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

Condition(s) targeted: Myeloma

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

Phase: Phase 1

Status: Recruiting

Sponsored by: University of Pittsburgh

Official(s) and/or principal investigator(s):
Suzanne Lentzsch, M.D., PhD, Principal Investigator, Affiliation: University of Pittsburgh Physicians, Hematology/Oncology

Overall contact:
Suzanne Lentzsch, M.D., PhD, Phone: 412-648-6586, Email: lentzschs@upmc.edu

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.

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

Study design: Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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

Secondary outcome:

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

Toxicity, time to progression, overall survival.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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

- AST(SGOT)/ALT(SGPT) >=5 X institutional upper limit of normal

- creatinine <2. 5 mg/dl

- Patients must not be pregnant or breast feeding. Due to the potential teratogenic

properties of lenalidomide, the use of this drug in patients that are pregnant is absolutely contraindicated. Further, all women of childbearing potential and sexually active males must agree to avoid conception while participating in this study. Specifically, women of childbearing potential must either agree to refrain from sexual intercourse or employ a dual method of contraception, one of which is highly effective (IUD, birth control pills, tubal ligation or partners vasectomy), and another additional method (condom, diaphragm, or cervical cap) for 4 weeks prior to receiving lenalidomide, and for four weeks after discontinuing this therapy. Sexually active males cannot participate unless they agree to use a condom (even if they have undergone a prior vasectomy) while having intercourse with a woman of child bearing potential while taking lenalidomide and for four weeks after stopping treatment. Women of child bearing potential (those who have not had a hysterectomy or the absence of menstrual periods for at least 24 consecutive months) must have a negative pregnancy test 10-14 days prior to the initiation of therapy and a repeat negative pregnancy test 24 hours prior to the initiation of lenalidomide.

- Ability to understand and the willingness to sign a written informed consent

document. Patient must be informed of the investigational nature of this study.

Exclusion Criteria:

- 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)

Suzanne Lentzsch, M.D., PhD, Phone: 412-648-6586, Email: lentzschs@upmc.edu

Karmanos Cancer Institute, Detroit, Michigan 48201, United States; Recruiting
Jeffrey Zonder, M.D., Phone: 313-576-8732, Email: zonderj@karmanos.org
Jeffery A Zonder, MD, Principal Investigator

UPMC Cancer Centers - Teramana Cancer Center, Steubenville, Ohio 43952, United States; Recruiting
Patrick L Kane, MD, Phone: 740-266-3900
Patrick L Kane, MD, Sub-Investigator
Mohammad P Rahman, MD, Sub-Investigator
Roy E Smith, MD, Sub-Investigator

UPMC Cancer Centers - Beaver, Beaver, Pennsylvania 15009, United States; Recruiting
William Ferri, Phone: 724-774-0778
William Ferri, MD, Sub-Investigator
Grace R Tarabay, MD, Sub-Investigator

UPMC Cancer Centers - Jefferson, Clairton, Pennsylvania 15025, United States; Recruiting
Martin Earl, MD, Phone: 412-469-5500
Martin Earle, MD, Sub-Investigator
Gauri Kiefer, MD, Sub-Investigator
Andrew Laman, MD, Sub-Investigator

UPMC Cancer Centers - Arnold Palmer at Oakbrook, Greensburg, Pennsylvania 15601, United States; Recruiting
Hyoung Kim, MD, Phone: 724-834-1463
Hyoung Kim, MD, Sub-Investigator
John Waas, MD, Sub-Investigator

UPMC Cancer Centers - Arnold Palmer at Mountain View, Greensburg, Pennsylvania 15601, United States; Recruiting
Terry Evans, MD, Phone: 724-838-1900
Terry Evans, MD, Sub-Investigator
Franklin Viverette, MD, Sub-Investigator
Matthew Sulecki, MD, Sub-Investigator
Jin Lee, MD, Sub-Investigator

UPMC Cancer Centers - Indiana, Indiana, Pennsylvania 15701, United States; Recruiting
Richard A Pinkerton, DO, Phone: 724-349-9444
Richard A Pinkerton, DO, Sub-Investigator
Gopala A Raminen, MD, Sub-Investigator

UPMC Cancer Centers - Johnstown, Johnstown, Pennsylvania 15901, United States; Recruiting
Rahid A Awan, MD, Phone: 814-534-4724
Rashid A Awan, MD, Sub-Investigator
Michael D Voloshin, MD, Sub-Investigator

Hematology-Oncology Associates of UPCI, McKeesport, Pennsylvania 15132, United States; Recruiting
Kevin kane, MD, Phone: 412-664-2607
Kevin Kane, MD, Sub-Investigator
Dennis Brunskill, MD, Sub-Investigator

