Effects of Exercise in Combination With Epoetin Alfa

• Sponsor: University of Arkansas (Other)
• Overall Status: Completed
• CT.gov ID: NCT00577096
• Collaborator: National Institutes of Health (NIH) (NIH), Ortho Biotech Clinical Affairs, L.L.C. (Industry)
• Enrollment: 120
• Location: 1
• Arms: 2
• Duration (Months): 32
• Patients Per Site Per Month: 3.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Epoetin Alfa; Behavioral: Exercise; Biological: Autologous Peripheral Blood Stem Cell Transplantation; Biological: Red Blood Cell Transfusion; Drug: Thalidomide; Drug: Heparin, Low-Molecular-Weight; Biological: Platelet Transfusion; Drug: Melphalan; Drug: Epoetin Alfa; Drug: Total Therapy II; Biological: Red Blood Cell Transfusion; Drug: Thalidomide; Drug: Heparin, Low-Molecular-Weight; Biological: Platelet Transfusion; Drug: Melphalan	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Effects of Exercise in Combination With Epoetin Alfa During High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma
• Study Start Date: Oct 1, 2001
• Actual Primary Completion Date: Jun 1, 2004
• Actual Study Completion Date: Jun 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exercise Study participants were computer randomized to an individualized exercise program. Participants were stratified within Arm according to whether or not they received thalidomide with heparin, and by age (60 and younger versus older than 60)	Drug: Epoetin 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.; Other Names: EPO ; Behavioral: Exercise; A home-based individualized exercise program that incorporated aerobic and strength resistance training.; Biological: Autologous Peripheral Blood Stem Cell Transplantation; Standard PBSCT for multiple myeloma; Other Names: (PBSCT) ; Biological: Red Blood Cell Transfusion; RBC Transfusion was administered as needed; Other Names: (RBC) ; Drug: Thalidomide; Fifty percent of the participants received 400 mg daily; Drug: Heparin, Low-Molecular-Weight; Patients who received thalidomide also received prophylactic low molecular weight heparin; Biological: Platelet Transfusion; Platelet transfusions were administered as needed; Drug: Melphalan; Administered with autologous peripheralblood stem cell transplantation (PBSCT) for multiple myeloma
Active Comparator: usual care Study participants were asked to remain as active as possible but not prescribed an individualized exercise program. Participants were stratified within Arm according to whether or not they received thalidomide with heparin, and by age (60 and younger versus older than 60)	Drug: Epoetin 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 of body weight, three times per week, or 40,000 units weekly, with suggested target hemoglobin range of 10-12 g/dl; Other Names: EPO ; Drug: Total 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.; Other Names: vincristine doxorubicin dexamethasone cyclophosphamide etoposide cisplatin ; Biological: Red Blood Cell Transfusion; RBC Transfusion was administered as needed; Other Names: RBC ; Drug: Thalidomide; Fifty percent of participants received 400 mg daily; Drug: Heparin, Low-Molecular-Weight; Patients who received thalidomide also received prophylactic low molecular weight heparin; Biological: Platelet Transfusion; Platelet transfusions were administered as needed; Drug: Melphalan; Administered with autologous peripheralblood stem cell transplantation (PBSCT) for multiple myeloma

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. Number of Platelet Transfusions Needed to Maintain Adequate Number of Platelets.(Short Term) [up to 15 weeks]

4. Number of Platelet Transfusions Needed to Maintain Adequate Number of Platelets. (Long Term) [up to 30 weeks]

5. Number of Stem Cell Collection Attempts (Short Term) [up to 15 weeks]

6. Number of Stem Cell Collection Attempts (Long Term) [up to 30 weeks]

7. Total Number of Days of Stem Cell Collection (Short Term) [up to 15 weeks]

8. Total Number of Days of Stem Cell Collection (Long Term) [up to 30 weeks]

Secondary Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205

Sponsors and Collaborators

• University of Arkansas
• National Institutes of Health (NIH)
• Ortho Biotech Clinical Affairs, L.L.C.

