Use of Hyperbaric Oxygen Therapy to Improve Umbilical Cord Blood Stem Cell Homing and Subsequent Engraftment

• Sponsor: University of Kansas Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02099266
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arm: 1
• Duration (Months): 32
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

By doing this study, researchers hope to learn the following:

• If providing hyperbaric oxygen (HBO) therapy prior to an umbilical cord blood (UBC) transplant will help to improve the homing process

• The safety of HBO administration in the setting of the UBC transplant

• The effects of HBO therapy on the engraftment process

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome (MDS); Hodgkins Lymphoma; Non-Hodgkins Lymphoma	Device: Administration of hyperbaric oxygen	N/A

Detailed Description

Research has suggested that high levels of erythropoietin (EPO) decreases the ability of infused umbilical cord stem cells to home to the bone marrow. The investigators will investigate the use of hyperbaric oxygen (HBO) therapy to decrease the plasma concentrations of EPO prior to UBC transplant and evaluate the resulting impact on UBC homing.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study to Determine the Safety and Efficacy of Using Hyperbaric Oxygen Therapy to Improve Umbilical Cord Blood Stem Cell Homing and Subsequent Engraftment
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hyperbaric Oxygen Treatment Administration of hyperbaric oxygen the morning of UCB transplant.	Device: Administration of hyperbaric oxygen; Hyperbaric oxygen at 2.5 atmospheres absolute (ATA) for a total of 2 hours; Other Names: Monoplace Hyperbaric Chamber Model 3200 and 3200R

Outcome Measures

Primary Outcome Measures

1. Safety of HBO Administration in the Setting of UCB Stem Cell Transplantation [Toxicity assessment with 24hrs of treatment]

   Treatment limiting toxicities are defined as the occurrence of any of the following complications within 24hrs of treatment: pneumothorax, death, irreversible grade III or any grade IV toxicity that is determined by the treating physician to be related to HBO therapy.

Secondary Outcome Measures

1. Determine the Effects of HBO Therapy on Neutrophil Count Recovery. [Daily measurement of neutrophil counts up to 90 days post transplant.]

   Time in days until neutrophil count recovery is achieved; neutrophil count recovery is defined as three consecutive days of achieving a neutrophil level >/= 500 u/L.

2. Proportion of Reduced Intensity Conditioning Participants With Complete Engraftment. [28 days]

   Complete engraftment is defined as as marrow reconstitution of greater than 90% of donor cells. Degree of engraftment will be determined through bone marrow chimerism assessment at either day 21 or day 28.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 17 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Voluntary written informed consent

• Subjects must be >/= 17 yrs and </= 70 yrs for non-myeloablative transplant

• Subjects must be >/= 17 yrs and </= 55 yrs for myeloablative transplant

• Subjects with Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Myelodysplastic Syndrome (MDS), Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL) who are considered for UCB transplant

• Use of approved form of contraception

• Karnofsky performance status of >/= 70%

• Adequate hepatic, renal, pulmonary and cardiac function. Criteria include:

• ALT (alanine aminotransferase), AST (aspartate aminotransferase: < 4x IULN (institutional upper limit of normal)

• Total bilirubin </= 2 mg/dL

• Serum creatinine < 2.0 mg/dL

• Left ventricular ejection fraction >/= 45%

• FEV1 (forced expiratory volume), FVC (forced vital capacity) and DLCD (diffusing capacity of lung for carbon monoxide) >/= 50% of predicted value (corrected to serum hemoglobin)

Exclusion Criteria:

• Pregnancy or breast feeding

• Severe chronic obstructive pulmonary disease requiring oxygen supplementation

• History of spontaneous pneumothorax

• History of seizures

• Claustrophobia

• Asthma

• Uncontrolled viral or bacterial infection at the time of enrollment

• Active or recent (prior 6 months) invasive fungal infection without interdisciplinary consult and approval

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Kansas Medical Center	Kansas City	Kansas	United States	66160

Sponsors and Collaborators

• University of Kansas Medical Center

Investigators

• Principal Investigator: Omar Aljitawi, MD, University of Kansas Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Kansas Medical Center
• ClinicalTrials.gov Identifier: NCT02099266
• Other Study ID Numbers: BMT-2011-08-01
• First Posted: Mar 28, 2014
• Last Update Posted: Jun 12, 2017
• Last Verified: May 1, 2017

