical Follow Up

Every other cycle subjects' disease will be restaged. This will be accomplished by their treatment physician. Re-staging procedures includes a regular office visit, x-ray, and a bone marrow biopsy. Subjects will spend approximately 4 hours at the Hillman Cancer Center or the UPMC Cancer Center location where they are being treated for this re-staging.

Restaging

After subjects stop receiving the study drugs, they will be followed every 3 months for the first two years, every 6 months for years 2-5, and annually thereafter. The following procedures, which are considered routine for their cancer care, will be done as part of this follow-up:

* Physical exam
* Performance status (check of ability to perform daily functions)
* Recording of any new symptoms and any new medications being taken
* Blood tests to check blood counts (numbers of red and white blood cells and platelets), blood chemistry (to check organ function), and indicators of disease (immunoglobulins)
* Urine test (24hr urine)
* Women who are able to have children will have a pregnancy test (4 weeks after their last dose of lenalidomide).
* A check of the status of disease (includes bone marrow biopsy, skeletal survey, and blood and urine tests). Bone marrow biopsy will be done at the end of treatment, if subjects have a complete response, and their disease gets worse.

Post-Treatment Follow Up

Robert L Redner, M.D.

The purpose of this study is to see if the combination of bendamustine, lenalidomide and dexamethasone will help people with multiple myeloma that has returned after standard treatment or has been resistant to other treatments.

Bendamustine in Combination With Lenalidomide and Dexamethasone in Refractory or Relapsed Multiple Myeloma

Phase I Study of Bendamustine in Combination With Lenalidomide (CC-5013) and Dexamethasone in Patients With Refractory or Relapsed Multiple Myeloma

Robert Redner, MD

Professor, Division of Hematology/Oncology, Department of Medicine

Cyclophosphamide

Chloroquine

Chloroquine diphosphate

Immunosuppressive Agents

Amebicides

Antiprotozoal Agents

Antiparasitic Agents

Antimalarials

VELCADE given by intravenous push at 1.3 mg/m\^2 on days 1, 4, 8, 11, 22, 25, 29 and 32.

Cyclophosphamide given at 50 mg orally twice per day on days 1-14 and 22-35.

Chloroquine given at 500 mg orally daily on days 1-14 and 22-35.

Each cycle is 42 days in length.

Velcade

This pilot phase II trial studies how well giving bortezomib and cyclophosphamide together with chloroquine works in treating patients with relapsed or refractory multiple myeloma.

Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chloroquine may help chemotherapy drugs work better by making cancer cells more sensitive to the drug. Giving bortezomib and cyclophosphamide together with chloroquine may kill more cancer cells.

Chloroquine in Combination With VELCADE and Cyclophosphamide for Relapsed and Refractory Multiple Myeloma

A Phase II, Trial of Chloroquine in Combination With VELCADE and Cyclophosphamide in Patients With Relapsed and Refractory Myeloma

Response rate is defined as the percentage of patients who have a complete response (CR) or partial response (PR). Responses were assessed every two cycles of treatment, based on the criteria published by the International Myeloma Working Group (Durie, et al, 2006). Per International Myeloma Working Group response criteria:

CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow PR: \> 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \< 200 mg/24 h

Adverse events reported here were at least possibly related to the protocol therapy.

Duration of response is the time from response (CR or PR) until progression of disease or relapse. Responses and progression were evaluated based on the criteria published by the International Myeloma Working Group (Durie, et al, 2006).

Millennium Pharmaceuticals, Inc.

All adverse events were reported regardless of attribution to protocol therapy.

Velcade+Cyclophosphamide+Chloroquine

45-53 years

54-63 years

64-73 years

74-83 years

Age, Customized

Race (NIH/OMB)

Response Rate (CR + PR After 2 Cycles)

Fatigue

Hemoglobin

Nasal cavity/paranasal reactions

ANC/AGC

Pain: pleural

Platelets

Number of Participants With Adverse Events of Grade 3 or Higher

Study was terminated prior to collection of this data point.