Investigators

• Study Director: Sharon K Coon, University of Oklahoma

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00577096
• Other Study ID Numbers: IRB # 29287; R01NR008937; Ortho Biotech Clinical Affairs
• First Posted: Dec 19, 2007
• Last Update Posted: Apr 6, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by , ,: multiple myeloma; polysomnography; quality of life; exercise
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Thalidomide; Dexamethasone; Cyclophosphamide; Melphalan; Cisplatin; Doxorubicin; Etoposide; Vincristine; Heparin; Calcium heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; Epoetin Alfa

Study Results

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.

Arm/Group Title	Usual Care	Exercise
Arm/Group Description	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	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.
Period Title: Short Term Participation
STARTED	69	66
COMPLETED	62	58
NOT COMPLETED	7	8
Period Title: Short Term Participation
STARTED	34	35
COMPLETED	34	35
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Usual Care	Exercise	Total
Arm/Group Description	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	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.	Total of all reporting groups
Overall Participants	69	66	135
Age (years) [Mean (Standard Deviation) ]
Short Term Participants	58 (9.2)	54.5 (10.4)	55 (10)
Long Term Participants	54.4 (9.7)	55.4 (11.4)	55 (10.6)
Sex/Gender, Customized (participants) [Number]
Male (short term study)	13 18.8%	12 18.2%	25 18.5%
Female (short term study)	22 31.9%	19 28.8%	41 30.4%
Male (long term study)	24 34.8%	23 34.8%	47 34.8%
Female (long term study)	10 14.5%	12 18.2%	22 16.3%
Race/Ethnicity, Customized (participants) [Number]
Caucasian (short term study)	31 44.9%	27 40.9%	58 43%
Other (short term study)	4 5.8%	4 6.1%	8 5.9%
Caucasian (long term study)	32 46.4%	31 47%	63 46.7%
Other (long term study)	2 2.9%	4 6.1%	6 4.4%
Region of Enrollment (participants) [Number]
United States	69 100%	66 100%	135 100%

Outcome Measures

1. Primary Outcome

Title	Number of Red Blood Cell Transfusions Needed to Maintain Hemoglobin Levels (Short Term)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Usual Care	Exercise
Arm/Group Description	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	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.
Measure Participants	28	23
Mean (Standard Deviation) [RBC Transfusions]	2.3 (2.5)	1.8 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Exercise
	Comments	The null hypothesis was that there would be no difference between groups for the number of RBC transfusions.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	ANOVA
Statistical Test of Hypothesis	p-Value	<0.025
	Comments	Bonferroni adjusted p-value for multiple comparisons.
	Method	ANOVA
	Comments	This is minus 9 (4 exercise, 5 usual care) participants who were unresponsive to Epoetin Alfa and included participants in short and long study.

2. Primary Outcome

Title	Number of Red Blood Cell Transfusions Needed to Maintain Hemoglobin Levels (Long Term)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Usual Care	Exercise
Arm/Group Description	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	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.
Measure Participants	34	35
Mean (Standard Deviation) [RBC Transfusions]	1.8 (2.9)	1.0 (1.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Exercise
	Comments	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.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	ANOVA
Statistical Test of Hypothesis	p-Value	<0.025
	Comments	Bonferroni adjusted p-value for multiple comparisons.
	Method	ANOVA
	Comments	This is minus 9 (4 exercise, 5 usual care) participants who were unresponsive to Epoetin Alfa and included participants in short and long study.

3. Primary Outcome

Title	Number of Platelet Transfusions Needed to Maintain Adequate Number of Platelets.(Short Term)
Time Frame	up to 15 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Usual Care	Exercise
Arm/Group Description	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	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.
Measure Participants	28	23
Mean (Standard Deviation) [Platelet transfusions]	3.1 (3.2)	2.3 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Exercise
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	T-test and chi-squared test to check for equivalence of groups for age, race and gender.
Statistical Test of Hypothesis	p-Value	<0.025
	Comments	Bonferroni adjusted p-value for multiple comparisons.
	Method	ANOVA
	Comments	Analysis included short and long term participants.

