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Multiple MyelomaPhase 1/2NCT01686386

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

A Phase 1/2 study testing Bendamustine, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Gruppo Italiano Studio Linfomi at 1 site in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Bendamustine, Lenalidomide and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteItaly
Study dates
Feb 2010to Oct 2013
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

1 site in 1 country.

Fortunato Morabito, MD contact

+390984681329

fortunato_morabito@tin.it

Fortunato Morabito, MD contact

+390984681539

fortunato_morabito@tin.it

Italy1 site, 1 recruiting

  • U. O. C. Ematologia - Azienda Ospedaliera Cosenza

    Cosenza, Cosenza, 87100

    Fortunato Morabito, MD, +390984681329, fortunato_morabito@tin.it

    Recruiting

Other trials in Italy

About this study

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

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.

Read the 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.

Keywords
Relapsed, Multiple Myeloma, Lenalidomide, Bendamustine
Medical subject headings
Multiple Myeloma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BendamustineDrug

    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.

  • LenalidomideDrug

    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.

  • DexamethasoneDrug

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

Study groups in NCT01686386
Study groupRoleWhat they receive
Dose escalation benda lena dexaExperimentalPhase 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.
Receives: Drug: Bendamustine; Drug: Lenalidomide; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: up to 28 days during first cycle

  2. Phase I:Determination of occurrence rate of AE/SAEs

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

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

  3. 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.

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

Secondary outcomes (4)

  1. Phase I: Assessment of the preliminary antineoplastic properties of the BdL

    To explore the preliminary antitumor activity of drug combination in patients with relapsed MM

    Measured: after an avarage of 6 months

  2. Phase II: AE/SAEs

    To define the safety profile of the treatment assessing the occurrence rate and the severity

    Measured: Every 28 days (during all cycles)

  3. Phase II:Determination of the response rates

    To assess Partial Response and Complete Response rates

    Measured: Assessed after 6 months

  4. Phase II:Time to Event parameters

    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)

    Measured: avarage 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2012 (estimated)
  2. Study startFeb 2010
  3. Primary completionApr 2012
  4. Study completionOct 2013 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01686386
Sponsor's protocol ID
RV-MM-GIMEMA/GISL430
Other IDs
2010-018336-40
Status last verified
Apr 2013
First submitted
31 Jul 2012
Last updated
5 Apr 2013
Results posted
No
Data monitoring committee
No

Publications

  • 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.

  • Jemal A, Thomas A, Murray T, Thun M. Cancer statistics, 2002. CA Cancer J Clin. 2002 Jan-Feb;52(1):23-47. doi: 10.3322/canjclin.52.1.23.

    PubMed 11814064

  • Durie BG. The epidemiology of multiple myeloma. Semin Hematol. 2001 Apr;38(2 Suppl 3):1-5. doi: 10.1016/s0037-1963(01)90087-3.

    PubMed 11309701

  • Kishi Y, Oki Y, Machida U. Thalidomide in multiple myeloma. N Engl J Med. 2000 Mar 30;342(13):975; author reply 975-6. doi: 10.1056/NEJM200003303421313. No abstract available.

    PubMed 10744492

  • Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, Siegel D, Borrello I, Rajkumar SV, Chanan-Khan AA, Lonial S, Yu Z, Patin J, Olesnyckyj M, Zeldis JB, Knight RD; Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007 Nov 22;357(21):2133-42. doi: 10.1056/NEJMoa070596.

    PubMed 18032763

  • Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foa R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD; Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007 Nov 22;357(21):2123-32. doi: 10.1056/NEJMoa070594.

    PubMed 18032762

  • Palumbo A, Falco P, Corradini P, Falcone A, Di Raimondo F, Giuliani N, Crippa C, Ciccone G, Omede P, Ambrosini MT, Gay F, Bringhen S, Musto P, Foa R, Knight R, Zeldis JB, Boccadoro M, Petrucci MT; GIMEMA--Italian Multiple Myeloma Network. Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA--Italian Multiple Myeloma Network. J Clin Oncol. 2007 Oct 1;25(28):4459-65. doi: 10.1200/JCO.2007.12.3463. Epub 2007 Sep 4.

    PubMed 17785703

  • Anger G, Hesse P, Baufeld H. [Treatment of multiple myeloma with a new cytostatic agent: gamma-l-methyl-5-bis-(beta-chlorethyl)-amino-benzimidazolyl-(2)-butyric acid hydrochloride]. Dtsch Med Wochenschr. 1969 Nov 28;94(48):2495-500. doi: 10.1055/s-0028-1110470. No abstract available. German.

    PubMed 4903552

  • Leoni LM, Bailey B, Reifert J, Bendall HH, Zeller RW, Corbeil J, Elliott G, Niemeyer CC. Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents. Clin Cancer Res. 2008 Jan 1;14(1):309-17. doi: 10.1158/1078-0432.CCR-07-1061.

    PubMed 18172283

  • Ponisch W, Mitrou PS, Merkle K, Herold M, Assmann M, Wilhelm G, Dachselt K, Richter P, Schirmer V, Schulze A, Subert R, Harksel B, Grobe N, Stelzer E, Schulze M, Bittrich A, Freund M, Pasold R, Friedrich T, Helbig W, Niederwieser D; East German Study Group of Hematology and Oncology (OSHO). Treatment of bendamustine and prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with melphalan and prednisone--a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO). J Cancer Res Clin Oncol. 2006 Apr;132(4):205-12. doi: 10.1007/s00432-005-0074-4. Epub 2006 Jan 10.

    PubMed 16402269

  • Ponisch W, Rozanski M, Goldschmidt H, Hoffmann FA, Boldt T, Schwarzer A, Ritter U, Rohrberg R, Schwalbe E, Uhlig J, Zehrfeld T, Schirmer V, Haas A, Kreibich U, Niederwieser D; East German Study Group of Haematology and Oncology (OSHO). Combined bendamustine, prednisolone and thalidomide for refractory or relapsed multiple myeloma after autologous stem-cell transplantation or conventional chemotherapy: results of a Phase I clinical trial. Br J Haematol. 2008 Oct;143(2):191-200. doi: 10.1111/j.1365-2141.2008.07076.x. Epub 2008 Aug 24.

    PubMed 18752593

  • List A, Kurtin S, Roe DJ, Buresh A, Mahadevan D, Fuchs D, Rimsza L, Heaton R, Knight R, Zeldis JB. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005 Feb 10;352(6):549-57. doi: 10.1056/NEJMoa041668.

    PubMed 15703420

  • List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, Powell B, Greenberg P, Thomas D, Stone R, Reeder C, Wride K, Patin J, Schmidt M, Zeldis J, Knight R; Myelodysplastic Syndrome-003 Study Investigators. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006 Oct 5;355(14):1456-65. doi: 10.1056/NEJMoa061292.

    PubMed 17021321

  • Raza A, Reeves JA, Feldman EJ, Dewald GW, Bennett JM, Deeg HJ, Dreisbach L, Schiffer CA, Stone RM, Greenberg PL, Curtin PT, Klimek VM, Shammo JM, Thomas D, Knight RD, Schmidt M, Wride K, Zeldis JB, List AF. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood. 2008 Jan 1;111(1):86-93. doi: 10.1182/blood-2007-01-068833. Epub 2007 Sep 24.

    PubMed 17893227

  • 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Bendamustine, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Gruppo Italiano Studio Linfomi at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 5 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Fortunato Morabito, MD (+390984681329, fortunato_morabito@tin.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I:Determination of Maximum Tolerated Dose (time frame: up to 28 days during first cycle). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01686386, which also lists 25 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2013.

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