• Keywords provided by University of Kansas Medical Center: Umbilical Cord Blood (UCB) Stem Cell Transplant; Hyperbaric oxygen; Leukemia; Lymphoma; MDS
• Additional relevant MeSH terms: Lymphoma; Leukemia; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes

Study Results

Participant Flow

Arm/Group Title	Hyperbaric Oxygen Treatment
Arm/Group Description	Administration of hyperbaric oxygen the morning of UCB transplant. Administration of hyperbaric oxygen: Hyperbaric oxygen at 2.5 atmospheres absolute (ATA) for a total of 2 hours
Period Title: Overall Study
STARTED	15
COMPLETED	15
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Hyperbaric Oxygen Treatment
Arm/Group Description	Administration of hyperbaric oxygen the morning of UCB transplant. Administration of hyperbaric oxygen: Hyperbaric oxygen at 2.5 atmospheres absolute (ATA) for a total of 2 hours
Overall Participants	15
Age (Count of Participants)
<=18 years	1 6.7%
Between 18 and 65 years	13 86.7%
>=65 years	1 6.7%
Sex: Female, Male (Count of Participants)
Female	6 40%
Male	9 60%

Outcome Measures

1. Primary Outcome

Title	Safety of HBO Administration in the Setting of UCB Stem Cell Transplantation
Description	Treatment limiting toxicities are defined as the occurrence of any of the following complications within 24hrs of treatment: pneumothorax, death, irreversible grade III or any grade IV toxicity that is determined by the treating physician to be related to HBO therapy.
Time Frame	Toxicity assessment with 24hrs of treatment

Outcome Measure Data

Analysis Population Description

One patient treatment was shortened by approximately 10 minutes because of nausea attributed to concomitant medications.

Arm/Group Title	Hyperbaric Oxygen Treatment
Arm/Group Description	Administration of hyperbaric oxygen the morning of UCB transplant. Administration of hyperbaric oxygen: Hyperbaric oxygen at 2.5 atmospheres absolute (ATA) for a total of 2 hours
Measure Participants	15
grade IV leukopenia	15 100%
grade III/IV neutropenia	12 80%
grade III/IV anemia	12 80%
grade III/IV thrombocytopenia	13 86.7%

2. Secondary Outcome

Title	Determine the Effects of HBO Therapy on Neutrophil Count Recovery.
Description	Time in days until neutrophil count recovery is achieved; neutrophil count recovery is defined as three consecutive days of achieving a neutrophil level >/= 500 u/L.
Time Frame	Daily measurement of neutrophil counts up to 90 days post transplant.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reduced-Intensity Conditioning	Myeloablative Conditioning
Arm/Group Description	Reduced-Intensity (also referred to as: "Non-myeloablative") transplant patients will receive the following chemotherapeutic agents and radiation on the respective days: Day -6 : fludarabine 40mg/m2 (milligram per meter squared) intravenously (IV), cyclophosphamide 50mg/kg IV, and mesna 50mg/kg IV Day-5 to -2: fludarabine 40mg/m2 intravenously (IV) Day -1: Total body irradiation (TBI) 200 centrigray (cGy)	Myeloablative transplant patients will receive the following chemotherapeutic agents and radiation on the respective days: Day -10, -9, and -8: Fludarabine (25 mg/m2 IV) IV Day -7, -6, -5, and -4: Total body irradiation 165 cGy twice daily Day -3 and -2: Cyclophosphamide (60 mg/kg/day ) and mesna 50mg/kg/day (milligrams per kilogram per day) IV
Measure Participants	9	6
Median (Full Range) [Days]	7	24.5

3. Secondary Outcome

Title	Proportion of Reduced Intensity Conditioning Participants With Complete Engraftment.
Description	Complete engraftment is defined as as marrow reconstitution of greater than 90% of donor cells. Degree of engraftment will be determined through bone marrow chimerism assessment at either day 21 or day 28.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reduced-Intensity Conditioning
Arm/Group Description
Measure Participants	9
Count of Participants [Participants]	7 46.7%

