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Study of Bendamustine, Lenalidomide and Low-dose Dexamethasone, for the Treatment of Patients With Relapsed Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01686386
Recruitment Status : Unknown
Verified April 2013 by Gruppo Italiano Studio Linfomi.
Recruitment status was:  Recruiting
First Posted : September 18, 2012
Last Update Posted : April 5, 2013
Information provided by (Responsible Party):
Gruppo Italiano Studio Linfomi

Brief Summary:
This is an open Label, Phase I/II, multicenter study. In the first phase it defines the maximum tolerated dose (MTD) of Bendamustine (B) given in combination with Lenalidomide (L) and low-dose Dexamethasone (d) and in the second phase it evaluates the antitumour activity of Bendamustine, Lenalidomide and Low-dose Dexamethasone (BdL) given in combination, in relapsed multiple myeloma patients.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Bendamustine Drug: Lenalidomide Drug: Dexamethasone Phase 1 Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Bendamustine, Lenalidomide and Low-dose Dexamethasone, (BdL) for the Treatment of Patients With Relapsed Myeloma.
Study Start Date : February 2010
Actual Primary Completion Date : April 2012
Estimated Study Completion Date : October 2013

Arm Intervention/treatment
Experimental: Dose escalation benda lena dexa

Phase I: Participants will be treated in groups (cohorts) of three to six subjects per cohort, according to a modified Fibonacci design. The dose of Bendamustine and Lenalidomide (from 0 to 5) will be increased from one cohort to the next. Regardless of the treatment cohort, participants will receive treatment in cycles lasting 28 days. In the first phase of the study, the dose of B and L given with will be gradually escalated to reach the MTD.

Phase II: Dexamethasone will be given in combination with the MTD of Bendamustine and Lenalidomide in cycles lasting 28 days.

Drug: Bendamustine
Phase I: dose escalation of Bendamustine Phase II: Dexamethasone will be given in combination with the MTD of Bendamustine and Lenalidomide in cycles lasting 28 days.

Drug: Lenalidomide
Phase I: dose escalation of Lenalidomide Phase II: Dexamethasone will be given in combination with the Maximum Tolerated Dose (MTD) of Bendamustine and Lenalidomide in cycles lasting 28 days.

Drug: Dexamethasone
Phase I and Phase II Dexamethasone fixed dose 40 mg/die

Primary Outcome Measures :
  1. Phase I:Determination of Maximum Tolerated Dose [ Time Frame: up to 28 days during first cycle ]
    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

  2. Phase I:Determination of occurrence rate of AE/SAEs [ Time Frame: up to 28 day (during the first cycle 1of BdL administered) ]
    To assess the Safety and Toxicity of the Bendamustine,Dexamethasone and Lenalidomide (BdL) regimen

  3. Phase II: Overall Response Rate (ORR) [ Time Frame: An avarage of 6 months (after 6 cycles of therapy) ]
    To assess the antitumour activity of the BdL regimen, in term of Complete response, Partial response and Stable disease, according to the best schedule identified during Phase I.

Secondary Outcome Measures :
  1. Phase I: Assessment of the preliminary antineoplastic properties of the BdL [ Time Frame: after an avarage of 6 months ]
    To explore the preliminary antitumor activity of drug combination in patients with relapsed MM

  2. Phase II: AE/SAEs [ Time Frame: Every 28 days (during all cycles) ]
    To define the safety profile of the treatment assessing the occurrence rate and the severity

  3. Phase II:Determination of the response rates [ Time Frame: Assessed after 6 months ]
    To assess Partial Response and Complete Response rates

  4. Phase II:Time to Event parameters [ Time Frame: avarage 6 months ]
    To evaluate the efficacy of the BdL regimen in patients with relapsed MM, in terms of Progression-Free Survival, Time to Progression, Time to Response, Duration of Response ,Overall Survival(PFS, TTP, TTR, DR, OS)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 abnormalities.
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01686386

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Contact: Fortunato Morabito, MD +390984681329
Contact: Fortunato Morabito, MD +390984681539

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U. O. C. Ematologia - Azienda Ospedaliera Cosenza Recruiting
Cosenza, Italy, 87100
Contact: Fortunato Morabito, MD    +390984681329   
Sponsors and Collaborators
Gruppo Italiano Studio Linfomi
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Study Chair: Fortunato Morabito, MD Unità Operativa Complessa di Ematologia- Stabilimento Ospedaliero Annunziata - Azienda Ospedaliera di Cosenza
Munshi NC, Tricot G, Barlogie B. Plasma cell neoplasms. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology, 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2001:2465-99.
Rajkumar SV, Jacobus S, Callander N et al. Phase III trial of lenalidomide plus high- dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): A trial coordinated by the Eastern Cooperative Oncology GroupJournal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 25, No 18S (June 20 Supplement), 2007.
Rajkumar SV, Jacobus S, Callander N et al. A Randomized Trial of Lenalidomide Plus High-Dose Dexamethasone (RD) Versus Lenalidomide Plus Low-Dose Dexamethasone (Rd) in Newly Diagnosed Multiple Myeloma (E4A03): A Trial Coordinated by the Eastern Cooperative Oncology Group.
Rummel MJ, von Gruenhagen U, Niederle N, et al: Bendamustine plus rituximab versus CHOP plus rituximab in the first-line treatment of patients with indolent and mantle-cell lymphomas: The first interim results of a randomized phase III study ofthe StiL (Study Group Indolent Lymphomas, Germany). Blood 110:120a, 2007 (abstr 385).

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Gruppo Italiano Studio Linfomi Identifier: NCT01686386    
Other Study ID Numbers: RV-MM-GIMEMA/GISL430
2010-018336-40 ( EudraCT Number )
First Posted: September 18, 2012    Key Record Dates
Last Update Posted: April 5, 2013
Last Verified: April 2013
Keywords provided by Gruppo Italiano Studio Linfomi:
Multiple Myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bendamustine Hydrochloride
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Angiogenesis Inhibitors