AzTrials
AzTrials

Refractory Multiple MyelomaPhase 1/2NCT01049945

Bendamustine Hydrochloride, Lenalidomide, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma

A Phase 1/2 study testing bendamustine hydrochloride, lenalidomide and dexamethasone in people with Refractory Multiple Myeloma, run by Mayo Clinic at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

RATIONALE: Drugs used in chemotherapy, such as bendamustine hydrochloride and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Refractory Multiple Myeloma
What is being tested?
bendamustine hydrochloride, lenalidomide and dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
5 sitesUnited States
Study dates
Feb 2010to 16 Sep 2015
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Diagnosis of MM and documentation of at least 1 prior therapy (induction therapy followed by stem cell transplantation is considered one prior therapy) but not more than two previous therapies
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide
  • Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
  • Able to take aspirin (325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA or at high risk of developing thrombosis may use warfarin or low molecular weight heparin)
  • AST (SGOT) and ALT (SGPT) =< 3.0 x upper limit of normal (ULN)
Show all 15Show fewer
  • Creatinine clearance >= 60 mL/min (Cockcroft-Gault calculation) for patients enrolled in Phase 1 and Creatinine clearance >= 30 mL/min (Cockcroft-Gault calculation) for patients enrolled in phase 2 portion
  • Patients with measurable disease, defined by any of the following: serum monoclonal protein >= 1.0 g by protein electrophoresis; > 200 mg of monoclonal protein in the urine on 24-hour electrophoresis; serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio; or monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)
  • All necessary baseline studies for determining eligibility must be obtained within 21 days prior to enrollment
  • Subject has an ECOG =< 2 OR Karnofsky >= 60% performance status; patients with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible
  • FCBP must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing
  • Absolute neutrophil count (ANC) >= 1,000 cells/dL (1.0 x 10^9/L) (growth factors cannot be used within 14 days of first drug administration)
  • Untransfused platelet count >= 75,000 cells/dL (50 x 10^9/L) for patients in whom < 50% of bone marrow nucleated cells are plasma cells; but platelet count >=50,000/dL for patients in whom 50% of bone marrow nucleated cells are plasma cells
  • Total Bilirubin =< 1.5 mg/dL
  • Hemoglobin >= 8.0 g/dl

Who cannot join

  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
  • Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but no more than 10 mg p.o. q.d. or its equivalent) for symptom management and comorbid conditions; doses of corticosteroid should be stable for at least 7 days prior to study treatment
  • Prior radiation therapy within 2 weeks of the first dose of study treatment
  • Known active infection requiring parenteral or oral anti-infective treatment
  • Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation
  • Patient has hypersensitivity to any of the components of study therapy - Known HIV or active hepatitis B or C viral infection
Show all 14Show fewer
  • Known hypersensitivity to required prophylactic medications
  • Patient has received other investigational drugs within 14 days before enrollment
  • Pregnant or breast-feeding females (lactating females must agree not to breast feed while taking lenalidomide)
  • Subjects with evidence of mucosal or internal bleeding and/or platelet transfusion refractory (i.e., unable to maintain a platelet count >= 50,000 cells/mm^3)
  • Concurrent therapy with a marketed or investigational anticancer therapy
  • Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient
  • Other investigational agents are not to be used during the study
  • Prior peripheral stem cell transplant within 12 weeks of the first dose of study treatment

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Chicago

    Chicago, Illinois, 60637-1470

  • City of Hope

    Duarte, California, 91010

  • Mayo Clinic in Florida

    Jacksonville, Florida, 55904

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Washington Universtiy School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase I/II, Multicenter, Open-label, Dose-escalation Study of Bendamustine in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma

RATIONALE: Drugs used in chemotherapy, such as bendamustine hydrochloride and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Giving bendamustine hydrochloride together with lenalidomide and dexamethasone may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of bendamustine hydrochloride and lenalidomide when given together with dexamethasone and to see how well they work in treating patients with relapsed multiple myeloma.

Read the detailed description

PRIMARY OBJECTIVES: I. To determine the Maximum Tolerated Dose (MTD) of bendamustine and lenalidomide in combination with dexamethasone in subjects with Multiple Myeloma (MM) in first or second relapse. (Phase I) II. To evaluate the confirmed response rate of bendamustine in combination with lenalidomide and dexamethasone in subjects with MM in first or second relapse. (Phase II) SECONDARY OBJECTIVES: I. To evaluate the safety of bendamustine in combination with lenalidomide and dexamethasone. (Phase I and II) II. To evaluate time-to-tumor-progression, progression-free survival, duration of response, and overall survival. (Phase II) OUTLINE: This is a phase I dose escalation study of bendamustine hydrochloride and lenalidomide followed by a phase II study. Patients receive dexamethasone orally or IV on days 1, 8, 15, and 22; bendamustine hydrochloride IV over 30 minutes on days 1 and 2; and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving at least stable disease after 6 courses may continue to receive lenalidomide and dexamethasone as above in the absence of disease progression or unacceptable toxicity. Dexamethasone may be discontinued after 12 courses of therapy at the treating investigator's discretion. After completion of study treatment, patients are followed at 4 weeks and then periodically for up to 2 years.

