Multiple Myeloma
Conditions
Keywords
Multiple myeloma, Newly diagnosed multiple myeloma, Thalidomide, Dexamethasone, DOXIL, Pegylated liposomal hydrochloride doxorubicin injection
Brief summary
The purpose of this study is to determine if Thalidomide + Dexamethasone or DOXIL (doxorubicin HCl liposome injection) + Thalidomide + Dexamethasone is more effective in treating newly diagnosed patients with multiple myeloma. The number of patients whose multiple myeloma disappears for a period of time (complete Response) will be studied to make the determination of which treatment is more effective.
Detailed description
This is a multi-center, open-label (all people know the identity of the intervention), randomized (the study medication is assigned by chance) study to compare the safety and effectiveness of Thalidomide + Dexamethasone versus DOXIL (doxorubicin HCl liposome injection) + Thalidomide + Dexamethasone in patients with newly diagnosed multiple myeloma. Treatments are administered in 28-day cycles. Patients will receive 4 to 12 treatment cycles, depending on the response of their multiple myeloma to the treatment (measured according to the European Group for Blood and Marrow Transplant Response Criteria). Patients will have additional tests that include Multiple Gated Acquisition (MUGA) scans or echocardiograms to assess the patients for potential cardiotoxicity that could be related to treatment with DOXIL (doxorubicin HCl liposome injection). Maximum duration of study participation for each participant will be 48 weeks.
Interventions
DRUGThalidomide
Participants will receive thalidomide orally every night (at bedtime) without food on days 1-28 and dosing will gradually increase during Cycle 1 starting at 50 mg on 1 to 7 days, 100 mg on 8 to 14 days, 150 mg on 15 to 21 days, and 200 mg 22 to 28 days. Thalidomide 200 mg per day will be administered for subsequent cycles. Participants will receive thalidomide for minimum of 4 cycles and a maximum of 12 cycles.
DRUGDexamethasone
Participants will receive dexamethasone 40 mg orally on Days 1 to 4, 9 to 12 and 17 to 20.
DRUGDOXIL
DOXIL 40 mg/m2 will be administered iintravenously (into a vein) on Day 1.
Sponsors
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Previously untreated, histologically confirmed multiple myeloma (per International Myeloma Working Group \[IMWG\] criteria * Eastern Cooperative Oncology Group (ECOG) status 0-2 * Adequate absolute neutrophil count (ANC), platelet count and hemoglobin * Adequate serum calcium * Enrollment in System for Thalidomide Education and Prescribing Safety Program (S.T.E.P.S.)
Exclusion criteria
* No treatment with dexamethasone for multiple myeloma * No peripheral neuropathy of Grade 2 or higher * No Left Ventricular Ejection Fraction (LVEF) of less than 45 percentage * No history of life-threatening thromboembolic events of any kind (ie, myocardial infarction, pulmonary embolism, stroke or others), within 1 year before enrollment in the study * No deep vein thrombosis (DVT) within 1 year of enrollment * No current anticoagulation for DVT
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate: Number of Participants Who Achieved a Complete Response | From Cycle 2 until 28 days following completion of treatment | Complete response rate to study medication is defined as number of participants who acheived complete response by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + plus no increase in size or number of lytic bone lesions. Complete response was assessed at the beginning of every treatment cycle prior to treatment, starting at Cycle 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to 1st Response | From Cycle 2 until 28 days following completion of treatment | Time to first response was defined as the interval from date of randomization to date of achieving a partial response (PR) or better according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein. |
| Time to Progression | From randomization until death or as assessed up to 2 years post last participant last treatment visit | Time to progression is the interval between the date of randomization until disease progression or death due to progression. |
| Overall Response: Number of Participants Who Achieved a Complete Response (CR) or Partial Response (PR) | From Cycle 2 until 28 days following completion of treatment | Overall response to study medication is defined as number of participants who acheived a complete response (CR) or partial response (PR) by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + plus no increase in size or number of lytic bone lesions; and PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein. |
| Transplantation: Number of Participants Who Underwent Transplantation (Peripheral Stem Cell / Bone Marrow) | From randomization until death or as assessed up to 2 years post last participant last treatment visit | — |
| Engraftment: Number of Participants Who Underwent Engraftment | From randomization until death or as assessed up to 2 years post last participant last treatment visit | Engraftment is the process of transplanted stem cells reproducing new cells. |
| Overall Survival: Number of Participants Died Due to Any Cause | From randomization until death or as assessed up to 2 years post last participant last treatment visit | — |
Countries
United States
Participant flow
Pre-assignment details
A total of 225 participants were randomnly assigned to treatment, 113 participants to the thal/dex group and 112 participants to the DOXIL/thal/dex group.
