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 Patients will receive the study drugs until their disease progresses or they are withdrawn from the study.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

Lenalidomide

Pomalidomide

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity

pomalidomide

Mohamed Zaki, MD, PhD

The purpose of this study is to evaluate the efficacy and safety of pomalidomide monotherapy in subjects with refractory or relapsed and refractory multiple myeloma who were enrolled in study CC-4047-MM-003 (NCT01311687) and discontinued treatment with high-dose dexamethasone due to disease progression.

Study to Evaluate the Safety and Efficacy of Pomalidomide Monotherapy in Subjects With Refractory or Relapsed Refractory Multiple Myeloma

Open-label, Multi-center, Single Arm Study For The Safety And Efficacy Of Pomalidomide Monotherapy For Subjects With Refractory Or Relapsed And Refractory Multiple Myeloma. A Companion Study For Clinical Trial CC-4047-MM003

Objective response defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on Investigator Assessment.

SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level \<100 mg/24 hours; PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to \<200 mg/24 hours. A ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.

Objective response defined as a best overall response of complete response (CR) or partial response (PR) based on the CR and requires all of the following:

* Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days.
* \<5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed.
* No increase in size or number of lytic bone lesions.
* Disappearance of soft tissue plasmacytomas.

PR requires all of the following:

* ≥50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days.
* Reduction in 24-hour urinary light chain extraction by ≥90% or to \<200 mg, maintained at least 42 days.
* For patients with non-secretory myeloma, ≥50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days.

An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE is any AE occurring at any dose that:

* Results in death;
* Is life-threatening;
* Requires or prolongs existing inpatient hospitalization;
* Results in persistent or significant disability/incapacity;
* Is a congenital anomaly/birth defect;
* Constitutes an important medical event.

The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0):

Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required);-Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death

Progression-free survival was calculated as the time from randomization to disease progression as determined by the Investigator based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier.

Progressive disease requires 1 of the following:

* Increase of ≥ 25% from nadir in:

  * Serum M-component (absolute increase ≥ 0.5 g/dl)
  * Urine M-component (absolute increase ≥ 200 mg/24 hours)
  * In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase \> 100 mg/dl)
  * Bone marrow plasma cell percentage (absolute % ≥ 10%)
* Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas.

Time to progression (TTP) was calculated as the time from randomization to the first documented progression confirmed by the investigator and based on the International Myeloma Working Group Uniform Response criteria (IMWG).

Progressive disease requires 1 of the following:

* Increase of ≥ 25% from nadir in:

  * Serum M-component (absolute increase ≥ 0.5 g/dl)
  * Urine M-component (absolute increase ≥ 200 mg/24 hours)
  * In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase \> 100 mg/dl)
  * Bone marrow plasma cell percentage (absolute % ≥ 10%)
* Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas.
* Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.

Duration of Response (calculated for responders only) is defined as the time from the initial documented response (partial response or better) to confirmed disease progression by the investigator based on IMWG criteria.

Overall survival was calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.

Time to Response was calculated as the time from enrollment to the initial response (PR or better) based on IMWG and assessed by the investigator.

Celgene

Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity

Age, Continuous

American Indian or Alaska Native

Asian

Black or African American

Native Hawaiian or Other Pacific Islanders

White

Other

Not Collected

Race

Hispanic or Latino

Not Hispanic or Latino

Ethnicity

Participants with Prior Anti-Myeloma (MM) Therapies

Stage I

Stage II

Stage III

Missing

Stages are:

Stage I: Hemoglobulin \> 10 g/dL; serum calcium normal on roentgenogram; normal bone structure or solitary bone plasmacytoma only; Low M-component production rates (IgG value \< 5 g/dL, IgA value \< 3 g/dL; Bence Jones protein \< 4 g/24h)

Stage II: Overall data as minimally abnormal for stage I, and no single value as abnormal as defined for stage III

Stage III: 1 or more of below:

Hemoglobin \< 8.5 g/dL; serum calcium \> 12 mg/dL; Advanced lytic bone lesions (scale 3); High-M-component production rates (IgG value \> 7 g/dL, IgA value \> 5 g/dL; Bence Jones protein \> 12 g/24h)

Durie-Salmon Multiple Myeloma Stage before Study Entry

Time From First Pathologic Diagnosis

The intent-to-treat (ITT) population was defined as all enrolled participants.

Anne McClain, Senior Manager, Clinical Trial Disclosure

Intent to Treat Population was defined as all enrolled participants.

Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria Based on Investigator Assessment

Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity

pomalidomide: Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity

Intent to treat population includes all participants enrolled.

Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria Based on Investigator Assessment

Any adverse event

Grade 3-4 adverse event

AE related to pomalidomide

Grade 3-4 AE related to pomalidomide

Grade 5 AE

≥1 Serious AE (SAE)

≥1 SAE related to pomalidomide

≥1 SAE leading to stopping pomalidomide

≥AE leading to discontinuation of pomalidomide

≥1 study drug related AE leading to stopping POM

≥1 AE leading to reduction of pomalidomide

≥1 study drug related AE leading to reducing POM

≥1 AE leading to interruption of pomalidomide

≥ 1 study drug related interruption of POM

Safety population includes all participants who received at least one dose of study drug.

Number of Participants With Adverse Events and Type of Adverse Events

Intent to Treat included all participants enrolled.

Kaplan Meier Estimates for Progression Free Survival (PFS) by Investigator Based on IMWG

Intent to Treat includes all participants enrolled

Kaplan-Meier Estimate for Time to Progression (TTP) Based on Investigator Assessment Using IMWG Criteria

Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity

pomalidomide: Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity

Includes those who had a partial response or better.

Kaplan-Meier Estimate Duration of Response Based on Investigator Assessment Using IMWG Criteria

Intent to Treat population included all participants enrolled into the study

Kaplan-Meier Estimate for Overall Survival

Includes those who had at least a partial response or better; Intent to Treat

Time to Response Based on IMWG and Assessed by the Investigator

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

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

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.

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
Study to Evaluate the Safety and Efficacy of Pomalidomide Monotherapy in Subjects With Refractory or Relapsed Refractory Multiple Myeloma	NCT01324947	Multiple Myelom...	pomalidomide	18 Years -	Celgene
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 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone Versus High-Dose Dexamethasone in Subjects With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study	NCT01311687	Multiple Myelom...	pomalidomide Dexamethasone	18 Years -	Celgene
Study to Determine the Maximum Tolerated Dose for the Combination of Pomalidomide, Bortezomib and Low-Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma	NCT01497093	Multiple Myelom...	Pomalidomide Bortezomib Dexamethasone	18 Years -	Celgene
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 refractory myeloma