Multiple Myeloma
Conditions
Keywords
CYCLOPHOSPHAMIDE (CYTOXAN), DEXAMETHASONE, G-CSF, Lenalidomide, MELPHALAN, PEG-FILGRASTIM (NEULASTA), 08-121
Brief summary
The purpose of this study is to compare the effects, good and bad, of two ways to treat patients with standard-risk symptomatic multiple myeloma. Patients with standard-risk myeloma have myeloma with specific features: levels of 2 blood tests have to be in a specific range and there can be no myeloma tumors found outside of the bones or bone marrow, the areas where myeloma is usually discovered. In past clinical studies, patients with standard-risk myeloma have done well with intensive therapy in the form of stem cell transplant. But multiple myeloma is not curable and, although it may respond to standard treatments including stem cell transplant, myeloma always recurs.
Interventions
PROCEDUREStem cell transplant x 1 or x 2
After 4 cycles of Ld, eligible patients will undergo stem cell mobilization and collection with standard-of-care cyclophosphamide and Neupogen (G-CSF) or with plerixafor G-CSF. Mobilization with cyclophosphamide is preferred, but plerixafor is also allowed. Ld will be held for at least 2 weeks prior to stem cell mobilization. On the SCT arm, patients not achieving VGPR by 3 months after the 1st SCT will undergo a 2nd SCT. All patients, after one or two SCT, will receive maintenance L.
Patients will then be randomized to continued Ld or high-dose melphalan with SCT. On the SCT arm patients not achieving VGPR by 3 months after the 1st SCT will undergo a 2nd SCT. All patients after one or two SCT, will receive maintenance L.
Sponsors
Tufts Medical Center
Lahey Clinic
Memorial Sloan Kettering Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 and ≤ 75 * Histologic and serologic findings from MSKCC confirming the diagnosis of multiple myeloma. Standard diagnostic criteria for multiple myeloma will be used, as per the revised International Myeloma Working Group diagnostic criteria. * Patients must have symptomatic multiple myeloma without advanced organ damage (such as multiple fractures or advanced bone disease causing immobilization, renal failure, spinal cord compression, or organ compromise due to soft tissue plasmacytoma). If immediate therapy with radiation and high-dose steroids (eg, for cord compression) or with bortezomib-based therapy (eg, for renal failure) is required, the patient is not eligible for this trial. * Patients may have received 1 cycle of prior therapy with dexamethasone for multiple myeloma. * Adequate organ function is required, defined as follows: * ANC ≥ 1,500/μl and platelets ≥ 100,000/μl (unless low ANC and platelets are due to multiple myeloma) * Serum bilirubin ≤ 2.0 mg/dl * AST, ALT and alkaline phosphatase \< 3 times the upper limit of laboratory normal * Adequate renal function as assessed by calculated creatinine using Cockcroft-Gault estimation of CrCl (see Appendix I): Subjects must have calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula * Performance status (ECOG) ≤ 2 (Appendix E). * Eligible for SCT with LVEF ≥ 50% by MUGA or ECHO, and diffusing capacity \> 50% predicted by pulmonary function testing * Ability to understand the investigational nature of this study and to give informed consent * All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements the of Revlimid REMS® program * 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 prior to prescribing lenalidomide for cycle 1 (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 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree not to father a child and 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 C: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods. * Able to take aspirin 325mg or 81mg daily as prophylactic anticoagulation (patients intolerant to ASA may use Coumadin or low molecular weight heparin).
Exclusion criteria
* Prior treatment for myeloma except for one cycle of dexamethasone * History of thromboembolic disease within the past 6 months regardless of anticoagulation * Myocardial infarction within 6 months prior to enrollment, or New York Hospital Association (NYHA) Class III or IV heart failure (see APPENDIX F), uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities. * Pregnant or breast-feeding women are excluded due to the potential teratogenicity of lenalidomide. * Concurrent active malignancy other than non-melanoma skin cancers or carcinoma-insitu of the cervix, or presence of myelodysplastic or myeloproliferative disease. Patients with prior malignancies with a disease-free interval of ≥ 5 years are eligible. * Patients who have had prior malignancies within the past 5 years but are considered to be cured with a low likelihood of recurrence may be eligible at the discretion of the Principal Investigator. * Active hepatitis B or C infection * HIV 1 or 2 positivity * Any other medical condition or laboratory evaluation that, in the treating physician's or principal investigator's opinion, makes the patient unsuitable to participate in this clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival (PFS) Rate at 2 Years After Enrollment in Untreated Patients With Multiple Myeloma. | 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With VGPR + CR Rate | 2 years | VGPR/Very Good Partial Response + CR/Complete Response (\>/= VGPR) for each study arm Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR |
| Overall Response Rates | 2 years | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR |
| Overall Survival | up to 4 years | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Continue Lenalidomide and Dexamethasone All patients on this study start with the same treatment, lenalidomide and dexamethasone by mouth. After patients have received 4 cycles of lenalidomide and dexamethasone and are within 2 weeks of completing stem cell collection, they are randomized (like the toss of a coin) to either :
stem cell transplant right after collection
* continue lenalidomide and dexamethasone
* saving stem cell transplant for a later time.
