Multiple Myeloma
Conditions
Keywords
multiple myeloma, polysomnography, quality of life, exercise
Brief summary
The purpose of the study was to determine the effect of Epoetin alfa therapy (short term versus long term) with and without a home-based individualized exercise program that incorporated aerobic and strength resistance training for patients being treated with high-dose chemotherapy and autologous peripheral bloodstem cell transplantation (PBSC T) for multiple myeloma. The endpoints for the study included the number of attempts at and total number of days of stem cell collection, number of RBC and platelet transfusions during the transplantation period, time-to-recovery after transplantation, and response to intensive therapy for multiple myeloma.
Interventions
DRUGEpoetin Alfa
Epoetin alfa was administered per an IRB approved algorithm to study participants when hemoglobin levels dropped during high dose chemotherapy. The usual dose is 150 units/kg og body weight, three times per week, or 40,000 units weekly, with suggested target hemoglobin range of 10-12 g/dl.
BEHAVIORALExercise
A home-based individualized exercise program that incorporated aerobic and strength resistance training.
Standard PBSCT for multiple myeloma
BIOLOGICALRed Blood Cell Transfusion
RBC Transfusion was administered as needed
DRUGThalidomide
Fifty percent of the participants received 400 mg daily
Patients who received thalidomide also received prophylactic low molecular weight heparin
BIOLOGICALPlatelet Transfusion
Platelet transfusions were administered as needed
DRUGMelphalan
Administered with autologous peripheralblood stem cell transplantation (PBSCT) for multiple myeloma
DRUGTotal Therapy II
Standard Induction chemotherapy care included: vincristine, doxorubicin, and dexamethasone (VAD) (0.5 mg, 10 mg/m2, and 40 mg, respectively);dexamethasone, cyclophosphamide,etoposide, and cisplatin (DCEP) (40 mg, 400 mg/m2, 40 mg/m2, and 15 mg/m2,respectively); and cyclophosphamide,doxorubicin, and dexamethasone (CAD) (750 mg/m2, 15 mg/m2, and 40 mg, respectively) for mobilization.
Sponsors
National Institutes of Health (NIH)
Ortho Biotech Clinical Affairs, L.L.C.
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Those who were not at high risk for impending pathologic fracture or cord compression, as determined by magnetic resonance imaging and other radiology reports and physician assessments,and enrolled in Total Therapy treatment protocols were invited to participate in the study.
Exclusion criteria
Patients were excluded if they showed any of the following attributes/conditions: * Inability to understand the intent of the study * Current diagnosis with a major psychiatric illness * Presence of microcytic or macrocytic anemia * Uncontrolled hypertension * Red cell transfusions within 2 weeks; and * Recombinant epoetin alfa within 8 weeks of study enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Days of Stem Cell Collection (Long Term) | up to 30 weeks | — |
| Number of Stem Cell Collection Attempts (Long Term) | up to 30 weeks | — |
| Total Number of Days of Stem Cell Collection (Short Term) | up to 15 weeks | — |
| Number of Red Blood Cell Transfusions Needed to Maintain Hemoglobin Levels (Short Term) | up to 15 weeks | The targeted hemoglobin level for each participant was 10-12 g/dl. This is the number of red blood cell (RBC) transfusions administered to participants, as part of the investigational therapy algorithm, in an attempt to alleviate the anemia caused by multiple myeloma and high-dose chemotherapy. The numbers of RBC and platelet transfusions were obtained from the University of Arkansas for Medical Sciences blood bank. |
| Number of Red Blood Cell Transfusions Needed to Maintain Hemoglobin Levels (Long Term) | up to 30 weeks | The targeted hemoglobin level for each participant was 10-12 g/dl. This is the number of red blood cell (RBC) transfusions administered to participants, as part of the investigational therapy algorithm, in an attempt to alleviate the anemia caused by multiple myeloma and high-dose chemotherapy. The numbers of RBC and platelet transfusions were obtained from the University of Arkansas for Medical Sciences blood bank. |
| Number of Platelet Transfusions Needed to Maintain Adequate Number of Platelets.(Short Term) | up to 15 weeks | — |
| Number of Platelet Transfusions Needed to Maintain Adequate Number of Platelets. (Long Term) | up to 30 weeks | — |
| Number of Stem Cell Collection Attempts (Short Term) | up to 15 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Long Term) | up to 30 weeks | Hemoglobin Levels were measured at baseline, before peripheral blood stem cell transplantation (PBSCT), during PBSCT and at hospital discharge. |
| Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Short Term) | up to 15 weeks | Hemoglobin Levels were measured at baseline, before peripheral blood stem cell transplantation (PBSCT), During PBSCT and at hospital discharge. |
Countries
United States
Participant flow
Recruitment details
Study conducted at multiple myeloma international referral center included patients newly diagnosed & eligible for treatment with aggressive treatment. Protocol included tandem peripheral blood stem cell transplants.
