Multiple Myeloma and Plasma Cell NeoplasmPhase 1/2NCT00477750
Melphalan, Prednisone, and Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma
A Phase 1/2 study testing lenalidomide, melphalan and prednisone in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Mayo Clinic at 3 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as melphalan, prednisone, and lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- lenalidomide, melphalan and prednisone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 3 sitesUnited States
- Study dates
- Jun 2005to 5 Aug 2013
- 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
DISEASE CHARACTERISTICS:
- Diagnosis of multiple myeloma
- Newly diagnosed disease
- Requires treatment, in the judgment of the treating physician
- Not a candidate for (or patient declines) autologous stem cell transplantation
- Meets 1 of the following criteria:
- Measurable disease, defined by any of the following:
- Serum monoclonal protein ≥ 1 g/dL
- Urine protein monoclonal light chain ≥ 200 mg/24 hours by electrophoresis
- Measurable serum free light chains ≥ 10 mg/dL, kappa or lambda, AND κ/λ ratio is abnormal (if serum and urine are not measurable as defined above)
- Evaluable disease, defined as monoclonal bone marrow plasmacytosis ≥ 30%
PATIENT CHARACTERISTICS:
- ECOG performance status 0-3
- Life expectancy > 3 months
- ANC ≥ 1,500/mm³
- Bilirubin ≤ 2.0 mg/dL
- Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
- AST ≤ 3 times ULN
- Creatinine ≤ 3.0 mg/dL
- Platelet count ≥ 100,000/mm³
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use 2 effective methods of contraception, including ≥ 1 highly effective method, ≥ 4 weeks before and during study treatment
- No uncontrolled infection
- No peripheral neuropathy ≥ grade 2
- No serious medical condition, laboratory abnormality, or psychiatric illness that would preclude study compliance
- No other active malignancy except for nonmelanoma skin cancer or carcinoma in situ
- Prior malignancy allowed if treated with curative intent and is free of disease for a period appropriate for that cancer
- No known hypersensitivity to thalidomide
- No known HIV positivity
- No infectious hepatitis A, B or C
- No history of deep vein thrombosis or other medical condition requiring the use of warfarin
- Able to take daily prophylactic acetylsalicylic acid (81 or 325 mg)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 4 weeks since prior radiotherapy for treatment of multiple myeloma
- No prior lenalidomide
- No other concurrent anticancer agents or treatments
- No concurrent steroids except prednisone ≤ 20 mg/day (or the equivalent) for concurrent illness or adrenal replacement therapy
- No other concurrent investigational therapy or agent for treatment of multiple myeloma
- No concurrent warfarin
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Mayo Clinic in Florida
Jacksonville, Florida, 32224
Mayo Clinic
Rochester, Minnesota, 55905
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259-5499
About this study
Official title: Phase I/II Trial of Melphalan, Prednisone Plus Lenalidomide in Patients With Newly Diagnosed Multiple Myeloma Who Are Not Candidates for Stem Cell Transplant
RATIONALE: Drugs used in chemotherapy, such as melphalan, prednisone, and lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of melphalan and lenalidomide when given together with prednisone and to see how well they work in treating patients with newly diagnosed multiple myeloma.
Read the detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of melphalan and lenalidomide in combination with prednisone in patients with newly diagnosed multiple myeloma.
- Determine the response rate in patients treated with this regimen. Secondary
- Determine the toxicity of this regimen in these patients. OUTLINE: This is a dose-escalation study of melphalan and lenalidomide followed by a phase II study.
- Phase I: Patients receive oral melphalan and oral prednisone daily on days 1-4. Patients also receive oral lenalidomide daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of melphalan and lenalidomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive oral melphalan and oral lenalidomide as in phase I at the MTD. Patients also receive oral prednisone as in phase I. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months for 3 years.
- Being tested
- lenalidomide, melphalan, prednisone
- Keywords
- stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lenalidomideDrug
Phase I - dose escalating: 5mg level -1, 10mg level 0, 10mg level 1, 15mg level 2, 20mg level 3, 25mg level 4, orally days 1-21 every 28 days until progression
Phase II - 10 mg orally days 1-21 every 28 days until progression
melphalanDrug
Phase I - dose escalating: 5mg/m^2 dose level -1, 5 mg/m^2 dose level 0, 8 mg/m^2 dose level 1 - 4, daily x 4 orally days every 28 days until progression
Phase II - 5mg/m^2 orally days 1-4 every 28 days until progression
prednisoneDrug
60mg/m^2, orally days 1-4 every 28 days until progression
| Study group | Role | What they receive |
|---|---|---|
| Treatment (Lenalidomide, Melphalan, Prednisone) | Experimental | Intervention: Drug: lenalidomide Dose determined by Phase I treatment schedule. Taken orally days 1-21 every 28 days until progression
Intervention: Drug: melphalan Dose determined by Phase I treatment schedule. Taken orally days 1-4 every 28 days until progression
Intervention: Drug: prednisone 60mg/m^2, orally days 1-4 every 28 days until progression Receives: Drug: lenalidomide; Drug: melphalan; Drug: prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patients With Overall Confirmed Response
Response that was confirmed on 2 consecutive evaluations.>
- Complete Response (CR): Complete disappearance of M-protein from serum and urine on immunofixations, normalization of Free Light Chain (FLC) ratio and <=5% plasma cells in bone marrow>
- Very Good Partial Response (VGPR): >=90% reduction in serum M-spike, Urine M-spike <100mg per 24 hours>
- Partial Response (PR): >=50% reduction in serum M-spike, Urine M-spike >=90% reduction or < 200mg per 24 hours, or >=50% decrease in difference between involved and uninvolved FLC levels or 50% decrease in bone marrow plasma cells
Measured: Every cycle during treatment
Secondary outcomes (4)
Progression-free Survival
Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression was defined as any one or more of the following:
An increase of 25% from lowest confirmed response in:
- Serum M-component (absolute increase >= 0.5g/dl)
- Urine M-component (absolute increase >= 200mg/24hour
- Difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl
- Bone marrow plasma cell percentage (absolute increase of >=10%)
Measured: registration to progressive disease (up to 3 years)
Overall Survival (OS) at 3 Years
OS was defined as the time from registration to death due to any cause. Patients who were alive were censored at date of last follow-up. The overall survival at 3 years (a percentage) is reported below.