Percentage of Subjects Who Have Complete Response or Partial Response and Have 2+ or Higher Autophagy

Median Duration of Response of This Regimen

Bevacizumab

Myeloma Proteins

Paraproteins

Immunoglobulin M

Immunoglobulin A

Bortezomib will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented.

David S Siegel, MD, PhD

The purpose of this study is to determine whether the combination of bevacizumab and bortezomib have increased efficacy in the treatment of relapsed/ refractory multiple myeloma.

Rationale: With the identification of thalidomide as an active agent in Multiple Myeloma, the role of angiogenesis in its pathogenesis has become a subject of much investigation. Micro vessel density (neovascularization) is inversely related to prognosis in Multiple Myeloma. Response to thalidomide was felt to correlate with a decline in microvessel density (Singhal et al NEJM). While the mechanism of neovascularization is yet to be fully elucidated, a number of models have shown VEGF to play a central role.

Thalidomide has been shown to synergize with a number of agents used to treat MM, including bortezomib. (Wang et al ASH 2005) This would justify the use of other therapeutics with known antiangiogenic activity in conjunction with established antimyeloma therapies.

Bortezomib, which has the precedence of known synergy with Thalidomide and has an extremely well established optimal dose, schedule, response rate, event free survival, and overall survival would make it an excellent candidate for combination therapy with other established antiangiogenic compounds.

There have been several reports of the role of VEGF in multiple myeloma. It has been shown that multiple myeloma cells secreteVEGF, which further promotes production of IL-6 in BMSCs, as well as migration and proliferation of the tumor cells. Thus VEGF is both an autocrine growth factor and trigger of IL-6-mediated paracrine multiple myeloma cell growth. Recent reports have highlighted the major role of VEGF in multiple myeloma pathogenesis, demonstrating the VEGF also increases microvessel density in the bone marrow. VEGF also inhibits dendritic cells. Taken together, these preclinical reports make strong suggestion for the promise of VEGF targeted agents in multiple myeloma (Le Gouill et al 2004).

A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma

A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed Refractory Multiple Myeloma

Study Schema: Bortezomib will be administered on Days 1. 4, 8, and 11. Response will be assessed subsequent to each 21-day cycle. Progression is defined using the Bladé criteria, defined progression as an increase of \>25% in paraprotein or urinary light chain excretion (or marrow plasma cell percentage in the marrow

The secondary objective of this study is to assess the safely and tolerability of the combination treatment of bevacizumnab and bortezomnib. Adjustments in the dosing schedule of bortezomib would be made for patients with adequate response as per Blade criteria and continue until disease progression or 18 months

Genentech, Inc.

Hackensack Meridian Health

Overall Survival (OS) - Overall Survival is Calculated at the Time of the Screening Evaluation to Death From Any Cause.

Drug Combination

7 subjects were consented 6 proceeded with treatment, 4 completed study: one failed screening and one was dropped due to non-compliance with protocol, one withdrew consent

The study was terminated prior to enrollment completion and formal analysis of the primary objectives was never conducted.

Dr. David Siegel

Bortezomib and Bevacizumab

Median Number of Cycles to Tumor Progression (TTP)

Bortezomilb will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bortezomib and Bendamustine to Treat Relapsed/Refractory Myeloma	NCT01315873	Multiple Myelom...	Bendamustine Bortezomib	18 Years -	NYU Langone Health
Bendamustine in Combination With Lenalidomide and Dexamethasone in Refractory or Relapsed Multiple Myeloma	NCT01042704	Myeloma	Bendamustine Lenalidomide Dexamethasone Aspirin Prophylaxis Antibiotic Biweekly Follow... Cyclical Follow... Restaging Post-Treatment ...	18 Years -	University of Pittsburgh
Chloroquine in Combination With VELCADE and Cyclophosphamide for Relapsed and Refractory Multiple Myeloma	NCT01438177	Multiple Myelom...	Velcade Cyclophosphamid... Chloroquine	18 Years -	NYU Langone Health
A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma	NCT00464178	Multiple Myelom...	Bortezomib	18 Years -	Hackensack Meridian Health

Spots Global Cancer Trial Database for relapsed myeloma