MyelomaPhase 1/2NCT01079936
Lenalidomide and High-Dose Melphalan
A Phase 1/2 study testing Lenalidomide, Melphalan and Stem Cell Infusion in people with Myeloma and Stem Cell Transplantation, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find the highest tolerable dose of the combination of Revlimid (lenalidomide) and high-dose Alkeran (melphalan) that can be given to patients with multiple myeloma who will receive an autologous stem cell transplantation. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Myeloma, Stem Cell Transplantation
- What is being tested?
- Lenalidomide, Melphalan and Stem Cell Infusion
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to Mar 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with multiple myeloma with relapsed or progressive disease after achieving a partial or complete response to prior conventional therapy or autologous stem cell transplantation
- Age 18 to 80 years
- Performance score of at least 80% by Karnofsky or performance score of 0 or 1 (ECOG)
- Left ventricular ejection fraction =/> 40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
- FEV1, FVC and DLCO=/> 40%. No symptomatic pulmonary disease.
- Serum bilirubin <2 x upper limit of normal, SGPT <3x upper limit of normal. No evidence of chronic active hepatitis or cirrhosis. No pleural effusion or ascites > 1 L prior to drainage.
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- Creatinine Clearance =/> 50 ml/min
- HIV negative
- Negative beta HCG test in women with child bearing potential, defined as not post-menopausal for 24 months or no previous sterilization.
- Patients or guardian able to sign informed consent.
- All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
- Females of childbearing potential (FCBP) must have a negative serum pregnancy test with a sensitivity of at least 50 mIU/mL within 10 -14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and 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 4 weeks before she starts taking lenalidomide.
- Contd. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy. See Appendix F: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.
Who cannot join
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment.
- Patients with uncontrolled hypertension (systolic > 140, diastolic >90 despite anti-hypertensive therapy.)
- Patients with uncontrolled bacteria, viral or fungal infections (currently taking medication and progression of clinical symptoms).
- Known hypersensitivity or desquamating rash to either thalidomide or lenalidomide.
- Women who are pregnant (positive ß-HCG) or breastfeeding. (Lactating women must agree not to breast feed while taking lenalidomide and for 28 days after last dose of lenalidomide.)
- New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmia's, or electrocardiographic evidence of acute ischemia, or a 2nd or 3rd degree AV block or new left bundle branch block on EKG.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Study Of The Combination Of Lenalidomide With High-Dose Melphalan For Autologous Transplant in Patients With Multiple Myeloma
The goal of this clinical research study is to find the highest tolerable dose of the combination of Revlimid (lenalidomide) and high-dose Alkeran (melphalan) that can be given to patients with multiple myeloma who will receive an autologous stem cell transplantation. The safety of this combination therapy will also be studied.
Read the detailed description
The Study Drugs:
Melphalan is designed to damage the DNA (the genetic material of cells) of cells, which may cause cancer cells to die. High-dose melphalan is considered the standard of care for multiple myeloma.
Lenalidomide is designed to block a protein that plays a role in cell function and growth, which may cause cancer cells to die.
Study Dose Levels:
If you agree to take part in this study, you will be assigned to a dose level of lenalidomide based on when you join this study. Up to 4 dose levels of lenalidomide will be tested for safety. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen.
All participants will receive the same dose level of melphalan.
Once the highest tolerable dose of the combination of melphalan and lenalidomide is found, the next group of patients will be randomly assigned to 1 of 4 possible groups that will be determined by the computer, based on the safest and most effective dose level at that particular point.
Study Drug Administration:
You will take lenalidomide by mouth 1 time a day beginning 8 days before the stem cell transplant (Day -8). You will take the drug for 7 days (Days -8 through -2). You should take it with a few sips of water.
On Days -3 and -2, you will receive melphalan by vein over 30 minutes.
On Day 0, after you have received the chemotherapy study drugs, you will receive an infusion of stem cells, which were previously collected from you. This infusion of stem cells is given in an effort to help increase blood production and strengthen your immune system. You will receive antibiotics in an effort to decrease the likelihood that you will develop an infection.
Hospitalization following transplant usually lasts about 2-4 weeks, but may be longer. Some participants may be discharged earlier and followed in the outpatient clinic.
