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

NCT01042704 | Completed Phase 1 DMC

• 1 other identifier: 07-089
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 22

Brief Summary

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.

Conditions

Myeloma

Keywords

Relapsed Myeloma; Refractory Myeloma

Outcome Measures

Primary Outcomes (1)

• To establish the dose of each drug recommended for a future Phase II protocol with the combination

  1 year

Secondary Outcomes (2)

• To explore anti-tumor activity of the combination of Bendamustine plus Lenalidomide and dexamethasone

  2.5 years

• Toxicity, time to progression, overall survival.

  2.5 years

Study Arms (1)

Bendamustine, Lenalidomide and Dexamethasone

EXPERIMENTAL

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.

Drug: Bendamustine; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Aspirin; Drug: Prophylaxis; Drug: Antibiotic; Other: Biweekly Follow Up; Other: Cyclical Follow Up; Other: Restaging; Other: Post-Treatment Follow Up

Interventions

Bendamustine DRUG

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

Bendamustine, Lenalidomide and Dexamethasone

Lenalidomide DRUG

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

Bendamustine, Lenalidomide and Dexamethasone

Dexamethasone DRUG

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

Bendamustine, Lenalidomide and Dexamethasone

Aspirin DRUG

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.

Bendamustine, Lenalidomide and Dexamethasone

Prophylaxis DRUG

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.

Bendamustine, Lenalidomide and Dexamethasone

Antibiotic DRUG

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.

Bendamustine, Lenalidomide and Dexamethasone

Biweekly Follow Up OTHER

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.

Bendamustine, Lenalidomide and Dexamethasone

Cyclical Follow Up OTHER

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).

Bendamustine, Lenalidomide and Dexamethasone

Restaging OTHER

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.

Bendamustine, Lenalidomide and Dexamethasone

Post-Treatment Follow Up OTHER

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.

Bendamustine, Lenalidomide and Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed symptomatic Multiple Myeloma, Salmon-Durie Stage II or III or International Staging System II or III that has been previously treated with at least one cycle of a specific therapy; after which the patient has shown progressive or refractory disease, and must meet at least one of the following parameters of measurable disease:
• Bone marrow plasmacytosis with \> 10% plasma cells, or sheets of plasma cells, or biopsy proven plasmacytoma which must be obtained within 6 weeks prior to registration.
• Measurable levels of monoclonal protein (M protein): \> 1 g/dL of IgG or IgM M-protein or \> 0.5 g/dL IgA or IgD M protein on serum protein electrophoresis OR \> 200 mg of free light chain on a 24 hour urine protein electrophoresis which must be obtained within 4 weeks prior to registration OR \> 20 mg/dL involved free light chain on serum free light chain testing with an abnormal kappa:lambda light chain ratio. Note that if both serum and urine m-components are present, both must be followed in order to evaluate response. Both SPEP and UPEP must be performed within 28 days prior to registration.
• Patients with lytic bone disease, defined as at least one lytic lesion that can be accurately measured in at least one dimension.
• Patients must have received prior chemotherapy for their myeloma, but not in the last 4 weeks. Patients may have previously received autologous peripheral blood stem cell transplantation. Prior treatment with lenalidomide is allowed.
• Patients should not have received any radiation for the preceding 4 weeks before entry onto the study. Exception: local radiation therapy for symptomatic bone lesions (eg,uncontrolled pain or high risk of pathologic fracture)
• Age \>= 18 years
• Life expectancy of greater than 6 months.
• ECOG performance status \>=2 (Karnofsky \>=60%). Patients with PS of 3 are eligible if their PS is due to pain, which would likely improve with treatment.
• Patients must have normal organ and marrow function as defined below, obtained within 4 weeks prior to registration:
• Hgb \> 9 g/dL (which may be supported by transfusion or growth factors)
• leukocytes \>=2,000/ml
• absolute neutrophil count ≥1000/ ml
• platelets \>=75,000/mcL
• total bilirubin \>=2.5 mg/dl

