Busulfan, Cyclophosphamide, and Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma

• Sponsor: Case Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00941720
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 71
• Location: 1
• Arm: 1
• Actual Duration (Months): 44.6
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

RATIONALE: Giving high-dose chemotherapy before an autologous stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. An autologous stem cell transplant may be able to replace the blood-forming cells that were destroyed by the chemotherapy.

PURPOSE: This phase II trial is studying how well giving busulfan together with cyclophosphamide followed by an autologous stem cell transplant works in treating patients with multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: busulfan; Drug: cyclophosphamide; Procedure: autologous hematopoietic stem cell transplantation	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To compare relapse-free survival and overall survival of patients with multiple myeloma treated with IV busulfan vs historical control patients treated with oral busulfan when administered with cyclophosphamide as a conditioning regimen prior to autologous hematopoietic stem cell transplantation.

Secondary

• To compare pulmonary toxicity rates of IV busulfan vs oral busulfan when administered with cyclophosphamide as a conditioning regimen prior to autologous hematopoietic stem cell transplantation.

OUTLINE: Patients receive high-dose busulfan IV every 6 hours on days -8 to -4 and high-dose cyclophosphamide IV over 4 hours on days -3 and -2. Patients undergo autologous hematopoietic stem cell transplantation on day 0.

After completion of study treatment, patients are followed up periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 71 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study of Outcomes and Toxicity of Busulfex as Part of a High Dose Chemotherapy Preparative Regimen in Autologous Hematopoietic Stem Cell Transplantation for Patients With Plasma Cell Myeloma
• Actual Study Start Date: Jun 11, 2009
• Actual Primary Completion Date: Feb 28, 2013
• Actual Study Completion Date: Feb 28, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Busulfan Treatment

Drug: busulfan; IV busulfan 0.8 mg/kg every 6 hours x 16 doses; Other Names: BSF BU Misulfan Mitosan Myeloleukon Myelosan ; Drug: cyclophosphamide; IV cyclophosphamide 60 mg/kg over 4 hours x 2 days; Other Names: CPM CTX Cytoxan Endoxan Endoxana Enduxan ; Procedure: autologous hematopoietic stem cell transplantation; infusion of autologous hematopoietic stem cells of at least 2.0 x 106 CD34+ cells/kg on day 0

Outcome Measures

Primary Outcome Measures

1. Relapse-free Survival [at 6 months]

   Number of participants without progressive disease at the end of the study period, using the definitions for complete response, partial response and progressive disease from the International Myeloma Working Group .

2. Overall Survival [at 6 months]

   Number of patients alive at the end of the study period

Secondary Outcome Measures

1. Pulmonary Toxicity [At 6 months]

   Toxicity criteria will be assessed and graded according to the National Cancer Institute (NCI) Common Terminology Criteria (CTC) v3.0. Estimated using exact 95% binomial confidence intervals.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA:

• Patients with a diagnosis of plasma cell myeloma

• Patients with cardiac ejection fraction >= 45% or clearance by Cleveland Clinic Faculty (CCF) cardiologist

• Patients with diffusion capacity of carbon monoxide (DLCO) >= 45% predicted or clearance by CCF pulmonologist

• Patient with previously harvested peripheral blood progenitor cells with a minimum of 2 x 10^6 CD 34+ cells/kg harvested

EXCLUSION CRITERIA:

• Patients receiving total body irradiation

• Non-myeloablative/reduced-intensity conditioning

• Pregnant and breast feeding patients

• Human immunodeficiency virus (HIV) positive

• Patients with serum creatinine > 2.0

• Prior Hematopoietic Stem Cell (HSC) transplant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Case Comprehensive Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ronald M. Sobecks, MD, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00941720
• Other Study ID Numbers: CASE1A07
• First Posted: Jul 20, 2009
• Last Update Posted: Jul 24, 2020
• Last Verified: Jul 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Case Comprehensive Cancer Center: stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Cyclophosphamide; Busulfan