Measured: registration to death (up to 3 years)
Duration of Response (DOR)
Duration of response was calculated from documentation of first response to date of progression in the subset of patients who responded. Patients without progression were censored at the date of last tumor evaluation.
Measured: from first response to progression or death (up to 3 years)
Percentage of Participants With Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3)
The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
Measured: Every cycle during treatment up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2007 (estimated)
- Study startJun 2005
- Primary completionApr 2008
- Study completion5 Aug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple Myeloma and Plasma Cell NeoplasmStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Vivek Roy, MD, FACP, Study chair, Mayo ClinicPhilip R. Greipp, MD, Principal investigator, Mayo ClinicCraig B. Reeder, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00477750
- Sponsor's protocol ID
- CDR0000546642
- Other IDs
- P30CA015083, MC038A, 2387-04, RV-MM-PI-025
- Status last verified
- Oct 2015
- First submitted
- 23 May 2007
- Last updated
- 11 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of Melphalan, Prednisone Plus Lenalidomide in Patients With Newly Diagnosed Multiple Myeloma Who Are Not Candidates for Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT00477750
- Acronym / sponsor ID
- CDR0000546642
- Keywords
- stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2005
- Primary completion
- Apr 2008 (actual)
- Study completion
- 5 Aug 2013 (actual)
- First posted
- 24 May 2007 (estimated)
- Results
- Posted 13 Dec 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as melphalan, prednisone, and lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of melphalan and lenalidomide when given together with prednisone and to see how well they work in treating patients with newly diagnosed multiple myeloma.
Detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of melphalan and lenalidomide in combination with prednisone in patients with newly diagnosed multiple myeloma.
- Determine the response rate in patients treated with this regimen. Secondary
- Determine the toxicity of this regimen in these patients. OUTLINE: This is a dose-escalation study of melphalan and lenalidomide followed by a phase II study.
- Phase I: Patients receive oral melphalan and oral prednisone daily on days 1-4. Patients also receive oral lenalidomide daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of melphalan and lenalidomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive oral melphalan and oral lenalidomide as in phase I at the MTD. Patients also receive oral prednisone as in phase I. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months for 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (Lenalidomide, Melphalan, Prednisone) | Experimental | Drug: lenalidomide, Drug: melphalan, Drug: prednisoneIntervention: Drug: lenalidomide Dose determined by Phase I treatment schedule. Taken orally days 1-21 every 28 days until progression Intervention: Drug: melphalan Dose determined by Phase I treatment schedule. Taken orally days 1-4 every 28 days until progression Intervention: Drug: prednisone 60mg/m^2, orally days 1-4 every 28 days until progression |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lenalidomidePhase I - dose escalating: 5mg level -1, 10mg level 0, 10mg level 1, 15mg level 2, 20mg level 3, 25mg level 4, orally days 1-21 every 28 days until progression Phase II - 10 mg orally days 1-21 every 28 days until progression | Drug | Treatment (Lenalidomide, Melphalan, Prednisone) |
| melphalanPhase I - dose escalating: 5mg/m^2 dose level -1, 5 mg/m^2 dose level 0, 8 mg/m^2 dose level 1 - 4, daily x 4 orally days every 28 days until progression Phase II - 5mg/m^2 orally days 1-4 every 28 days until progression | Drug | Treatment (Lenalidomide, Melphalan, Prednisone) |
| prednisone60mg/m^2, orally days 1-4 every 28 days until progression | Drug | Treatment (Lenalidomide, Melphalan, Prednisone) |
Primary outcome
Patients With Overall Confirmed Response
Time frame: Every cycle during treatment
Response that was confirmed on 2 consecutive evaluations.> * Complete Response (CR): Complete disappearance of M-protein from serum and urine on immunofixations, normalization of Free Light Chain (FLC) ratio and <=5% plasma cells in bone marrow> * Very Good Partial Response (VGPR): >=90% reduction in serum M-spike, Urine M-spike <100mg per 24 hours> * Partial Response (PR): >=50% reduction in serum M-spike, Urine M-spike >=90% reduction or < 200mg per 24 hours, or >=50% decrease in difference between involved and uninvolved FLC levels or 50% decrease in bone marrow plasma cells
4 secondary outcomes
Progression-free Survival
Time frame: registration to progressive disease (up to 3 years)
Overall Survival (OS) at 3 Years
Time frame: registration to death (up to 3 years)
Duration of Response (DOR)
Time frame: from first response to progression or death (up to 3 years)
Percentage of Participants With Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3)
Time frame: Every cycle during treatment up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vivek Roy, MD, FACP study chair
Mayo Clinic
Philip R. Greipp, MD principal investigator
Mayo Clinic
Craig B. Reeder, MD principal investigator
Mayo Clinic
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing lenalidomide, melphalan and prednisone in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Mayo Clinic at 3 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?
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 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 13 Dec 2010). 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?
Patients With Overall Confirmed Response (time frame: Every cycle during treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Oct 2019.