Myeloma
Conditions
Brief summary
Patients with Multiple Myeloma who are considered for high-dose therapy and autologous transplantation at the bone marrow transplant clinic at the Wilmot Cancer Institute (WCI) will be be approached to participate in this trial. Eligible patients who choose to participate will be randomized so that half receive one hyperbaric oxygen therapy session prior to hematopoetic stem cell infusion and half will not. All subjects will have their blood counts monitored closely and time to count recovery will be compared between the two groups.
Interventions
BIOLOGICALHyperbaric Oxygen Therapy
The intervention consists of exposure to hyperbaric oxygen at 2.5 atmospheres absolute (ATA) for a total of 2 hours, in a single see-through hyperbaric chamber, breathing 100% oxygen for 90 minutes while subjects are resting in supine position. During the 2 hours, there will be compression and decompression phases for 15 minutes each in which subjects will be breathing compressed environmental air (21% oxygen).
OTHERNo Hyperbaric Oxygen Therapy
The reference arm will not receive hyperbaric oxygen therapy prior to hematopoietic stem cell transplant.
Sponsors
Omar Aljitawi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Voluntary written informed consent. * Multiple myeloma diagnosis applying the latest criteria by International Working Group. Patients should have received myeloma-directed induction therapy with appropriate response (partial response or better) in newly diagnosed myeloma patients. Multiple myeloma patients who relapse following induction therapy or following prior autologous hematopoietic stem cell transplant are also eligible as far as remission following their first autologous hematopoietic stem cell transplant lasted 12 months or more. * Patients who are considered for high-dose therapy and autologous transplantation at the bone marrow transplant clinic at Wilmot Cancer Institute will be screened for eligibility to enroll in this study and if eligible will be approached to participate. Eligible patients will have the chance to tour the hyperbaric oxygen facility prior to signing the consent form. * Subjects must be ≥ 18 years old and ≤ 75 years old. * Karnofsky performance status (KPS) of ≥ 70%. * Adequate hepatic, cardiac and pulmonary function to be eligible for transplant. Minimum criteria include: * \- Alanine aminotransferase (ALT), aspartate aminotransferase (AST): \< 4x institutional upper limit of normal (IULN) * \- Total bilirubin: ≤ 2.0 mg/dL * \- Ejection fraction (EF) measured by two-dimensional echocardiography (2D-ECHO) or multigated acquisition (MUGA) scan of ≥ 45% * \- Forced expiratory volume at one second (FEV1), forced vital capacity (FVC), and diffusing capacity of lung for carbon monoxide (DLCO) ≥ 50% of predicted value (corrected to serum hemoglobin) * \- Electrocardiogram (EKG) with no clinically significant arrhythmia. * Patients should have New York Heart Association (NYHA) Functional Classification, class I or II (No or mild limitation during ordinary activity). * Patients should be evaluated for fitness for hyperbaric oxygen therapy by a hyperbaric oxygen trained medical professional who is not part of the study team prior to starting preparative regimen. * Women of child-bearing potential should have a negative urine pregnancy test within 4 weeks of starting preparative regimen. * Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days following completion of therapy. Should a woman or partner become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician and the investigator immediately. * A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * \- Has not undergone a hysterectomy or bilateral oophorectomy; or * \- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
Exclusion criteria
* Pregnant or breastfeeding * Severe chronic obstructive pulmonary disease requiring oxygen supplementation * History of spontaneous pneumothorax * Active ear/sinus infection * History of sinus or ear surgery, excluding myringotomy or ear tubes * Claustrophobia * History of seizures * Evidence of pneumothorax or significant pulmonary fibrosis on chest imaging * Prior chest surgery or irradiation * Patients who had intrathecal chemotherapy within 2 weeks of starting preparative regimen or cranial irradiation within 4 weeks of starting preparative regimen * Active infection (viral, fungal, and/or bacterial) * Positive screening for Hepatitis A, B, or C indicating an ongoing infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Transplant to Neutrophil Count Recovery | 100 days | Time from transplant to neutrophil recovery was measured as the first day of absolute neutrophil count \>=0.5 thou/ul after nadir. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Transplant to Absolute Lymphocyte Recovery | 100 days | — |
| Number of Days of Granulocyte Colony-stimulating Factor | 100 days | — |
| Number of Units of Packed Red Blood Cells Received | 100 days | — |
| Length of Hospital Stay | 100 days | — |
| Percentage of Participants With Progressive Free Survival | 1 year | A progressive response is defined as follows: Increase of \> 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be \> 0.5 g/dL)6 Urine M-component and/or (the absolute increase must be \> 200 mg/24 h) Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \> 10 mg/dL Bone marrow plasma cell percentage; the absolute percentage must be \> 10%7 Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of hypercalcaemia (corrected serum calcium \> 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder Anyone who did not have a progressive response was considered as progression free survival. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hyperbaric Oxygen Therapy Subjects on the experimental arm will receive 90 minutes of hyperbaric oxygen therapy approximately six hours prior to hematopoietic stem cell infusion.