Study Visits:
About 1 month, 3 months, and 6 months after the transplant:
- You will have a physical exam and your medical history will be recorded.
- Blood (about 2 tablespoons) and urine will be collected for routine tests and to check the status of the disease.
- About 3 months after the transplant, you will have a bone marrow biopsy and aspiration to check the status of the disease. This will be repeated more often, if your doctor thinks it is needed.
About 1 year after the transplant:
- You will have a physical exam and your medical history will be recorded.
- Blood (about 2 tablespoons) and urine will be collected for routine tests.
- You will have a bone marrow biopsy and aspiration to check the status of the disease.
- You will have x-rays of your bones to check the status of the disease.
Length of Study:
Your participation in this study will be over after the 1 year transplant follow-up visit.
If intolerable side effects from the chemotherapy occur or there is sign of disease after the transplant, you will be taken off study. If you have intolerable side effects after you receive melphalan, then you will still have the transplant. However, if intolerable side effects develop before you take melphalan, you may be taken off study without having the transplant. If you are taken off study early, you still may need to return for routine post-transplant follow-up visits, if your transplant physician decides it is necessary.
It may be life-threatening to leave the study early during the conditioning regimen without following up with the stem cell transplant, because your blood cell counts may be dangerously low.
This is an investigational study. Lenalidomide and melphalan are commercially available and FDA approved for the treatment of myeloma. However, the use of lenalidomide with melphalan before an autologous stem cell transplant is investigational.
Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.
- Conditions
- Myeloma, Stem Cell Transplantation
- Being tested
- Lenalidomide, Melphalan, Stem Cell Infusion
- Keywords
- Multiple Myeloma, Lenalidomide, Revlimid, Melphalan, Alkeran, Autologous stem cell transplantation, High-dose chemotherapy
- Medical subject headings
- Neoplasms, Plasma Cell, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
Also called Revlimid, CC-5013
Beginning dose level 25 mg by mouth (PO) on Days -8 to -2
MelphalanDrug
Also called Alkeran
Dose level 100 mg/m2 by vein (IV) Days -3 and -2 over 30 minutes infusion
Stem Cell InfusionProcedure or surgery
Stem cell infusion on Day 0.
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide + High-Dose Melphalan | Experimental | Lenalidomide beginning dose level 25 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0. Receives: Drug: Lenalidomide; Drug: Melphalan; Procedure: Stem Cell Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Lenalidomide
There were 4 doses of lenalidomide in the dose escalation phase: 25 mg, 50 mg, 75 mg, and 100 mg. The first 12 patients were treated at these dose levels (3 patients per level) and safety assessed at each level. The MTD dose level was to be the level at which participants at each lenalidomide dose level had no dose limiting toxicity (DLT). DLT defined as as regimen-related death, graft failure, grade 3 or 4 atrial fibrillation, grade 4 deep venous thrombosis, or pulmonary embolism before day 30 after auto-HCT. Each participant received a fixed dose of Melphalan plus one of the four doses 25, 50, 75 or 100 mg of Lenalidomide orally for each of 7 days, -8 to -2 pre transplant.
Measured: Assessed at 21-28 Day Cycle
Number of Participants With Response (CR at Day 90)
Response is defined as the event that the participant is alive with complete response (CR) at day 90 (+/-30 days). CR defined as: A) Absence of monoclonal protein in urine and serum when analyzed by immunofixation electrophoresis. B) The bone marrow should be normal by morphological examination with <5% plasma cells. There should be < 1% aneuploid light chain restricted population by flow cytometry for DNA/cIg. C) While healing of bone lesions not required, no new lytic lesion should appear. Further compression fracture of spine will be not considered as progressive disease.
Measured: Day 90 after stem cell transplant
Number of Participants With Day 30 DLT (Overall Study, Phase I/Phase II)
Dose limiting toxicity (DLT) was defined as regimen-related death, graft failure, grade 3 or 4 atrial fibrillation, grade 4 deep venous thrombosis, or pulmonary embolism before day 30 after auto-HCT.
Measured: Day 30 following transplant
Participants With Grade 3 =/> Adverse Events
Number of participants experiencing adverse events above a Grade 3 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 2.
