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A Phase I/II Study of Bendamustine, Lenalidomide and Low-dose Dexamethasone, (BdL) for the Treatment of Patients With Relapsed Myeloma.

Phase 1/Phase 2
18 Years
Open (Enrolling)
Multiple Myeloma

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Trial Information

A Phase I/II Study of Bendamustine, Lenalidomide and Low-dose Dexamethasone, (BdL) for the Treatment of Patients With Relapsed Myeloma.

Multiple myeloma is a B-cell malignancy resulting from the monoclonal proliferation of
plasma cells within the bone marrow. According to the American Cancer Society, 14,600 new
cases of multiple myeloma will be diagnosed in 2002, and these will account for
approximately 1% of all new cancer cases. Multiple myeloma will contribute to 2% of all
cancer deaths this year; an estimated 10,800 deaths will occur overall. The disease is more
prevalent in men and is twice as common in African-Americans as in Caucasians. Multiple
myeloma is commonly thought of as a disease of older patients; the median age at diagnosis
is 68 years, and the incidence increases more than 4%/year in those older than 85 years. The
median survival with standard treatment is only 3 years.

Therapeutic options for patients with multiple myeloma (MM) are rapidly changing. The
emergence of two highly active novel agents, bortezomib and lenalidomide, have dramatically
changed the landscape of treatment options and have improved outcomes for many patients.
Combinations of conventional agents with novel agents have also demonstrated significant
efficacy for patients with newly diagnosed and relapsed myeloma. Among the conventional
agents that are being explored is the bifunctional alkylator agent bendamustine, which has
demonstrated single-agent activity and activity with novel agents.

Lenalidomide is a new immunomodulating agent effective in multiple myeloma, especially when
associated with dexamethasone or melphalan and prednisone. The role of lenalidomide in the
treatment of relapsed/refractory patients with MM has been established and current research
is focused on the combination of lenalidomide with chemotherapy to further improve results.

Bendamustine is a bi-functional alkylating agent with a purine- like benzimidazole ring that
has been administered successfully to patients with MM. In vitro studies showed that
bendamustine possesses a unique profile of activity, which was clearly divergent from other
common nitrogen mustard drugs. Bendamustine and prednisone in newly diagnosed MM patients
results in superior complete response rate, prolonged time to treatment failure and improved
quality of life compared to treatment with melphalan and prednisone. The role of
bendamustine, thalidomide and prednisolone (BPT) in patients with relapsed or refractory
diseases stage II/III has been investigated by the East German Study group of Hematology and
Oncology (OSHO). The response rate was higher than 80%.

Despite the impressive efficacy of the lenalidomide/dexamethasone in relapsed MM, treated
patients will eventually relapse (median Time to Progression (TTP) is expected to be nearly
a year according the results of the two phase III randomized studies). Combination with an
effective novel agent as bendamustine could further increase both the response rate and the
TTP of lenalidomide/dexamethasone and induce durable responses in relapsed or refractory MM
patients. The identification of an appropriate lenalidomide dose to be adopted in
combination with bendamustine and dexamethasone and the generation of exploratory data on
the efficacy of this novel combination appears to be important in terms of future
development of even more effective treatments of MM.

Inclusion Criteria:

- Voluntary written informed consent

- Men and women age ≥ 18 years

- Female subjects are either post-menopausal or surgically sterilized or willing to use
2 simultaneous methods of contraception

- Male patients must agree to use a latex condom during sexual contact with females of
childbearing potential throughout the study and for at least 28 days following
discontinuation of lenalidomide;

- Confirmed diagnosis of Multiple Myeloma with measurable disease .Patients with
evidence of relapsed disease after more than 1 and equal but not more than 3 prior
lines of therapy.

- ECOG Performance Status 0 - 2

- Required baseline haematology and chemistry parameters

Exclusion Criteria:

- Myocardial infarction within 6 months prior to enrollment or has NYHA class III or IV
heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or
electrocardiographic evidence of acute ischemia or active conduction system

- Female subjects either pregnant or breast-feeding (negative serum β-human chorionic
gonadotropin (β-hCG) pregnancy test result)

- Patients have received other investigational drugs with 14 days before enrollment.

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study.

- Any of the following laboratory abnormalities:

Absolute neutrophil count (ANC) <1,000 /μl (1x109 /L) Untransfused platelet count <
50,0000cell/μl (50x109 /L) Serum SGOT/AST or SGPT/ALT > 2.0 upper limit of normal (ULN)
Total bilirubin > 2.0 mg/dL Renal insufficiently (serum creatinine level > 2.5 mg/dl or
Creatinine clearance < 30 mL/min calculated by Cockcroft-Gault estimation)

- Patients with active infections are ineligible.

- Patients who are HIV positive are ineligible.

- Patients with active leptomeningeal involvement are ineligible.

- Patients with a history of previous CSF tumor involvement without symptoms or signs
are eligible provided the CSF is now free of disease on lumbar puncture, and MRI of
the brain shows no tumor involvement.

- History of other malignancies within 3 years prior to study entry except for
adequately treated carcinoma in situ of the cervix or basal or squamous cell skin
cancer or breast, low grade, early stage localized prostate cancer treated surgically
with curative intent (TNM stage of T1a or T1b),

- Patients with uncontrolled insulin-dependent diabetes mellitus or uncompensated major
thyroid or adrenal dysfunction are ineligible.

- Patients with an ECOG performance status of > 2 are ineligible.

- Malabsorption syndrome or uncontrolled gastrointestinal toxicities

- Clinically significant pleural effusion in the previous 12 months or current ascitis

- Clinically-significant coagulation or platelet function disorder

- Intolerance to bendamustine and/or lenalidomide

Type of Study:


Study Design:

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

Outcome Measure:

Phase I:Determination of Maximum Tolerated Dose

Outcome Description:

In the first phase of the study, the dose of Bendamustine and Lenalidomide given with will be gradually escalated to reach the Maximum Tolerated Dose. The Maximum Tolerated Dose of Bendamustine and Lenalidomide will be evaluated during the first course (cycle 1) of Bendamustine Dexamethasone Lenalidomide (BdL) administered

Outcome Time Frame:

up to 28 days during first cycle

Safety Issue:


Principal Investigator

Fortunato Morabito, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Unità Operativa Complessa di Ematologia- Stabilimento Ospedaliero Annunziata - Azienda Ospedaliera di Cosenza


Italy: National Institute of Health

Study ID:




Start Date:

February 2010

Completion Date:

October 2013

Related Keywords:

  • Multiple Myeloma
  • Relapsed
  • Multiple Myeloma
  • Lenalidomide
  • Bendamustine
  • Multiple Myeloma
  • Neoplasms, Plasma Cell