Adverse Events

Time Frame	Adverse clinical events experienced by participants will be collected and reported from initiation of HBO treatment and through engraftment or day +90, whichever comes first.
Arm/Group Title	Hyperbaric Oxygen Treatment
Arm/Group Description	Administration of hyperbaric oxygen the morning of UCB transplant. Administration of hyperbaric oxygen: Hyperbaric oxygen at 2.5 atmospheres absolute (ATA) for a total of 2 hours
All Cause Mortality
	Hyperbaric Oxygen Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Hyperbaric Oxygen Treatment
	Affected / at Risk (%)	# Events
Total	7/15 (46.7%)
Gastrointestinal disorders
Abdominal Pain	1/15 (6.7%)	1
diarrhea	1/15 (6.7%)	1
Vomiting	1/15 (6.7%)	1
General disorders
Fever	2/15 (13.3%)	2
Infections and infestations
Lung infection	1/15 (6.7%)	1
Upper Respiratory infection	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/15 (6.7%)	1
Pulmonary edema	1/15 (6.7%)	1
Other (Not Including Serious) Adverse Events
	Hyperbaric Oxygen Treatment
	Affected / at Risk (%)	# Events
Total	15/15 (100%)
Blood and lymphatic system disorders
Anemia	12/15 (80%)	87
Blood and lymphatic system disorders - Other, specify	4/15 (26.7%)	5
Febrile neutropenia	5/15 (33.3%)	7
Lymph node pain	1/15 (6.7%)	1
Cardiac disorders
Cardiac disorders - Other, specify	2/15 (13.3%)	3
Restrictive cardiomyopathy	1/15 (6.7%)	1
Sinus tachycardia	2/15 (13.3%)	2
Supraventricular tachycardia	1/15 (6.7%)	1
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, specify	1/15 (6.7%)	1
Tinnitus	1/15 (6.7%)	1
Eye disorders
Eye disorders - Other, specify	2/15 (13.3%)	6
Eye pain	1/15 (6.7%)	2
Scleral disorder	2/15 (13.3%)	2
Watering eyes	1/15 (6.7%)	1
Gastrointestinal disorders
Abdominal pain	3/15 (20%)	5
Anal pain	2/15 (13.3%)	3
Bloating	2/15 (13.3%)	2
Constipation	6/15 (40%)	7
Diarrhea	9/15 (60%)	13
Dry mouth	2/15 (13.3%)	2
Dysphagia	1/15 (6.7%)	1
Esophagitis	1/15 (6.7%)	1
Flatulence	1/15 (6.7%)	1
Gastroesophageal reflux disease	3/15 (20%)	3
Hemorrhoids	1/15 (6.7%)	1
Lip pain	1/15 (6.7%)	1
Mucositis oral	6/15 (40%)	7
Nausea	11/15 (73.3%)	16
Oral hemorrhage	1/15 (6.7%)	1
Oral pain	4/15 (26.7%)	4
Toothache	2/15 (13.3%)	3
Vomiting	3/15 (20%)	4
General disorders
Chills	6/15 (40%)	6
Edema face	2/15 (13.3%)	3
Edema limbs	6/15 (40%)	10
Edema trunk	1/15 (6.7%)	1
Facial pain	2/15 (13.3%)	2
Fatigue	8/15 (53.3%)	9
Flu like symptoms	2/15 (13.3%)	3
Gait disturbance	2/15 (13.3%)	3
General disorders and administration site conditions - Other, specify	6/15 (40%)	9
Infusion related reaction	1/15 (6.7%)	1
Localized edema	1/15 (6.7%)	1
Malaise	5/15 (33.3%)	5
Non-cardiac chest pain	1/15 (6.7%)	1
Pain	5/15 (33.3%)	5
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify	3/15 (20%)	4
Immune system disorders
Allergic reaction	2/15 (13.3%)	2
Infections and infestations
Infections and infestations - Other, specify	6/15 (40%)	9
