Manage Diarrhea in Patients With Multiple Myeloma While Receiving Conditioning Chemotherapy for Autologous SCT

• Sponsor: Mayo Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02619812
• Collaborator: Entera Health, Inc (Industry)
• Enrollment: 4
• Location: 1
• Arms: 4
• Actual Duration (Months): 8
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

For patients who receive a hematopoietic cell transplant (HCT), there is a risk of developing a diarrhea secondary to the chemotherapy which we give. Diarrhea is usually harmless in healthy adults; however, in transplant patients, diarrhea can result in dehydration, negative impact on quality of life, and prolonged hospitalization. The purpose of this study was to see if Colesevelam (Welchol) and Serum-derived bovine immunoglobulin-protein (SBI) result in a change in the frequency or consistency of your bowel movements.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Other: Serum-derived bovine immunoglobulin/protein isolate (SBI); Drug: Colesevelam; Other: Double Placebo	Phase 2

Detailed Description

This was a randomized, double-blind, placebo-controlled pilot study of SBI, colesevelam, and placebo in patients undergoing autologous HSCT for the clinical care of multiple myeloma.

The number of adults undergoing hematopoietic stem cell transplant (HSCT) has grown significantly over the past two decades as a result of the availability of therapies for advanced hematologic and solid tumor malignancies, and the broader selection criteria for eligibility to receive these transplants. Generally, the stem cell transplant procedure consists of administration of chemotherapy and/or radiation therapy to ablate all residual malignancy (called conditioning therapy), followed by intravenous infusion of hematopoietic stem cells to restore bone marrow function. Generally, HSCT has a positive effect on survival, despite serious adverse effects and life-threatening complications.

Diarrhea can affect up to 91% of patients receiving autologous or allogeneic HSCT and is identified by 9% of the patients as the single most debilitating adverse effect post-HSCT. Other commonly encountered symptoms are nausea and vomiting (13%) and mouth sores (42%). The impact of diarrhea can be significant and result in dehydration, negative impact on quality of life, prolonged hospitalization with an increased cost and risk, and the diarrhea may be potentially life-threatening.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• Official Title: A Randomized, Placebo-Controlled, Pilot Study of Colesevelam and Serum-Derived Bovine Immunoglobulin/Protein Isolate to Manage Diarrhea in Patients With Multiple Myeloma Receiving Conditioning Chemotherapy for Autologous Stem Cell Transplantation (SCT)
• Actual Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group A: SBI + Placebo Serum-derived bovine immunoglobulin/protein isolate (SBI) 10 grams + placebo twice per day	Other: Serum-derived bovine immunoglobulin/protein isolate (SBI); SBI 10 grams (The subject will take a total of 4 packets of SBI; taken as two packets of SBI twice a day mixed with water or blended with certain foods); Other: Double Placebo; Double placebo twice per day (The subject will take a total of 4 packets of placebo and 12 capsules daily taken as 6 capsules twice a day by mouth and two packets of placebo twice a day mixed with water or blended with certain foods).
Active Comparator: Group B: Colesevelam + Placebo Colesevelam 1.875 g + Placebo twice per day	Drug: Colesevelam; Colesevelam 1.875 g (The subject will take a total of 12 capsules of Welchol 1.875g per day; taken as 6 capsules twice a day by mouth).; Other Names: Welchol ; Other: Double Placebo; Double placebo twice per day (The subject will take a total of 4 packets of placebo and 12 capsules daily taken as 6 capsules twice a day by mouth and two packets of placebo twice a day mixed with water or blended with certain foods).
Active Comparator: Group C: Colesevelam + SBI Colesevelam 1.875 g + Serum-derived bovine immunoglobulin/protein isolate (SBI) 10 grams twice per day	Other: Serum-derived bovine immunoglobulin/protein isolate (SBI); SBI 10 grams (The subject will take a total of 4 packets of SBI; taken as two packets of SBI twice a day mixed with water or blended with certain foods); Drug: Colesevelam; Colesevelam 1.875 g (The subject will take a total of 12 capsules of Welchol 1.875g per day; taken as 6 capsules twice a day by mouth).; Other Names: Welchol
Placebo Comparator: Group D: Double Placebo Double placebo twice per day	Other: Double Placebo; Double placebo twice per day (The subject will take a total of 4 packets of placebo and 12 capsules daily taken as 6 capsules twice a day by mouth and two packets of placebo twice a day mixed with water or blended with certain foods).