4. Primary Outcome

Title	Number of Platelet Transfusions Needed to Maintain Adequate Number of Platelets. (Long Term)
Time Frame	up to 30 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Usual Care	Exercise
Arm/Group Description	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	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.
Measure Participants	34	35
Mean (Standard Deviation) [Platelet Transfusions]	3.6 (4.5)	2.0 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Exercise
	Comments	The null hypothesis was that there would be no difference between groups for the number of platelet transfusions.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	T-test and chi-squared to check for equivalence of groups for age, race and gender.
Statistical Test of Hypothesis	p-Value	<0.025
	Comments	Bonferroni adjusted p-value for multiple comparisons.
	Method	ANOVA
	Comments	This is minus 9 (4 exercise, 5 usual care) participants who were unresponsive to Epoetin Alfa and included participants in short and long study.

5. Primary Outcome

Title	Number of Stem Cell Collection Attempts (Short Term)
Time Frame	up to 15 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Usual Care	Exercise
Arm/Group Description	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	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.
Measure Participants	28	23
Mean (Standard Deviation) [Stem Cell Collection Attempts]	1.4 (0.8)	1.1 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Exercise
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	ANOVA
Statistical Test of Hypothesis	p-Value	<0.025
	Comments	Bonferroni adjusted p-value for multiple comparisons.
	Method	ANOVA
	Comments	This is minus 9 (4 exercise, 5 usual care) participants who were unresponsive to Epoetin Alfa and included participants in short and long study.

6. Primary Outcome

Title	Number of Stem Cell Collection Attempts (Long Term)
Time Frame	up to 30 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Usual Care	Exercise
Arm/Group Description	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	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.
Measure Participants	34	35
Mean (Standard Deviation) [Stem Cell Collection Attempts]	1.3 (0.6)	1.1 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Exercise
	Comments	The null hypothesis was that there would be no difference between groups for the number of stem cell collection attempts.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	ANOVA
Statistical Test of Hypothesis	p-Value	<0.025
	Comments	Bonferroni adjusted p-value for multiple comparisons.
	Method	ANOVA
	Comments	This is minus 9 (4 exercise, 5 usual care) participants who were unresponsive to Epoetin Alfa and included participants in short and long study.

7. Primary Outcome

Title	Total Number of Days of Stem Cell Collection (Short Term)
Time Frame	up to 15 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Usual Care	Exercise
Arm/Group Description	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	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.
Measure Participants	28	23
Mean (Standard Deviation) [Days]	5.3 (4.0)	4.0 (2.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Exercise
	Comments	The null hypothesis was that there would be no difference between groups for the number of days of stem cell collections.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	T-test and chi-squared to check for equivalence of groups for age, race and gender.
Statistical Test of Hypothesis	p-Value	<0.025
	Comments	Bonferroni adjusted p-value for multiple comparisons.
	Method	ANOVA
	Comments	This is minus 9 (4 exercise, 5 usual care) participants who were unresponsive to Epoetin Alfa and included participants in short and long study.

8. Primary Outcome

Title	Total Number of Days of Stem Cell Collection (Long Term)
Time Frame	up to 30 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Usual Care	Exercise
Arm/Group Description	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	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.
Measure Participants	34	35
Mean (Standard Deviation) [Days]	4.9 (3.1)	4.5 (3.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Exercise
	Comments	The null hypothesis was that there would be no difference between groups for the number of days of stem cell collections.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	T-test and chi-squared to check for equivalence of groups for age, race and gender.
Statistical Test of Hypothesis	p-Value	<0.025
	Comments	Bonferroni adjusted p-value for multiple comparisons.
	Method	ANOVA
	Comments	This is minus 9 (4 exercise, 5 usual care) participants who were unresponsive to Epoetin Alfa and included participants in short and long study.