Papulopustular rash	1/15 (6.7%)	1
Pharyngitis	1/15 (6.7%)	1
Sinusitis	1/15 (6.7%)	2
Injury, poisoning and procedural complications
Dermatitis radiation	1/15 (6.7%)	1
Injury, poisoning and procedural complications - Other, specify	1/15 (6.7%)	1
Wound complication	1/15 (6.7%)	1
Investigations
Blood bilirubin increased	4/15 (26.7%)	5
Neutrophil count decreased	12/15 (80%)	70
platelet count decreased	14/15 (93.3%)	114
Weight loss	3/15 (20%)	3
White blood cell decreased	15/15 (100%)	86
Metabolism and nutrition disorders
Acidosis	1/15 (6.7%)	1
Anorexia	4/15 (26.7%)	4
Hyperglycemia	2/15 (13.3%)	2
Hyperglycemia	1/15 (6.7%)	1
Hyperkalemia	1/15 (6.7%)	1
Hypernatremia	1/15 (6.7%)	1
Hypokalemia	7/15 (46.7%)	8
Hypomagnesemia	9/15 (60%)	11
Hyponatremia	2/15 (13.3%)	2
Hypophosphatemia	1/15 (6.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/15 (6.7%)	1
Arthritis	1/15 (6.7%)	1
Back pain	2/15 (13.3%)	2
Bone pain	1/15 (6.7%)	1
Generalized muscle weakness	1/15 (6.7%)	1
Myalgia	3/15 (20%)	3
Neck pain	1/15 (6.7%)	1
Pain in extremity	1/15 (6.7%)	1
Nervous system disorders
Concentration impairment	1/15 (6.7%)	1
Dizziness	2/15 (13.3%)	2
Headache	3/15 (20%)	3
Paresthesia	1/15 (6.7%)	1
Sinus pain	1/15 (6.7%)	2
Somnolence	1/15 (6.7%)	1
Tremor	1/15 (6.7%)	1
Psychiatric disorders
Agitation	1/15 (6.7%)	1
Anxiety	5/15 (33.3%)	6
Depression	3/15 (20%)	3
Hallucinations	1/15 (6.7%)	1
Insomnia	1/15 (6.7%)	1
Renal and urinary disorders
Acute kidney injury	2/15 (13.3%)	2
Cystitis noninfective	1/15 (6.7%)	1
Hematuria	1/15 (6.7%)	1
Renal and urinary disorders - Other, specify	3/15 (20%)	3
Sepsis	1/15 (6.7%)	1
Urinary frequency	1/15 (6.7%)	1
Urinary urgency	1/15 (6.7%)	1
Reproductive system and breast disorders
Genital edema	1/15 (6.7%)	1
Menorrhagia	1/15 (6.7%)	3
Reproductive system and breast disorders - Other, specify	1/15 (6.7%)	1
Vaginal hemorrhage	3/15 (20%)	4
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/15 (6.7%)	1
Cough	3/15 (20%)	4
Dyspnea	3/15 (20%)	3
Hiccups	1/15 (6.7%)	1
Hypoxia	3/15 (20%)	3
Laryngeal inflammation	1/15 (6.7%)	1
Nasal congestion	2/15 (13.3%)	2
Pharyngeal mucositis	1/15 (6.7%)	1
Pleural effusion	1/15 (6.7%)	1
Postnasal drip	2/15 (13.3%)	2
Pulmonary edema	2/15 (13.3%)	3
Respiratory, thoracic and mediastinal disorders - Other, specify	2/15 (13.3%)	6
Sore throat	2/15 (13.3%)	2
Skin and subcutaneous tissue disorders
Dry skin	1/15 (6.7%)	1
Erythroderma	2/15 (13.3%)	2
Pain of skin	1/15 (6.7%)	1
Pruritus	5/15 (33.3%)	7
Rash acneiform	2/15 (13.3%)	2
Rash maculo-papular	6/15 (40%)	12
Skin and subcutaneous tissue disorders - Other, specify	4/15 (26.7%)	6
Skin ulceration	1/15 (6.7%)	1
Vascular disorders
Flushing	1/15 (6.7%)	1
Hypertension	3/15 (20%)	3
Hypotension	3/15 (20%)	3
Thromboembolic event	1/15 (6.7%)	1
Vascular disorders - Other, specify	1/15 (6.7%)	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.