Measured: Day 90 after stem cell transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2010 (estimated)
- Study startMar 2010
- Primary completionMar 2015
- Study completionMar 2015
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 MyelomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Muzaffar H. Qazilbash, MD, Study chair, UT MD Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01079936
- Sponsor's protocol ID
- 2008-0661
- Other IDs
- NCI-2011-00561
- Status last verified
- May 2016
- First submitted
- 2 Mar 2010
- Last updated
- 6 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study Of The Combination Of Lenalidomide With High-Dose Melphalan For Autologous Transplant in Patients With Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01079936
- Acronym / sponsor ID
- 2008-0661
- Conditions
- Myeloma, Stem Cell Transplantation
- Keywords
- Multiple Myeloma, Lenalidomide, Revlimid, Melphalan, Alkeran, Autologous stem cell transplantation, High-dose chemotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Mar 2010
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 3 Mar 2010 (estimated)
- Results
- Posted 6 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to find the highest tolerable dose of the combination of Revlimid (lenalidomide) and high-dose Alkeran (melphalan) that can be given to patients with multiple myeloma who will receive an autologous stem cell transplantation. The safety of this combination therapy will also be studied.
Detailed description
The Study Drugs:
Melphalan is designed to damage the DNA (the genetic material of cells) of cells, which may cause cancer cells to die. High-dose melphalan is considered the standard of care for multiple myeloma.
Lenalidomide is designed to block a protein that plays a role in cell function and growth, which may cause cancer cells to die.
Study Dose Levels:
If you agree to take part in this study, you will be assigned to a dose level of lenalidomide based on when you join this study. Up to 4 dose levels of lenalidomide will be tested for safety. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen.
All participants will receive the same dose level of melphalan.
Once the highest tolerable dose of the combination of melphalan and lenalidomide is found, the next group of patients will be randomly assigned to 1 of 4 possible groups that will be determined by the computer, based on the safest and most effective dose level at that particular point.
Study Drug Administration:
You will take lenalidomide by mouth 1 time a day beginning 8 days before the stem cell transplant (Day -8). You will take the drug for 7 days (Days -8 through -2). You should take it with a few sips of water.
On Days -3 and -2, you will receive melphalan by vein over 30 minutes.
On Day 0, after you have received the chemotherapy study drugs, you will receive an infusion of stem cells, which were previously collected from you. This infusion of stem cells is given in an effort to help increase blood production and strengthen your immune system. You will receive antibiotics in an effort to decrease the likelihood that you will develop an infection.
Hospitalization following transplant usually lasts about 2-4 weeks, but may be longer. Some participants may be discharged earlier and followed in the outpatient clinic.
Study Visits:
About 1 month, 3 months, and 6 months after the transplant:
- You will have a physical exam and your medical history will be recorded.
- Blood (about 2 tablespoons) and urine will be collected for routine tests and to check the status of the disease.
- About 3 months after the transplant, you will have a bone marrow biopsy and aspiration to check the status of the disease. This will be repeated more often, if your doctor thinks it is needed.
About 1 year after the transplant:
- You will have a physical exam and your medical history will be recorded.
- Blood (about 2 tablespoons) and urine will be collected for routine tests.
- You will have a bone marrow biopsy and aspiration to check the status of the disease.
- You will have x-rays of your bones to check the status of the disease.
Length of Study:
Your participation in this study will be over after the 1 year transplant follow-up visit.
If intolerable side effects from the chemotherapy occur or there is sign of disease after the transplant, you will be taken off study. If you have intolerable side effects after you receive melphalan, then you will still have the transplant. However, if intolerable side effects develop before you take melphalan, you may be taken off study without having the transplant. If you are taken off study early, you still may need to return for routine post-transplant follow-up visits, if your transplant physician decides it is necessary.
It may be life-threatening to leave the study early during the conditioning regimen without following up with the stem cell transplant, because your blood cell counts may be dangerously low.
This is an investigational study. Lenalidomide and melphalan are commercially available and FDA approved for the treatment of myeloma. However, the use of lenalidomide with melphalan before an autologous stem cell transplant is investigational.
Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide + High-Dose Melphalan | Experimental | Drug: Lenalidomide, Drug: Melphalan, Procedure: Stem Cell InfusionLenalidomide beginning dose level 25 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients with multiple myeloma with relapsed or progressive disease after achieving a partial or complete response to prior conventional therapy or autologous stem cell transplantation
- Age 18 to 80 years
- Performance score of at least 80% by Karnofsky or performance score of 0 or 1 (ECOG)
- Left ventricular ejection fraction =/> 40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
- FEV1, FVC and DLCO=/> 40%. No symptomatic pulmonary disease.
Key exclusion criteria (6 listed)
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment.
- Patients with uncontrolled hypertension (systolic > 140, diastolic >90 despite anti-hypertensive therapy.)
- Patients with uncontrolled bacteria, viral or fungal infections (currently taking medication and progression of clinical symptoms).
- Known hypersensitivity or desquamating rash to either thalidomide or lenalidomide.
- Women who are pregnant (positive ß-HCG) or breastfeeding. (Lactating women must agree not to breast feed while taking lenalidomide and for 28 days after last dose of lenalidomide.)
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 |
|---|---|---|
| LenalidomideAlso: Revlimid, CC-5013Beginning dose level 25 mg by mouth (PO) on Days -8 to -2 | Drug | Lenalidomide + High-Dose Melphalan |
| MelphalanAlso: AlkeranDose level 100 mg/m2 by vein (IV) Days -3 and -2 over 30 minutes infusion | Drug | Lenalidomide + High-Dose Melphalan |
| Stem Cell InfusionStem cell infusion on Day 0. | Procedure or surgery | Lenalidomide + High-Dose Melphalan |
Primary outcome
Maximum Tolerated Dose (MTD) of Lenalidomide
Time frame: Assessed at 21-28 Day Cycle
There were 4 doses of lenalidomide in the dose escalation phase: 25 mg, 50 mg, 75 mg, and 100 mg. The first 12 patients were treated at these dose levels (3 patients per level) and safety assessed at each level. The MTD dose level was to be the level at which participants at each lenalidomide dose level had no dose limiting toxicity (DLT). DLT defined as as regimen-related death, graft failure, grade 3 or 4 atrial fibrillation, grade 4 deep venous thrombosis, or pulmonary embolism before day 30 after auto-HCT. Each participant received a fixed dose of Melphalan plus one of the four doses 25, 50, 75 or 100 mg of Lenalidomide orally for each of 7 days, -8 to -2 pre transplant.
Number of Participants With Response (CR at Day 90)
Time frame: Day 90 after stem cell transplant
Response is defined as the event that the participant is alive with complete response (CR) at day 90 (+/-30 days). CR defined as: A) Absence of monoclonal protein in urine and serum when analyzed by immunofixation electrophoresis. B) The bone marrow should be normal by morphological examination with <5% plasma cells. There should be < 1% aneuploid light chain restricted population by flow cytometry for DNA/cIg. C) While healing of bone lesions not required, no new lytic lesion should appear. Further compression fracture of spine will be not considered as progressive disease.
Number of Participants With Day 30 DLT (Overall Study, Phase I/Phase II)
Time frame: Day 30 following transplant
Dose limiting toxicity (DLT) was defined as regimen-related death, graft failure, grade 3 or 4 atrial fibrillation, grade 4 deep venous thrombosis, or pulmonary embolism before day 30 after auto-HCT.
Participants With Grade 3 =/> Adverse Events
Time frame: Day 90 after stem cell transplant
Number of participants experiencing adverse events above a Grade 3 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 2.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- UT MD Anderson Cancer CenterLink provided by the sponsor.
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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.
Muzaffar H. Qazilbash, MD study chair
UT MD Anderson Cancer Center
1 site 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 Stem Cell Infusion in people with Myeloma and Stem Cell Transplantation, run by M.D. Anderson Cancer Center at 1 site 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 13 inclusion and 6 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 6 Jun 2016. 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 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 6 Jun 2016). 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?
Maximum Tolerated Dose (MTD) of Lenalidomide (time frame: Assessed at 21-28 Day Cycle). The study lists 4 primary outcomes in all. 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 6 Jun 2016.