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Multiple MyelomaPhase 1/2NCT01029054

Carfilzomib and Lenalidomide With Dexamethasone Combination in Newly Diagnosed, Previously Untreated Multiple Myeloma

A Phase 1/2 study testing carfilzomib, lenalidomide plus dexamethasone in people with Multiple Myeloma, run by University of Michigan Rogel Cancer Center at 4 sites in United States.

Completed

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

Official record
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Trial summary

This study is designed to evaluate the safety and to determine the maximum tolerated dose of carfilzomib + lenalidomide in combination with dexamethasone in newly diagnosed Multiple Myeloma patients who have not received treatment. 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?
carfilzomib, lenalidomide plus dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
4 sitesUnited States
Study dates
Sep 2009to Jul 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

  • Newly diagnosed, histologically confirmed, previously untreated Stage I, II, or III multiple myeloma requiring systemic chemotherapy
  • Diagnosis of symptomatic multiple myeloma per IMWG uniform criteria within the past 90 days
  • Measurable disease, per IMWG (International Myeloma Working Group) criteria (>= one of the following) within the past 4 weeks:
  • Monoclonal protein >= 0.5 g/dL by serum protein electrophoresis
  • Monoclonal light chain >= 200 mg by 24-hour urine protein electrophoresis
  • If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable
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  • Life expectancy > 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Adequate hepatic function, with bilirubin < 1.5 x the ULN, and AST (Aspartate Aminotransferase) and ALT (Alanine Transaminase) < 2.5 x ULN
  • Absolute neutrophil count (ANC) >=1.0 x 109/L, hemoglobin >= 8 g/dL, platelet count >= 75 x 109/L
  • Calculated creatinine clearance (by Cockroft-Gault) >= 60 ml/min
  • Written informed consent in accordance with federal, local, and institutional guidelines.
  • Subjects must agree to adhere to all study requirements, including birth control measures and pregnancy testing, visit schedule, outpatient treatment, required concomitant medications, and laboratory monitoring.
  • Must be able to take either 81 mg or 325 mg aspirin daily as prophylactic anticoagulation.

Who cannot join

  • Non-secretory or hyposecretory multiple myeloma, defined as <0.5 g/dL M-protein in serum, <200 mg/24 hr urine M-protein, or disease only measured by serum free light chain
  • POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes) syndrome
  • Plasma cell leukemia
  • Waldenström's macroglobulinemia or IgM myeloma
  • Radiotherapy to multiple sites or immunotherapy within 2 weeks before start of protocol treatment (localized radiotherapy to a single site at least 1 week before start is permissible)
  • Patient must not have been previously treated with any prior systemic therapy for the treatment of multiple myeloma
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  • Prior treatment of hypercalcemia or spinal cord compression or aggressively progressing myeloma with corticosteroids does not disqualify the patient (the dose should not exceed the equivalent of 160 mg of dexamethasone in a 2 week period)
  • Bisphosphonates are permitted
  • Participation in an investigational therapeutic study within 3 weeks or within 5 drug halflives (t1/2) prior to first dose, whichever time is greater
  • Pregnant or lactating females
  • History of allergy to mannitol
  • Major surgery within 3 weeks prior to first dose
  • Myocardial infarction within 3 months prior to enrollment, NYHA (New York Heart Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Uncontrolled hypertension or diabetes
  • Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
  • Known or suspected HIV infection, known HIV seropositivity
  • Active hepatitis infection
  • Non-hematologic malignancy within the past 3 years except a) adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone
  • Any clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
  • Significant neuropathy (Grade >2) at the time of the first dose and/or within 14 days before enrollment
  • Contraindication to any of the required concomitant drugs
  • Subjects in whom the required program of PO and IV fluid hydration is contraindicated
  • Subjects with known or suspected amyloidosis of any organ
  • Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Mt. Sinai Medical Center

    New York, New York, 10029

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Multicenter, Open-label, Single-arm, Phase 1b/2 Study of the Safety and Efficacy of Combination Treatment w/ Carfilzomib, Lenalidomide (Revlimid®) and Dexamethasone (CRD) in Subjects w/ Newly Diagnosed, Previously Untreated Multiple Myeloma Requiring Systemic Chemotherapy

This study is designed to evaluate the safety and to determine the maximum tolerated dose of carfilzomib + lenalidomide in combination with dexamethasone in newly diagnosed Multiple Myeloma patients who have not received treatment.

Read the detailed description

During the Phase I portion of this clinical trial, the dose of Revlimid® and carfilzomib will be increased until the best and safest amount (or dose) is identified in combination with standard doses of Revlimid® and dexamethasone. "Investigational" means that the drug combination is still being studied and that research doctors are trying to find out more about it such as the safest dose to use, the side effects it may cause and how effective the Revlimid® and carfilzomib and dexamethasone investigational combination is for treating newly diagnosed multiple myeloma. In this clinical trial we are looking for the highest dose of the combination that can be given safely and see how well it works as a combination in newly diagnosed patients.

The drug, carfilzomib, has not yet been approved by the FDA (U.S. Food and Drug Administration). Revlimid® and Dexamethasone have been approved by the FDA. The drugs have not been approved in this combination for use for your type of cancer or any other type of cancer. Carfilzomib is being researched to treat multiple myeloma. Dexamethasone is commonly used, either alone, or in combination with other drugs, to treat multiple myeloma. Revlimid® is currently approved by the US FDA in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least 1 prior therapy.