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Exception: local radiation therapy for symptomatic bone lesions (eg, uncontrolled pain or high risk of pathologic fracture)
• Patients receiving any other investigational agents.
• Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide and/or Bendamustine or other agents used in the study.
• Patients with a second malignancy other than squamous/basal cell carcinoma of the skin or in situ carcinoma of the cervix unless the tumor was curatively treated at least two years previously.
• Inability to comply with study and/or follow-up procedures.
• If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment:
• Must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices).
• Must have a platelet count \>75,000.
• Must have stable INR between 2-3.
• Patients who have not collected hematopoietic progenitors and are potential candidates for autologous transplantation .
• Patients that have a serious cardiac condition, such as myocardial infarction within 6 months or heart disease as defined by the New York Heart Association Class III or IV,
• Patients with prior allogeneic stem cell transplant.
• Non-secretory patients (i.e., patients who do not meet the minimum M-protein or light chain criteria)

Sponsors & Collaborators

• Robert Redner, MD: lead
• Cephalon: collaborator

Study Sites (22)

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

UPMC Cancer Centers - Teramana Cancer Center

Steubenville, Ohio, 43952, United States

Location

UPMC Cancer Centers - Beaver

Beaver, Pennsylvania, 15009, United States

Location

UPMC Cancer Centers - Jefferson

Clairton, Pennsylvania, 15025, United States

Location

UPMC Cancer Centers - Arnold Palmer at Mountain View

Greensburg, Pennsylvania, 15601, United States

Location

UPMC Cancer Centers - Arnold Palmer at Oakbrook

Greensburg, Pennsylvania, 15601, United States

Location

UPMC Cancer Centers - Indiana

Indiana, Pennsylvania, 15701, United States

Location

UPMC Cancer Centers - Johnstown

Johnstown, Pennsylvania, 15901, United States

Location

Hematology-Oncology Associates of UPCI

McKeesport, Pennsylvania, 15132, United States

Location

Hematology/Oncology - Private Practice

McKeesport, Pennsylvania, 15132, United States

Location

UPMC Cancer Centers - Monroeville

Monroeville, Pennsylvania, 15146, United States

Location

UPMC Cancer Centers - Arnold Palmer at Mt. Pleasant

Mount Pleasant, Pennsylvania, 15666, United States

Location

UPMC Cancer Centers - New Castle

New Castle, Pennsylvania, 16105, United States

Location

UPMC Cancer Centers - St. Margaret's

Pittsburgh, Pennsylvania, 15215, United States

Location

UPMC Cancer Centers - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

UPMC Cancer Centers - Passavant

Pittsburgh, Pennsylvania, 15237, United States

Location

VA Healthcare System - 646

Pittsburgh, Pennsylvania, 15240, United States

Location

UPMC Cancer Centers - Drake

Pittsburgh, Pennsylvania, 15241, United States

Location

UPMC Cancer Centers - Uniontown

Uniontown, Pennsylvania, 15401, United States

Location

UPMC Cancer Centers - Washington

Washington, Pennsylvania, 15301, United States

Location

UPMC Cancer Centers - North Hills

Wexford, Pennsylvania, 15090, United States

Location

UPMC Cancer Centers - Windber

Windber, Pennsylvania, 15963, United States

Location

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MeSH Terms

Conditions

Neoplasms, Plasma Cell

Interventions

Bendamustine Hydrochloride; Lenalidomide; Dexamethasone; Aspirin; Anti-Bacterial Agents

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

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; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Robert L Redner, M.D.

  University of Pittsburgh Physicians, Hematology/Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Division of Hematology/Oncology, Department of Medicine

Study Record Dates

• First Submitted: January 4, 2010
• First Posted: January 5, 2010
• Study Start: February 1, 2008
• Primary Completion: January 1, 2011
• Study Completion: March 1, 2015
• Last Updated: July 31, 2017

Record last verified: 2017-07

Locations

US (22)