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

NCT01686386 | Unknown Phase 1

• 2 other identifiers: RV-MM-GIMEMA/GISL4302010-018336-40
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Keywords

Relapsed; Multiple Myeloma; Lenalidomide; Bendamustine

Outcome Measures

Primary Outcomes (3)

• Phase I:Determination of Maximum Tolerated Dose

  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

  up to 28 days during first cycle

• Phase I:Determination of occurrence rate of AE/SAEs

  To assess the Safety and Toxicity of the Bendamustine,Dexamethasone and Lenalidomide (BdL) regimen

  up to 28 day (during the first cycle 1of BdL administered)

• Phase II: Overall Response Rate (ORR)

  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.

  An avarage of 6 months (after 6 cycles of therapy)

Secondary Outcomes (4)

• Phase I: Assessment of the preliminary antineoplastic properties of the BdL

  after an avarage of 6 months

• Phase II: AE/SAEs

  Every 28 days (during all cycles)

• Phase II:Determination of the response rates

  Assessed after 6 months

• Phase II:Time to Event parameters

  avarage 6 months

Study Arms (1)

Dose escalation benda lena dexa

EXPERIMENTAL

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; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Bendamustine DRUG

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.

Dose escalation benda lena dexa

Lenalidomide DRUG

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.

Dose escalation benda lena dexa

Dexamethasone DRUG

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

Dose escalation benda lena dexa

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gruppo Italiano Studio Linfomi: lead

Study Sites (1)

U. O. C. Ematologia - Azienda Ospedaliera Cosenza

Cosenza, Cosenza, 87100, Italy

RECRUITING

Related Publications (25)

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  PMID: 27442600 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

Bendamustine Hydrochloride; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

Study Officials

• Fortunato Morabito, MD

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

  STUDY CHAIR

Central Study Contacts

Fortunato Morabito, MD

CONTACT

+390984681329; fortunato_morabito@tin.it

Fortunato Morabito, MD

CONTACT

+390984681539; fortunato_morabito@tin.it

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2012
• First Posted: September 18, 2012
• Study Start: February 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: October 1, 2013
• Last Updated: April 5, 2013

Record last verified: 2013-04

Locations

IT (1)