Outcome Measures

Primary Outcome Measures

1. Stool Frequency [30 days]

   Stool frequency was self reported in a daily bowel pattern diary for 30 days.

2. Stool Consistency [30 days]

   The subjects rated their stool consistency using the Bristol Stool Scale. The Bristol Stool Scale is a medical aid designed to classify the form of human feces into seven categories or types. Types 1 and 2 indicate constipation with 3 and 4 being the "ideal stools" especially the latter, as they are the easiest to defecate, and 5-7 tending towards diarrhea.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age ≥18 years, male or female

• Diagnosis: multiple myeloma undergoing Autologous Stem Cell Transplantation (SCT)

• Planning to receive conditioning chemotherapy (Melphalan) for autologous stem cell transplantation and standard prophylactic antibiotics treatment.

• Can drink 200ml of mannitol and agrees to undergo stool, urine, and blood checks 3 times during the study.

• Agrees and able to take the investigational products or placebo starting from the day of completing conditioning therapy for a total of 4 weeks

Exclusion Criteria:

• Patients with history of inflammatory bowel disease will be excluded from the study.

• Patients with prior GI tract surgical (small or large bowel) resections

• The concurrent presence of systemic light chain amyloidosis

• Subject has known allergy or intolerance to beef or to any ingredient used in the product

• Women who are pregnant, breast-feeding and of child-bearing potential

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• Entera Health, Inc

Investigators

• Principal Investigator: Michael Camilleri, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Michael Camilleri, Professor of Medicine, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02619812
• Other Study ID Numbers: 15-006205
• First Posted: Dec 2, 2015
• Last Update Posted: Jun 14, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Diarrhea; Colesevelam Hydrochloride; Immunoglobulins; Immunoglobulins, Intravenous; Antibodies

Study Results

Participant Flow

Recruitment Details	The subjects were recruited from Mayo Clinic in Rochester, Minnesota.
Pre-assignment Detail	A total of 4 subjects were enrolled. Two subjects were randomized to placebo/placebo, and one subject was randomized to colesevelam/Serum-derived bovine immunoglobulin/protein isolate (SBI). One subject was consented, but never randomized/accrued.

Arm/Group Title	Group A: SBI + Placebo	Group B: Colesevelam + Placebo	Group C: Colesevelam + SBI	Group D: Double Placebo
Arm/Group Description	SBI 10 grams + placebo twice per day.	Colesevelam 1.875 g + Placebo twice per day	Colesevelam 1.875 g + SBI 10 grams twice per day.	Double Placebo: Double placebo twice per day (Subjects took a total of 4 packets of placebo and 12 capsules daily taken as 6 capsules twice a day by mouth and two packets of placebo twice a day mixed with water or blended with certain foods).
Period Title: Overall Study
STARTED	0	0	1	2
COMPLETED	0	0	0	0
NOT COMPLETED	0	0	1	2

Baseline Characteristics

Arm/Group Title	Group A: SBI + Placebo	Group B: Colesevelam + Placebo	Group C: Colesevelam + SBI	Group D: Double Placebo	Total
Arm/Group Description	SBI 10 grams + placebo twice per day.	Colesevelam 1.875 g + Placebo twice per day	Colesevelam 1.875 g + SBI 10 grams twice per day.	Double Placebo: Double placebo twice per day (Subjects took a total of 4 packets of placebo and 12 capsules daily taken as 6 capsules twice a day by mouth and two packets of placebo twice a day mixed with water or blended with certain foods).	Total of all reporting groups
Overall Participants	0	0	1	2	3
Age (Count of Participants)
<=18 years	0 NaN	0 NaN	0 0%
Between 18 and 65 years	1 Infinity	2 Infinity	3 300%
>=65 years	0 NaN	0 NaN	0 0%
Sex: Female, Male (Count of Participants)
Female	0 NaN	0 NaN	0 0%
Male	1 Infinity	2 Infinity	3 300%
Region of Enrollment (participants) [Number]
United States	1 Infinity	2 Infinity	3 300%