Study Results

Participant Flow

Arm/Group Title	Busulfan Treatment
Arm/Group Description	busulfan: IV busulfan 0.8 mg/kg every 6 hours x 16 doses cyclophosphamide: IV cyclophosphamide 60 mg/kg over 4 hours x 2 days autologous hematopoietic stem cell transplantation: infusion of autologous hematopoietic stem cells of at least 2.0 x 106 CD34+ cells/kg on day 0
Period Title: Overall Study
STARTED	71
COMPLETED	57
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	Busulfan Treatment
Arm/Group Description	busulfan: IV busulfan 0.8 mg/kg every 6 hours x 16 doses cyclophosphamide: IV cyclophosphamide 60 mg/kg over 4 hours x 2 days autologous hematopoietic stem cell transplantation: infusion of autologous hematopoietic stem cells of at least 2.0 x 106 CD34+ cells/kg on day 0
Overall Participants	57
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (8)
Sex: Female, Male (Count of Participants)
Female	24 42.1%
Male	33 57.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 1.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	9 15.8%
White	47 82.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	57 100%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	57 100%

Outcome Measures

1. Primary Outcome

Title	Relapse-free Survival
Description	Number of participants without progressive disease at the end of the study period, using the definitions for complete response, partial response and progressive disease from the International Myeloma Working Group .
Time Frame	at 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Busulfan Treatment
Arm/Group Description	busulfan: IV busulfan 0.8 mg/kg every 6 hours x 16 doses cyclophosphamide: IV cyclophosphamide 60 mg/kg over 4 hours x 2 days autologous hematopoietic stem cell transplantation: infusion of autologous hematopoietic stem cells of at least 2.0 x 106 CD34+ cells/kg on day 0
Measure Participants	57
Number [participants]	48 84.2%

2. Primary Outcome

Title	Overall Survival
Description	Number of patients alive at the end of the study period
Time Frame	at 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Busulfan Treatment
Arm/Group Description	busulfan: IV busulfan 0.8 mg/kg every 6 hours x 16 doses cyclophosphamide: IV cyclophosphamide 60 mg/kg over 4 hours x 2 days autologous hematopoietic stem cell transplantation: infusion of autologous hematopoietic stem cells of at least 2.0 x 106 CD34+ cells/kg on day 0
Measure Participants	57
Number [participants]	53 93%

3. Secondary Outcome

Title	Pulmonary Toxicity
Description	Toxicity criteria will be assessed and graded according to the National Cancer Institute (NCI) Common Terminology Criteria (CTC) v3.0. Estimated using exact 95% binomial confidence intervals.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Busulfan Treatment
Arm/Group Description	busulfan: IV busulfan 0.8 mg/kg every 6 hours x 16 doses cyclophosphamide: IV cyclophosphamide 60 mg/kg over 4 hours x 2 days autologous hematopoietic stem cell transplantation: infusion of autologous hematopoietic stem cells of at least 2.0 x 106 CD34+ cells/kg on day 0
Measure Participants	57
Number (95% Confidence Interval) [percentage of participants]	3.5 6.1%

Adverse Events

Time Frame	100 days after off treatment
Arm/Group Title	Busulfan Treatment
Arm/Group Description	busulfan: IV busulfan 0.8 mg/kg every 6 hours x 16 doses cyclophosphamide: IV cyclophosphamide 60 mg/kg over 4 hours x 2 days autologous hematopoietic stem cell transplantation: infusion of autologous hematopoietic stem cells of at least 2.0 x 106 CD34+ cells/kg on day 0
All Cause Mortality
	Busulfan Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Busulfan Treatment
	Affected / at Risk (%)	# Events
Total	12/57 (21.1%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders - other (Relapsed disease)	1/57 (1.8%)	2
General disorders
Death NOS	5/57 (8.8%)	5
Immune system disorders
Allergic reaction - Angioedemia due to ACE Inhibitors	1/57 (1.8%)	1
Infections and infestations
Lung Infection	1/57 (1.8%)	1
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other (patient fell and hit head. Never recovered)	1/57 (1.8%)	2
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome	1/57 (1.8%)	1
Dyspenia	1/57 (1.8%)	1
Laryngeal edema	1/57 (1.8%)	2
Other (Not Including Serious) Adverse Events
	Busulfan Treatment
	Affected / at Risk (%)	# Events
Total	5/57 (8.8%)
Gastrointestinal disorders
Colitis - diverticulitis	1/57 (1.8%)	1
Gastrointestinal disorders - Clostridium difficile in urine and diarrhea	1/57 (1.8%)	1
General disorders
Fever	1/57 (1.8%)	3
Infections and infestations
Catheter related infection	1/57 (1.8%)	1
Respiratory, thoracic and mediastinal disorders
Dyspenia	1/57 (1.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.