Participants by arm
| Arm | Count |
|---|---|
| Usual Care Participants received standard care for multiple myeloma which included: For the Short term study: Total Therapy II Chemotherapy Regimen (See Protocol) and Stem Cell Harvest. For the Long term study: Total Therapy II Chemotherapy Regimen (See Protocol) and melphalan with autologous peripheral-blood stem cell transplantation (PBSCT). For both the short and long term studies, red blood cell (RBC) and platelet transfusions were administered as needed, in addition to Epoetic Alfa (EPO) when hemoglobin levels dropped during high dose chemotherapy. The usual EPO dose is 150 units/kg of body weight, three times per week, or 40,000 units weekly, with suggested target hemoglobin range of 10-12 g/dl. Study participants were asked to remain as active as possible but not prescribed an individualized exercise program. Participants were stratified by thalidomide administration and by age (\<=60 versus \>60).Participants who received thalidomide also received low-molecular weight heparin | 69 |
| Exercise Participants received standard care for multiple myeloma which included: For the Short term study: Total Therapy II Chemotherapy Regimen (See Protocol) and Stem Cell Harvest. For the Long term study: Total Therapy II Chemotherapy Regimen (See Protocol) and melphalan with autologous peripheral-blood stem cell transplantation (PBSCT). For both the short and long term studies, red blood cell (RBC) and platelet transfusions as needed, in addition to Epoetic Alfa (EPO) when hemoglobin levels dropped during high dose chemotherapy. The usual EPO dose is 150 units/kg of body weight, three times per week, or 40,000 units weekly, with suggested target hemoglobin range of 10-12 g/dl. Study participants were computer randomized to an individualized exercise program that incorporated aerobic and strength resistance training. Participants were stratified by thalidomide administration and by age (\<=60 versus \>60). Participants who received thalidomide also received low-molecular weight heparin. | 66 |
| Total | 135 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Short Term Participation | Death | 1 | 1 |
| Short Term Participation | Withdrawal by Subject | 3 | 5 |
| Short Term Participation | withdrew from multiple myeloma treatment | 3 | 2 |
Baseline characteristics
| Characteristic | Usual Care | Exercise | Total |
|---|---|---|---|
| Age, Continuous Long Term Participants | 54.4 years STANDARD_DEVIATION 9.7 | 55.4 years STANDARD_DEVIATION 11.4 | 55 years STANDARD_DEVIATION 10.6 |
| Age, Continuous Short Term Participants | 58 years STANDARD_DEVIATION 9.2 | 54.5 years STANDARD_DEVIATION 10.4 | 55 years STANDARD_DEVIATION 10 |
| Race/Ethnicity, Customized Caucasian (long term study) | 32 participants | 31 participants | 63 participants |
| Race/Ethnicity, Customized Caucasian (short term study) | 31 participants | 27 participants | 58 participants |
| Race/Ethnicity, Customized Other (long term study) | 2 participants | 4 participants | 6 participants |
| Race/Ethnicity, Customized Other (short term study) | 4 participants | 4 participants | 8 participants |
| Region of Enrollment United States | 69 participants | 66 participants | 135 participants |
| Sex/Gender, Customized Female (long term study) | 10 participants | 12 participants | 22 participants |
| Sex/Gender, Customized Female (short term study) | 22 participants | 19 participants | 41 participants |
| Sex/Gender, Customized Male (long term study) | 24 participants | 23 participants | 47 participants |
| Sex/Gender, Customized Male (short term study) | 13 participants | 12 participants | 25 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 17 / 62 | 25 / 58 |
Outcome results
Primary
Number of Platelet Transfusions Needed to Maintain Adequate Number of Platelets. (Long Term)
Time frame: up to 30 weeks
Population: For the exercise group 8 participants who entered the study were not included in the analysis (2 withdrew from myeloma treatment, 1 died, 5 withdrew from study). For the usual care group 7 were not included in the analysis (3 withdrew from myeloma treatment, 1 died, 3 withdrew from study).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Number of Platelet Transfusions Needed to Maintain Adequate Number of Platelets. (Long Term) | 3.6 Platelet Transfusions | Standard Deviation 4.5 |
| Exercise | Number of Platelet Transfusions Needed to Maintain Adequate Number of Platelets. (Long Term) | 2.0 Platelet Transfusions | Standard Deviation 2 |
Comparison: The null hypothesis was that there would be no difference between groups for the number of platelet transfusions.p-value: <0.025ANOVA
Primary
Number of Platelet Transfusions Needed to Maintain Adequate Number of Platelets.(Short Term)
Time frame: up to 15 weeks
Population: For the exercise group 8 participants who entered the study were not included in the analysis (2 withdrew from myeloma treatment, 1 died, 5 withdrew from study). For the usual care group 7 were not included in the analysis (3 withdrew from myeloma treatment, 1 died, 3 withdrew from study).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Number of Platelet Transfusions Needed to Maintain Adequate Number of Platelets.(Short Term) | 3.1 Platelet transfusions | Standard Deviation 3.2 |
| Exercise | Number of Platelet Transfusions Needed to Maintain Adequate Number of Platelets.(Short Term) | 2.3 Platelet transfusions | Standard Deviation 1.6 |
p-value: <0.025ANOVA
Primary
Number of Red Blood Cell Transfusions Needed to Maintain Hemoglobin Levels (Long Term)
The targeted hemoglobin level for each participant was 10-12 g/dl. This is the number of red blood cell (RBC) transfusions administered to participants, as part of the investigational therapy algorithm, in an attempt to alleviate the anemia caused by multiple myeloma and high-dose chemotherapy. The numbers of RBC and platelet transfusions were obtained from the University of Arkansas for Medical Sciences blood bank.