Participants by arm
| Arm | Count |
|---|---|
| Thalidomide + Dexamethasone Participants received thalidomide every night (at bedtime) without food on Days 1 to 28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20. | 113 |
| DOXIL + Thalidomide + Dexamethasone DOXIL 40 mg/m2 was administered intravenously on Day 1 and thalidomide every night (at bedtime) without food on Days 1-28 and dosing was gradually increased during Cycle 1 starting at 50 mg on Days 1 to 7, 100 mg on Days 8 to 14, 150 mg on 15 to 21, and 200 mg on Days 22 to 28. Thalidomide 200 mg per day was administered for subsequent cycles. Dexamethasone 40 mg was administered by mouth on Days 1 to 4, 9 to 12 and 17 to 20. | 112 |
| Total | 225 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 31 | 44 |
| Overall Study | Death | 2 | 4 |
| Overall Study | Disease Progression | 8 | 2 |
| Overall Study | Other | 19 | 13 |
| Overall Study | Physician Decision | 7 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Transplant planned | 28 | 27 |
| Overall Study | Withdrawal by Subject | 10 | 8 |
Baseline characteristics
| Characteristic | Thalidomide + Dexamethasone | DOXIL + Thalidomide + Dexamethasone | Total |
|---|---|---|---|
| Age, Continuous | 60.29 years STANDARD_DEVIATION 10.31 | 60.62 years STANDARD_DEVIATION 10.79 | 60.45 years STANDARD_DEVIATION 10.53 |
| Sex: Female, Male Female | 51 Participants | 44 Participants | 95 Participants |
| Sex: Female, Male Male | 62 Participants | 68 Participants | 130 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 110 / 110 | 104 / 106 |
| serious Total, serious adverse events | 48 / 110 | 53 / 106 |
Outcome results
Primary
Complete Response Rate: Number of Participants Who Achieved a Complete Response
Complete response rate to study medication is defined as number of participants who acheived complete response by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + plus no increase in size or number of lytic bone lesions. Complete response was assessed at the beginning of every treatment cycle prior to treatment, starting at Cycle 2.
Time frame: From Cycle 2 until 28 days following completion of treatment
Population: Intent-to-treat: Participants who were randomized to receive the treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thalidomide + Dexamethasone | Complete Response Rate: Number of Participants Who Achieved a Complete Response | 5 Participants |
| DOXIL + Thalidomide + Dexamethasone | Complete Response Rate: Number of Participants Who Achieved a Complete Response | 8 Participants |
p-value: 0.49Cochran-Mantel-Haenszel
Secondary
Engraftment: Number of Participants Who Underwent Engraftment
Engraftment is the process of transplanted stem cells reproducing new cells.
Time frame: From randomization until death or as assessed up to 2 years post last participant last treatment visit
Population: Intent-to-treat: Participants who were randomized to receive the treatment and who underwent transplantation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thalidomide + Dexamethasone | Engraftment: Number of Participants Who Underwent Engraftment | 25 Participants |
| DOXIL + Thalidomide + Dexamethasone | Engraftment: Number of Participants Who Underwent Engraftment | 25 Participants |
Secondary
Overall Response: Number of Participants Who Achieved a Complete Response (CR) or Partial Response (PR)
Overall response to study medication is defined as number of participants who acheived a complete response (CR) or partial response (PR) by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + plus no increase in size or number of lytic bone lesions; and PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein.
Time frame: From Cycle 2 until 28 days following completion of treatment
Population: Intent-to-treat: Participants who were randomized to receive the treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thalidomide + Dexamethasone | Overall Response: Number of Participants Who Achieved a Complete Response (CR) or Partial Response (PR) | 81 Participants |
| DOXIL + Thalidomide + Dexamethasone | Overall Response: Number of Participants Who Achieved a Complete Response (CR) or Partial Response (PR) | 76 Participants |
p-value: 0.42Cochran-Mantel-Haenszel
Secondary
Overall Survival: Number of Participants Died Due to Any Cause
Time frame: From randomization until death or as assessed up to 2 years post last participant last treatment visit
Population: Intent-to-treat: Participants who were randomized to receive the treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thalidomide + Dexamethasone | Overall Survival: Number of Participants Died Due to Any Cause | 21 Participants |
| DOXIL + Thalidomide + Dexamethasone | Overall Survival: Number of Participants Died Due to Any Cause | 22 Participants |
p-value: 0.9395% CI: [0.529, 1.797]Log Rank
Secondary
Time to 1st Response
Time to first response was defined as the interval from date of randomization to date of achieving a partial response (PR) or better according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein.
Time frame: From Cycle 2 until 28 days following completion of treatment
Population: Intent-to-treat: Participants who were randomized to receive the treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Thalidomide + Dexamethasone | Time to 1st Response | 44 Days |
| DOXIL + Thalidomide + Dexamethasone | Time to 1st Response | 58 Days |
p-value: 0.42Log Rank
Secondary
Time to Progression
Time to progression is the interval between the date of randomization until disease progression or death due to progression.
Time frame: From randomization until death or as assessed up to 2 years post last participant last treatment visit
Population: Intent-to-treat: Participants who were randomized to receive the treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Thalidomide + Dexamethasone | Time to Progression | 584 Days |
| DOXIL + Thalidomide + Dexamethasone | Time to Progression | 408 Days |
p-value: 0.5162Log Rank
Secondary
Transplantation: Number of Participants Who Underwent Transplantation (Peripheral Stem Cell / Bone Marrow)
Time frame: From randomization until death or as assessed up to 2 years post last participant last treatment visit
Population: Intent-to-treat: Participants who were randomized to receive the treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thalidomide + Dexamethasone | Transplantation: Number of Participants Who Underwent Transplantation (Peripheral Stem Cell / Bone Marrow) | 30 Participants |
| DOXIL + Thalidomide + Dexamethasone | Transplantation: Number of Participants Who Underwent Transplantation (Peripheral Stem Cell / Bone Marrow) | 28 Participants |