Outcome Measures

1. Primary Outcome

Title	Stool Frequency
Description	Stool frequency was self reported in a daily bowel pattern diary for 30 days.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Group A: SBI + Placebo	Group B: Colesevelam + Placebo	Group C: Colesevelam + SBI	Group D: Double Placebo
Arm/Group Description	SBI 10 grams + placebo twice per day.	Colesevelam 1.875 g + Placebo twice per day	Colesevelam 1.875 g + SBI 10 grams twice per day.	Double Placebo: Double placebo twice per day (Subjects took a total of 4 packets of placebo and 12 capsules daily taken as 6 capsules twice a day by mouth and two packets of placebo twice a day mixed with water or blended with certain foods).
Measure Participants	0	0	0	0

2. Primary Outcome

Title	Stool Consistency
Description	The subjects rated their stool consistency using the Bristol Stool Scale. The Bristol Stool Scale is a medical aid designed to classify the form of human feces into seven categories or types. Types 1 and 2 indicate constipation with 3 and 4 being the "ideal stools" especially the latter, as they are the easiest to defecate, and 5-7 tending towards diarrhea.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Group A: SBI + Placebo	Group B: Colesevelam + Placebo	Group C: Colesevelam + SBI	Group D: Double Placebo
Arm/Group Description	SBI 10 grams + placebo twice per day.	Colesevelam 1.875 g + Placebo twice per day	Colesevelam 1.875 g + SBI 10 grams twice per day.	Double Placebo: Double placebo twice per day (Subjects took a total of 4 packets of placebo and 12 capsules daily taken as 6 capsules twice a day by mouth and two packets of placebo twice a day mixed with water or blended with certain foods).
Measure Participants	0	0	0	0

Adverse Events

Time Frame	30 days
Arm/Group Title	Group A: SBI + Placebo		Group B: Colesevelam + Placebo		Group C: Colesevelam + SBI		Group D: Double Placebo
Arm/Group Description	SBI 10 grams + placebo twice per day.		Colesevelam 1.875 g + Placebo twice per day		Colesevelam 1.875 g + SBI 10 grams twice per day.		Double Placebo: Double placebo twice per day (Subjects took a total of 4 packets of placebo and 12 capsules daily taken as 6 capsules twice a day by mouth and two packets of placebo twice a day mixed with water or blended with certain foods).
All Cause Mortality
	Group A: SBI + Placebo		Group B: Colesevelam + Placebo		Group C: Colesevelam + SBI		Group D: Double Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Group A: SBI + Placebo		Group B: Colesevelam + Placebo		Group C: Colesevelam + SBI		Group D: Double Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/1 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Group A: SBI + Placebo		Group B: Colesevelam + Placebo		Group C: Colesevelam + SBI		Group D: Double Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		1/1 (100%)		2/2 (100%)
Gastrointestinal disorders
Nausea	0/0 (NaN)	0	0/0 (NaN)	0	0/1 (0%)	0	2/2 (100%)	2
Vomiting	0/0 (NaN)	0	0/0 (NaN)	0	0/1 (0%)	0	1/2 (50%)	1
Stomach cramps	0/0 (NaN)	0	0/0 (NaN)	0	0/1 (0%)	0	1/2 (50%)	1
Constipation	0/0 (NaN)	0	0/0 (NaN)	0	0/1 (0%)	0	1/2 (50%)	1
Abdominal bloating	0/0 (NaN)	0	0/0 (NaN)	0	1/1 (100%)	1	0/2 (0%)	0
General disorders
Fatigue	0/0 (NaN)	0	0/0 (NaN)	0	0/1 (0%)	0	1/2 (50%)	1
Reproductive system and breast disorders
Testicular pain	0/0 (NaN)	0	0/0 (NaN)	0	0/1 (0%)	0	1/2 (50%)	1

Limitations/Caveats

This study was terminated early due to difficulty recruiting subjects; pill burden and nausea were barriers to study continuation for subjects accrued. Data were not collected.

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.