Being tested
bendamustine hydrochloride, lenalidomide, dexamethasone
Medical subject headings
Multiple Myeloma

What participants receive

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

  • bendamustine hydrochlorideDrug

    Also called bendamustin hydrochloride, bendamustine, cytostasan hydrochloride, Ribomustin

    Given IV

  • lenalidomideDrug

    Also called CC-5013, IMiD-1, Revlimid

    Given orally

  • dexamethasoneDrug

    Also called Aeroseb-Dex, Decaderm, Decadron, Decaspray

    Given orally or IV

Study groups in NCT01049945
Study groupRoleWhat they receive
Arm IExperimentalPatients receive dexamethasone orally or IV on days 1, 8, 15, and 22; bendamustine hydrochloride IV over 30 minutes on days 1 and 2; and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: bendamustine hydrochloride; Drug: lenalidomide; Drug: dexamethasone

What is being measured

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

  1. Dose Limiting Toxicity of Bendamustine Hydrochloride and Lenalidomide in Combination With Dexamethasone (Phase I)

    The Maximum Tolerated Dose (MTD) is the dose level below that at which a dose limiting toxicity (DLT) is observed in ≥ 33% (i.e., ≥ 2 of 6) subjects in a cohort. A dose limiting toxicity is defined as one of the following adverse events in the Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 deemed at least possibly related to treatment:

    • Grade 2 neuropathy with pain
    • Any grade 3 Non-Hematologic toxicity
    • Any grade Non-Hematologic event requiring a dose reduction in cycle 1 or delaying the next cycle by >14 days.
    • Grade 4 neutropenia
    • Febrile neutropenia
    • Grade 4 thrombocytopenia
    • Grade 3 thrombocytopenia associated with bleeding
    • Any Hematologic event requiring a dose reduction in cycle 1 or a delay in the next cycle of treatment by >14 days.

    We are reporting the results of this endpoint as the number of DLTs per dose level.

    Measured: One cycle of treatment

  2. Confirmed Response Rate (Dose Level 4) Reported as the Percentage of Patients Achieving a Confirmed Response (sCR, CR, VGPR, or PR).

    Complete response (CR)

    • Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow.

    Stringent complete response (sCR) - A CR plus normal FLC ratio and no clonal cells in bone marrow

    Near complete response (nCR) A CR, with the persistence of original monoclonal protein

    Very good partial response (VGPR)

    • Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-component plus urine M-component <100 mg per 24 h

    Partial response (PR)

    • ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h.
    • a ≥50% decrease in the difference between involved and uninvolved FLC levels
    • or a ≥50% reduction in plasma cells is required in place of M-protein, if ≥30% at baseline.

    Measured: Up to 6 cycles of treatment

Secondary outcomes (4)

  1. Duration of Response (DOR) (Phase II)

    DOR is the time from the date the patient's objective status is first noted to be PR or better to the earliest date of progression (PD=Increase of > 25% from lowest response value in Serum/Urine M-component) is documented. Treatment response was assessed using the International Myeloma Working Group uniform criteria. Complete response (CR)=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. Stringent complete response (sCR)=A CR plus normal FLC ratio and no clonal cells in bone marrow. Near complete response (nCR)=A CR, with the persistence of original monoclonal protein. Very good partial response (VGPR) =Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-component plus urine M-component <100 mg per 24 h, Partial response (PR)=≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h.

    Measured: Up to 2 years from study completion

  2. Event Free Survival (Phase II)

    The event-free survival time is defined as the time from registration to disease progression (PD=Increase of > 25% from lowest response value in Serum/Urine M-component) while receiving bendamustine, lenalidomide, and dexamethasone, death due to any cause, or subsequent treatment for multiple myeloma. The distribution of event-free survival will be estimated using the method of Kaplan-Meier. Treatment response was assessed using the International Myeloma Working Group uniform criteria.

    Measured: Up to 2 years from study completion

  3. Progression Free Survival (Phase II)

    The progression-free survival time is defined as the time from registration to disease progression (PD=Increase of > 25% from lowest response value in Serum/Urine M-component) while receiving bendamustine, lenalidomide, and dexamethasone or death due to any cause, whichever comes first. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. Treatment response was assessed using the International Myeloma Working Group uniform criteria.

    Measured: Up to 2 years from study completion

  4. Overall Survival (Phase II)

    The overall survival time is defined as the time from registration to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier. The overall survival rate at 6 months is defined as the percentage of participants who are alive at 6 months.

    Measured: at 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 posted15 Jan 2010 (estimated)
  2. Study startFeb 2010
  3. Primary completionNov 2012
  4. Study completion16 Sep 2015

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
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01049945
Sponsor's protocol ID
MMRC-020-021
Other IDs
NCI-2009-01535, MMRC-020-021, 09-004211, C18083/6125
Status last verified
Apr 2016
First submitted
14 Jan 2010
Last updated
11 Feb 2020
Data monitoring committee
Yes

Publications

  • Kumar SK, Krishnan A, LaPlant B, Laumann K, Roy V, Zimmerman T, Gertz MA, Buadi FK, Stockerl Goldstein K, Birgin A, Fiala M, Duarte L, Maharaj M, Levy J, Vij R. Bendamustine, lenalidomide, and dexamethasone (BRD) is highly effective with durable responses in relapsed multiple myeloma. Am J Hematol. 2015 Dec;90(12):1106-10. doi: 10.1002/ajh.24181. Epub 2015 Oct 6.

    PubMed 26331432

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing bendamustine hydrochloride, lenalidomide and dexamethasone in people with Refractory Multiple Myeloma, run by Mayo Clinic at 5 sites in United States.

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 15 inclusion and 14 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: finished, as of the sponsor's last update on 11 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. 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?

Yes. Results are posted in the registry (first posted 30 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity of Bendamustine Hydrochloride and Lenalidomide in Combination With Dexamethasone (Phase I) (time frame: One cycle of treatment). The study lists 2 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 NCT01049945, which also lists 1 linked publication.

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 11 Feb 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in