After the Phase I clinical trial defines the safest doses of Revlimid® and carfilzomib and dexamethasone that can be taken together, the research study will move on to its second portion, a Phase II clinical trial. The Phase II portion of the clinical trial will test the clinical effectiveness of the best dose combination of the three drugs.

Being tested
carfilzomib, lenalidomide plus dexamethasone
Keywords
Multiple Myeloma
Medical subject headings
Multiple Myeloma

What participants receive

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

  • carfilzomib, lenalidomide plus dexamethasoneDrug

    Phase I: Carfilzomib will be administered at the dosage assigned for the subject's cohort as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance).

    Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+.

    Dexamethasone 40 mg will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push.

  • carfilzomib, lenalidomide plus dexamethasoneDrug

    Phase II: Carfilzomib will be administered at the Maximum Tolerated Dose (MTD) established in Phase I as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance).

    Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+.

    Dexamethasone will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push on Days 1, 8, 15, and 22 as follows: Cycles 1-4: 40 mg; Cycles 5-8: 20 mg; and Cycles 9 and higher: 10 mg.

Study groups in NCT01029054
Study groupRoleWhat they receive
carfilzomib, lenalidomide w/dexamethasoneExperimentalPhase I: carfilzomib will be taken with a combination of lenalidomide plus dexamethasone in a series of escalating dosages to determine the maximum tolerated dose level Phase II: carfilzomib will be given at the MTD established in the Phase I portion of the study
Receives: Drug: carfilzomib, lenalidomide plus dexamethasone

What is being measured

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

  1. The Maximum Tolerated Dose (MTD) of Carfilzomib

    Determine the MTD of Carfilzomib when combined with Lenalidomide and Dexamethasone. The estimated time to determine the MTD is 6 months.

    Measured: 6 Months

  2. The Percentage of Patients That Achieve a Response to Treatment

    The percentage of patients that achieve at least a sCR (Stringent Complete Response), at least a VGPR (Very Good Partial Response) and at least a PR (Partial Response) will be determined.

    sCR is defined as:

    • Negative immunofixation on the serum and urine and
    • Disappearance of any soft tissue plasmacytomas and
    • < 5% plasma cells in bone marrow and
    • Normal SFLC ratio and
    • Absence of clonal cells in bone marrow

    VGPR is defined as:

    • Serum and urine M-protein detectable by immunofixation but not on electrophoresis or
    • ≥ 90% reduction in serum M-component with urine M-component < 100 mg per 24 hours

    PR is defined as:

    • ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours
    • If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required

    Measured: 4 Months After Treatment Start

Secondary outcomes (1)

  1. The Percentage of Patients Alive Without Progression

    The Progression Free Survival (PFS) rate will be determined at 12 and 24 months post treatment.

    Progressive Disease (PD) is defined as an increase of greater than or equal to 25% from lowest response level in serum M-component and/ or urine M-component and/ or the difference between involved or uninvolved SFLC levels and/ or bone marrow % plasma cells. PD may also be the development of new bone lesions or soft tissue plasmacytomas or the increase in size of existing lesions. PD may also be the development of hypercalcemia.

    Measured: 12 Months and 24 Months Post Treatment

Timeline

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

  1. First posted9 Dec 2009 (estimated)
  2. Study startSep 2009
  3. Primary completionDec 2011
  4. Study completionJul 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
Health services research
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01029054
Sponsor's protocol ID
UMCC 2009.056
Other IDs
HUM30396
Status last verified
Dec 2016
First submitted
8 Dec 2009
Last updated
30 Jan 2017
Data monitoring committee
Yes

Publications

  • Landgren O, Kazandjian D, Roussel M, Jasielec J, Dytfeld D, Anderson A, Kervin TA, Iskander K, McFadden I, Jakubowiak AJ. Efficacy and safety of carfilzomib-lenalidomide-dexamethasone in newly diagnosed multiple myeloma: pooled analysis of four single-arm studies. Leuk Lymphoma. 2022 Oct;63(10):2413-2421. doi: 10.1080/10428194.2022.2068001. Epub 2022 May 12.

    PubMed 35549810

  • Jakubowiak AJ, Dytfeld D, Griffith KA, Lebovic D, Vesole DH, Jagannath S, Al-Zoubi A, Anderson T, Nordgren B, Detweiler-Short K, Stockerl-Goldstein K, Ahmed A, Jobkar T, Durecki DE, McDonnell K, Mietzel M, Couriel D, Kaminski M, Vij R. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012 Aug 30;120(9):1801-9. doi: 10.1182/blood-2012-04-422683. Epub 2012 Jun 4.

    PubMed 22665938

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing carfilzomib, lenalidomide plus dexamethasone in people with Multiple Myeloma, run by University of Michigan Rogel Cancer Center at 4 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 14 inclusion and 24 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 30 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 20 Nov 2014). 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?

The Maximum Tolerated Dose (MTD) of Carfilzomib (time frame: 6 Months). 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 NCT01029054, which also lists 2 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 30 Jan 2017.

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