Time frame: up to 30 weeks
Population: For the exercise group 8 participants who entered the study were not included in the analysis (2 withdrew from myeloma treatment, 1 died, 5 withdrew from study). For the usual care group 7 were not included in the analysis (3 withdrew from myeloma treatment, 1 died, 3 withdrew from study).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Number of Red Blood Cell Transfusions Needed to Maintain Hemoglobin Levels (Long Term) | 1.8 RBC Transfusions | Standard Deviation 2.9 |
| Exercise | Number of Red Blood Cell Transfusions Needed to Maintain Hemoglobin Levels (Long Term) | 1.0 RBC Transfusions | Standard Deviation 1.3 |
Comparison: The null hypothesis is that there was no difference in the number of RBC tranfusions in the exercise versus usual care groups. Data was combined from the short and long term RBC transfusions.p-value: <0.025ANOVA
Primary
Number of Red Blood Cell Transfusions Needed to Maintain Hemoglobin Levels (Short Term)
The targeted hemoglobin level for each participant was 10-12 g/dl. This is the number of red blood cell (RBC) transfusions administered to participants, as part of the investigational therapy algorithm, in an attempt to alleviate the anemia caused by multiple myeloma and high-dose chemotherapy. The numbers of RBC and platelet transfusions were obtained from the University of Arkansas for Medical Sciences blood bank.
Time frame: up to 15 weeks
Population: For the exercise group 8 participants who entered the study were not included in the analysis (2 withdrew from myeloma treatment, 1 died, 5 withdrew from study). For the usual care group 7 were not included in the analysis (3 withdrew from myeloma treatment, 1 died, 3 withdrew from study).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Number of Red Blood Cell Transfusions Needed to Maintain Hemoglobin Levels (Short Term) | 2.3 RBC Transfusions | Standard Deviation 2.5 |
| Exercise | Number of Red Blood Cell Transfusions Needed to Maintain Hemoglobin Levels (Short Term) | 1.8 RBC Transfusions | Standard Deviation 2.2 |
Comparison: The null hypothesis was that there would be no difference between groups for the number of RBC transfusions.p-value: <0.025ANOVA
Primary
Number of Stem Cell Collection Attempts (Long Term)
Time frame: up to 30 weeks
Population: For the exercise group 8 participants who entered the study were not included in the analysis (2 withdrew from myeloma treatment, 1 died, 5 withdrew from study). For the usual care group 7 were not included in the analysis (3 withdrew from myeloma treatment, 1 died, 3 withdrew from study).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Number of Stem Cell Collection Attempts (Long Term) | 1.3 Stem Cell Collection Attempts | Standard Deviation 0.6 |
| Exercise | Number of Stem Cell Collection Attempts (Long Term) | 1.1 Stem Cell Collection Attempts | Standard Deviation 0.4 |
Comparison: The null hypothesis was that there would be no difference between groups for the number of stem cell collection attempts.p-value: <0.025ANOVA
Primary
Number of Stem Cell Collection Attempts (Short Term)
Time frame: up to 15 weeks
Population: For the exercise group 8 participants who entered the study were not included in the analysis (2 withdrew from myeloma treatment, 1 died, 5 withdrew from study). For the usual care group 7 were not included in the analysis (3 withdrew from myeloma treatment, 1 died, 3 withdrew from study).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Number of Stem Cell Collection Attempts (Short Term) | 1.4 Stem Cell Collection Attempts | Standard Deviation 0.8 |
| Exercise | Number of Stem Cell Collection Attempts (Short Term) | 1.1 Stem Cell Collection Attempts | Standard Deviation 0.3 |
p-value: <0.025ANOVA
Primary
Total Number of Days of Stem Cell Collection (Long Term)
Time frame: up to 30 weeks
Population: For the exercise group 8 participants who entered the study were not included in the analysis (2 withdrew from myeloma treatment, 1 died, 5 withdrew from study). For the usual care group 7 were not included in the analysis (3 withdrew from myeloma treatment, 1 died, 3 withdrew from study).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Total Number of Days of Stem Cell Collection (Long Term) | 4.9 Days | Standard Deviation 3.1 |
| Exercise | Total Number of Days of Stem Cell Collection (Long Term) | 4.5 Days | Standard Deviation 3.1 |