Hyperbaric Oxygen Therapy: The intervention consists of exposure to hyperbaric oxygen at 2.5 atmospheres absolute (ATA) for a total of 2 hours, in a single see-through hyperbaric chamber, breathing 100% oxygen for 90 minutes while subjects are resting in supine position. During the 2 hours, there will be compression and decompression phases for 15 minutes each in which subjects will be breathing compressed environmental air (21% oxygen). | 52 |
| No Hyperbaric Oxygen Therapy Subjects on the reference arm will not receive hyperbaric oxygen therapy prior to hematopoietic stem cell infusion.
No Hyperbaric Oxygen Therapy: The reference arm will not receive hyperbaric oxygen therapy prior to hematopoietic stem cell transplant. | 47 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Hyperbaric Oxygen Therapy | No Hyperbaric Oxygen Therapy |
|---|---|---|---|
| Age, Continuous | 62 years | 59 years | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 5 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 93 Participants | 47 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 90 Participants | 46 Participants | 44 Participants |
| Region of Enrollment United States | 99 participants | 52 participants | 47 participants |
| Sex: Female, Male Female | 37 Participants | 21 Participants | 16 Participants |
| Sex: Female, Male Male | 62 Participants | 31 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 47 |
| other Total, other adverse events | 49 / 52 | 39 / 47 |
| serious Total, serious adverse events | 12 / 52 | 9 / 47 |
Outcome results
Primary
Time From Transplant to Neutrophil Count Recovery
Time from transplant to neutrophil recovery was measured as the first day of absolute neutrophil count \>=0.5 thou/ul after nadir.
Time frame: 100 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hyperbaric Oxygen Therapy | Time From Transplant to Neutrophil Count Recovery | 12 days |
| No Hyperbaric Oxygen Therapy | Time From Transplant to Neutrophil Count Recovery | 12 days |
p-value: 0.89Regression, Cox
Secondary
Length of Hospital Stay
Time frame: 100 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hyperbaric Oxygen Therapy | Length of Hospital Stay | 13 Days |
| No Hyperbaric Oxygen Therapy | Length of Hospital Stay | 14 Days |
p-value: 0.5Regression, Cox
Secondary
Number of Days of Granulocyte Colony-stimulating Factor
Time frame: 100 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hyperbaric Oxygen Therapy | Number of Days of Granulocyte Colony-stimulating Factor | 6 Days |
| No Hyperbaric Oxygen Therapy | Number of Days of Granulocyte Colony-stimulating Factor | 6 Days |
p-value: 0.35Regression, Cox
Secondary
Number of Units of Packed Red Blood Cells Received
Time frame: 100 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hyperbaric Oxygen Therapy | Number of Units of Packed Red Blood Cells Received | 0 units |
| No Hyperbaric Oxygen Therapy | Number of Units of Packed Red Blood Cells Received | 0 units |
p-value: 0.77Regression, Cox
Secondary
Percentage of Participants With Progressive Free Survival
A progressive response is defined as follows: Increase of \> 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be \> 0.5 g/dL)6 Urine M-component and/or (the absolute increase must be \> 200 mg/24 h) Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \> 10 mg/dL Bone marrow plasma cell percentage; the absolute percentage must be \> 10%7 Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of hypercalcaemia (corrected serum calcium \> 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder Anyone who did not have a progressive response was considered as progression free survival.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hyperbaric Oxygen Therapy | Percentage of Participants With Progressive Free Survival | 91.3 percentage of participants |
| No Hyperbaric Oxygen Therapy | Percentage of Participants With Progressive Free Survival | 92.6 percentage of participants |
p-value: 0.76Regression, Cox
Secondary
Time From Transplant to Absolute Lymphocyte Recovery
Time frame: 100 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hyperbaric Oxygen Therapy | Time From Transplant to Absolute Lymphocyte Recovery | 12 Days |
| No Hyperbaric Oxygen Therapy | Time From Transplant to Absolute Lymphocyte Recovery | 13 Days |
p-value: 0.03Regression, Cox