Hematology/Oncology - Private Practice, McKeesport, Pennsylvania 15132, United States; Recruiting
Dennis Brunskill, MD, Phone: 412-673-4453
Dennis Brunskill, MD, Sub-Investigator

UPMC Cancer Centers - Monroeville, Monroeville, Pennsylvania 15146, United States; Recruiting
Hyoung Kim, MD, Phone: 412-856-7110
Hyoung Kim, MD, Sub-Investigator

UPMC Cancer Centers - Arnold Palmer at Mt. Pleasant, Mt. Pleasant, Pennsylvania 15666, United States; Recruiting
John Waas, MD, Phone: 724-547-7092
John Waas, MD, Sub-Investigator

UPMC Cancer Centers - New Castle, New Castle, Pennsylvania 16105, United States; Recruiting
Lowell C Shinn, MD, Phone: 724-658-7300
Lowell C Shinn, MD, Sub-Investigator
Sheryl R Simon, MD, Sub-Investigator
William E Spielvogle, MD, Sub-Investigator

UPMC Cancer Centers - Drake, Pittsburgh, Pennsylvania 15241, United States; Recruiting
Louis Pietragallo, MD, Phone: 412-831-1320
Louis Pietragallo, MD, Sub-Investigator
Robert Volkin, MD, Sub-Investigator
Ronald Fierro, MD, Sub-Investigator

UPMC Cancer Centers - St. Margaret's, Pittsburgh, Pennsylvania 15215, United States; Recruiting
Peter G Ellis, MD, Phone: 412-781-3744
Peter G Ellis, MD, Sub-Investigator
Mark S Georgiadis, MD, Sub-Investigator
Min Sun, MD, Sub-Investigator
Daniel P Petro, MD, Sub-Investigator

UPMC Cancer Centers - Hillman Cancer Center, Pittsburgh, Pennsylvania 15232, United States; Recruiting
Suzanne Lentzsch, MD, PhD, Phone: 412-648-6586
Stanley M Marks, MD, Sub-Investigator
Jeffrey E Shogan, MD, Sub-Investigator
Mounzer E Agha, MD, Sub-Investigator
Anastasios Raptis, MD, Sub-Investigator
Barry C Lembersky, MD, Sub-Investigator
David M Friedland, MD, Sub-Investigator
Dennis J Meisner, MD, Sub-Investigator
Robert Redner, MD, Sub-Investigator
Michael Boyiadzis, MD, Sub-Investigator
Gurkamal Chatta, MD, Sub-Investigator
Samuel Jacobs, MD, Sub-Investigator
Ronald Stoller, MD, Sub-Investigator
Suzanne Lentzsch, MD, PhD, Principal Investigator
Markus Mapara, MD, PhD, Sub-Investigator
Jing-Zhou Hou, MD, Sub-Investigator

UPMC Cancer Centers - Passavant, Pittsburgh, Pennsylvania 15237, United States; Recruiting
Jennifer Osborn, MD, Phone: 412-367-6454
Jennifer Osborn, MD, Sub-Investigator

VA Healthcare System - 646, Pittsburgh, Pennsylvania 15240, United States; Recruiting
Garson D Roodman, MD, PhD, Phone: 412-688-6571
Garson D Roodman, MD, PhD, Sub-Investigator

UPMC Cancer Centers - Uniontown, Uniontown, Pennsylvania 15401, United States; Recruiting
Flavia E Kostov, MD, Phone: 724-439-8950
Flavia E Kostov, MD, Sub-Investigator
Sajid M Peracha, MD, Sub-Investigator
Afaq Ahmad, MD, Sub-Investigator

UPMC Cancer Centers - Washington, Washington, Pennsylvania 15301, United States; Recruiting
Alexis M Megaludis, MD, Phone: 724-223-3816
Alexis M Megaludis, MD, Sub-Investigator
Patrick L Kane, MD, Sub-Investigator
Mohammad P Rahman, MD, Sub-Investigator
Wayne Pfrimmer, MD, Sub-Investigator

UPMC Cancer Centers - North Hills, Wexford, Pennsylvania 15090, United States; Recruiting
Theodore L Crandall, MD, Phone: 412-367-1199
Theodore L Crandall, MD, Sub-Investigator
Robert J Gluckman, MD, Sub-Investigator
Kiran K Rajasenan, MD, Sub-Investigator

UPMC Cancer Centers - Windber, Windber, Pennsylvania 15963, United States; Recruiting
Rashid A Awan, MD, Phone: 814-467-5984
Rashid A Awan, MD, Sub-Investigator

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Starting date: February 2008
Last updated: August 10, 2010