Comparison: The null hypothesis was that there would be no difference between groups for the number of days of stem cell collections.p-value: <0.025ANOVA
Primary
Total Number of Days of Stem Cell Collection (Short Term)
Time frame: up to 15 weeks
Population: For the exercise group 8 participants who entered the study were not included in the analysis (2 withdrew from myeloma treatment, 1 died, 5 withdrew from study). For the usual care group 7 were not included in the analysis (3 withdrew from myeloma treatment, 1 died, 3 withdrew from study).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care | Total Number of Days of Stem Cell Collection (Short Term) | 5.3 Days | Standard Deviation 4 |
| Exercise | Total Number of Days of Stem Cell Collection (Short Term) | 4.0 Days | Standard Deviation 2.3 |
Comparison: The null hypothesis was that there would be no difference between groups for the number of days of stem cell collections.p-value: <0.025ANOVA
Secondary
Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Long Term)
Hemoglobin Levels were measured at baseline, before peripheral blood stem cell transplantation (PBSCT), during PBSCT and at hospital discharge.
Time frame: up to 30 weeks
Population: For the exercise group 8 participants who entered the study were not included in the analysis (2 withdrew from myeloma treatment, 1 died, 5 withdrew from study). For the usual care group 7 were not included in the analysis (3 withdrew from myeloma treatment, 1 died, 3 withdrew from study).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Usual Care | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Long Term) | Baseline | 11.5 g/dl | Standard Deviation 1.8 |
| Usual Care | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Long Term) | Before Transplantation | 12.0 g/dl | Standard Deviation 1.6 |
| Usual Care | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Long Term) | During Transplanation | 10.8 g/dl | Standard Deviation 1.1 |
| Usual Care | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Long Term) | At Discharge | 10.9 g/dl | Standard Deviation 1.4 |
| Exercise | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Long Term) | At Discharge | 11.0 g/dl | Standard Deviation 1.3 |
| Exercise | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Long Term) | Baseline | 11.7 g/dl | Standard Deviation 1.8 |
| Exercise | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Long Term) | During Transplanation | 10.8 g/dl | Standard Deviation 1.1 |
| Exercise | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Long Term) | Before Transplantation | 12.0 g/dl | Standard Deviation 1.4 |
Secondary
Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Short Term)
Hemoglobin Levels were measured at baseline, before peripheral blood stem cell transplantation (PBSCT), During PBSCT and at hospital discharge.
Time frame: up to 15 weeks
Population: For the exercise group 8 participants who entered the study were not included in the analysis (2 withdrew from myeloma treatment, 1 died, 5 withdrew from study). For the usual care group 7 were not included in the analysis (3 withdrew from myeloma treatment, 1 died, 3 withdrew from study).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Usual Care | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Short Term) | Baseline | 12.1 g/dl | Standard Deviation 1.6 |
| Usual Care | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Short Term) | Before transplantation | 10.8 g/dl | Standard Deviation 1.5 |
| Usual Care | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Short Term) | During transplantation | 10.1 g/dl | Standard Deviation 0.7 |
| Usual Care | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Short Term) | At discharge | 10.6 g/dl | Standard Deviation 1.4 |
| Exercise | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Short Term) | At discharge | 10.6 g/dl | Standard Deviation 1.1 |
| Exercise | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Short Term) | Baseline | 11.6 g/dl | Standard Deviation 1.7 |
| Exercise | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Short Term) | During transplantation | 10.4 g/dl | Standard Deviation 0.9 |
| Exercise | Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Short Term) | Before transplantation | 11.0 g/dl | Standard Deviation 1.6 |
Comparison: The null hypothesis was that there would be no difference between groups for the number of platelet transfusions.p-value: <0.025ANOVA