9. Secondary Outcome

Title	Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Short Term)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Usual Care	Exercise
Arm/Group Description	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	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.
Measure Participants	28	23
Baseline	12.1 (1.6)	11.6 (1.7)
Before transplantation	10.8 (1.5)	11.0 (1.6)
During transplantation	10.1 (0.7)	10.4 (0.9)
At discharge	10.6 (1.4)	10.6 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, Exercise
	Comments	The null hypothesis was that there would be no difference between groups for the number of platelet transfusions.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	T-test and chi-squared to check for equivalence of groups for age, race and gender.
Statistical Test of Hypothesis	p-Value	<0.025
	Comments	Bonferroni adjusted p-value for multiple comparisons.
	Method	ANOVA
	Comments

10. Secondary Outcome

Title	Hemoglobin Levels Before Chemotherapy and During Transplantation Period (Long Term)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Usual Care	Exercise
Arm/Group Description	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	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.
Measure Participants	34	35
Baseline	11.5 (1.8)	11.7 (1.8)
Before Transplantation	12.0 (1.6)	12.0 (1.4)
During Transplanation	10.8 (1.1)	10.8 (1.1)
At Discharge	10.9 (1.4)	11.0 (1.3)

Adverse Events

Time Frame	up to 30 weeks
Adverse Event Reporting Description	All participants included in the Short and Long Term Analysis populations. Other (non-serious)Adverse Events were not collected for this study.
Arm/Group Title	Usual Care		Exercise
Arm/Group Description	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		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.
All Cause Mortality
	Usual Care		Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Usual Care		Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/62 (27.4%)		25/58 (43.1%)
Blood and lymphatic system disorders
Anemia	1/62 (1.6%)		1/58 (1.7%)
Hyponatremia	1/62 (1.6%)		5/58 (8.6%)
Cardiac disorders
Atrial fibrillation	0/62 (0%)		1/58 (1.7%)
Myocardial infarction	0/62 (0%)		1/58 (1.7%)
Gastrointestinal disorders
Mucositis / diarrhea	1/62 (1.6%)		1/58 (1.7%)
Ruptured diverticulum	0/62 (0%)		1/58 (1.7%)	59
General disorders
Death	1/62 (1.6%)		1/58 (1.7%)
Dehydration	2/62 (3.2%)		1/58 (1.7%)
Fluid overload	1/62 (1.6%)		0/58 (0%)
Pain	1/62 (1.6%)		1/58 (1.7%)
Syncope	1/62 (1.6%)		0/58 (0%)
Immune system disorders
Neutropenic fever	11/62 (17.7%)		8/58 (13.8%)
Infections and infestations
Infection / sepsis	5/62 (8.1%)		1/58 (1.7%)
Pneumonia	5/62 (8.1%)		1/58 (1.7%)
Rectal abcesses	1/62 (1.6%)		0/58 (0%)
Metabolism and nutrition disorders
Hyperglycemia	3/62 (4.8%)		3/58 (5.2%)
Musculoskeletal and connective tissue disorders
Compression fracture	0/62 (0%)		1/58 (1.7%)
Renal and urinary disorders
Renal failure	1/62 (1.6%)		0/58 (0%)
Renal stone	1/62 (1.6%)		0/58 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory distress	1/62 (1.6%)		0/58 (0%)
Vascular disorders
Deep Vein Thrombosis (DVT)	11/62 (17.7%)		10/58 (17.2%)
Pulmonary embolus	3/62 (4.8%)		2/58 (3.4%)
Other (Not Including Serious) Adverse Events
	Usual Care		Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

Patients with hemoglobin <8 g/dl received RBC transfusions according to the transplantation protocol. Analysis may have missed specific disease-related influences on hemoglobin. Randomization should have distributed disease risks equally for groups.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.