lenalidomide and dexamethasone: Patients will then be randomized to continued Ld or high-dose melphalan with SCT. On the SCT arm patients not achieving VGPR by 3 months after the 1st SCT will undergo a 2nd SCT. All patients after one or two SCT, will receive maintenance L. | 26 |
| Stem Cell Transplant x 1 or x 2 All patients on this study start with the same treatment, lenalidomide and dexamethasone by mouth. After patients have received 4 cycles of lenalidomide and dexamethasone and are within 2 weeks of completing stem cell collection, they are randomized (like the toss of a coin) to either :
* stem cell transplant right after collection
* continue lenalidomide and dexamethasone, saving stem cell transplant for a later time.
Stem cell transplant x 1 or x 2: After 4 cycles of Ld, eligible patients will undergo stem cell mobilization and collection with standard-of-care cyclophosphamide and Neupogen (G-CSF) or with plerixafor G-CSF. Mobilization with cyclophosphamide is preferred, but plerixafor is also allowed. Ld will be held for at least 2 weeks prior to stem cell mobilization.
On the SCT arm, patients not achieving VGPR by 3 months after the 1st SCT will undergo a 2nd SCT. All patients, after one or two SCT, will receive maintenance L. | 24 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 5 |
| Overall Study | Inadequate response to induction | 0 | 0 | 9 |
| Overall Study | Not treated on protocol study | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Continue Lenalidomide and Dexamethasone | Total | Stem Cell Transplant x 1 or x 2 |
|---|---|---|---|
| Age, Continuous | 61.3 years | 60.96 years | 60.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 9 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 39 Participants | 20 Participants |
| Region of Enrollment United States | 26 Participants | 50 Participants | 24 Participants |
| Sex: Female, Male Female | 13 Participants | 21 Participants | 8 Participants |
| Sex: Female, Male Male | 13 Participants | 29 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 26 | 5 / 24 |
| other Total, other adverse events | 26 / 26 | 24 / 24 |
| serious Total, serious adverse events | 17 / 26 | 18 / 24 |
Outcome results
Primary
Progression Free Survival (PFS) Rate at 2 Years After Enrollment in Untreated Patients With Multiple Myeloma.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continue Lenalidomide and Dexamethasone | Progression Free Survival (PFS) Rate at 2 Years After Enrollment in Untreated Patients With Multiple Myeloma. | 84.6 percentage of participants |
| Stem Cell Transplant x 1 or x 2 | Progression Free Survival (PFS) Rate at 2 Years After Enrollment in Untreated Patients With Multiple Myeloma. | 83.3 percentage of participants |
Secondary
Number of Participants With VGPR + CR Rate
VGPR/Very Good Partial Response + CR/Complete Response (\>/= VGPR) for each study arm Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Continue Lenalidomide and Dexamethasone | Number of Participants With VGPR + CR Rate | >/= VGPR | 18 Participants |
| Continue Lenalidomide and Dexamethasone | Number of Participants With VGPR + CR Rate | <VGPR | 8 Participants |
| Stem Cell Transplant x 1 or x 2 | Number of Participants With VGPR + CR Rate | >/= VGPR | 21 Participants |
| Stem Cell Transplant x 1 or x 2 | Number of Participants With VGPR + CR Rate | <VGPR | 3 Participants |
Secondary
Overall Response Rates
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Continue Lenalidomide and Dexamethasone | Overall Response Rates | Stringent Complete Response | 12 Participants |
| Continue Lenalidomide and Dexamethasone | Overall Response Rates | Very Good Partial Response | 6 Participants |
| Continue Lenalidomide and Dexamethasone | Overall Response Rates | Partial Response | 8 Participants |
| Continue Lenalidomide and Dexamethasone | Overall Response Rates | Complete Response | 0 Participants |
| Stem Cell Transplant x 1 or x 2 | Overall Response Rates | Complete Response | 2 Participants |
| Stem Cell Transplant x 1 or x 2 | Overall Response Rates | Stringent Complete Response | 12 Participants |
| Stem Cell Transplant x 1 or x 2 | Overall Response Rates | Partial Response | 3 Participants |
| Stem Cell Transplant x 1 or x 2 | Overall Response Rates | Very Good Partial Response | 7 Participants |
Secondary
Overall Survival
Time frame: up to 4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continue Lenalidomide and Dexamethasone | Overall Survival | 95.7 percentage of participants alive |
| Stem Cell Transplant x 1 or x 2 | Overall Survival | 90.6 percentage of participants alive |