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Trial Title:
Study of Bendamustine, Lenalidomide and Low-dose Dexamethasone, for the Treatment of Patients With Relapsed Myeloma
NCT ID:
NCT01686386
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Dexamethasone
Lenalidomide
Bendamustine Hydrochloride
Conditions: Keywords:
Relapsed
Multiple Myeloma
Lenalidomide
Bendamustine
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Unknown status
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Bendamustine
Description:
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.
Arm group label:
Dose escalation benda lena dexa
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
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.
Arm group label:
Dose escalation benda lena dexa
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Phase I and Phase II Dexamethasone fixed dose 40 mg/die
Arm group label:
Dose escalation benda lena dexa
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.
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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
U. O. C. Ematologia - Azienda Ospedaliera Cosenza
Address:
City:
Cosenza
Zip:
87100
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Fortunato Morabito, MD
Phone:
+390984681329
Email:
fortunato_morabito@tin.it
Start date:
February 2010
Completion date:
October 2013
Lead sponsor:
Agency:
Gruppo Italiano Studio Linfomi
Agency class:
Other
Source:
Gruppo Italiano Studio Linfomi
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT01686386