Study of CLAG + Selinexor in Relapsed or Refractory Acute Myeloid Leukemia
Study Details
Study Description
Brief Summary
Selinexor has shown single-agent activity in a current phase I study enrolling patients with relapsed/refractory AML with durable complete remissions (CR), complete remissions with incomplete hematologic recovery (CRi), partial remissions (PR), and stable disease (SD) observed. Furthermore, common toxicities included nausea, fatigue, and anorexia and were manageable with supportive care agents. Additionally, CLAG chemotherapy has proven activity in relapsed and refractory AML, and has been shown to be a relatively well tolerated regimen without significant non-hematologic toxicity. Given the established role of CLAG chemotherapy, the single agent activity of selinexor, and their non-overlapping toxicities, the investigators propose a phase I/II open label study of selinexor in combination with CLAG for the treatment of patients with relapsed/refractory AML.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase I Schedule A (selinexor) Selinexor will be dosed on Days 1, 5, 10, and 12 of the 28-day cycle. All doses will be 60 mg each PO. Single agent selinexor maintenance may be given at 60 mg on Days 1, 8, 15, and 22 (4 doses per 28 day cycle). Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. |
Drug: Selinexor
Other Names:
Drug: Cladribine
Other Names:
Drug: G-CSF
Other Names:
Drug: Cytarabine
Other Names:
Procedure: Bone marrow biopsy
Other Names:
|
| Experimental: Phase I Schedule B (selinexor) Selinexor will be dosed on Days 1, 5, 10, 12, 17, and 19 of the 28-day cycle. All doses will be 60 mg each PO. Single agent selinexor maintenance may be given at 60 mg on Days 1, 8, 15, and 22 (4 doses per 28 day cycle). Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. |
Drug: Selinexor
Other Names:
Drug: Cladribine
Other Names:
Drug: G-CSF
Other Names:
Drug: Cytarabine
Other Names:
Procedure: Bone marrow biopsy
Other Names:
|
| Experimental: Phase II (selinexor) Selinexor will be given at the schedule as determined in Phase 1. Single agent selinexor maintenance may be given at 60 mg on Days 1, 8, 15, and 22 (4 doses per 28 day cycle). Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. |
Drug: Selinexor
Other Names:
Drug: Cladribine
Other Names:
Drug: G-CSF
Other Names:
Drug: Cytarabine
Other Names:
Procedure: Bone marrow biopsy
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Safety and Tolerability of Treatment as Measured by Incidence of Grade 3-4 Adverse Events Occurring in >5% of Participants [From start of treatment until 30 days following last day of study treatment or until the start of a subsequent treatment for AML, whichever came first (41 days)]
-All adverse events will be classified using the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0
- Complete Remission Rate (CR + CRi) [Median follow-up of 34 days]
Morphologic complete remission (CR): neutrophil count > 1.0 x 109 /L, platelet count ≥ 100 x 109/L, < 5% bone marrow blasts by morphologic review, no Auer rods, no evidence of extramedullary disease. (No requirements for marrow cellularity, hemoglobin concentration). Morphologic complete remission with incomplete blood count recovery (CRi): same as CR but ANC may be <1000/mcl or platelet count <100,000/mcl Participants in the phase I portion of the study, treated at the MTD will count towards the phase II accrual goal for evaluation of the primary endpoint.
Secondary Outcome Measures
- Time to Platelet Engraftment [56 days]
-Time to platelet engraftment: Defined as the date of the first dose of study drug to the date that the platelet count is >100,000/mm^3 in the absence of platelet transfusions.
- Time to Neutrophil Engraftment [Up to 2 years]
-Time to neutrophil engraftment: Defined as the date of the first dose of study drug to the date that the absolute neutrophil count is >1,000/mm3
- Event-free Survival [Up to 2 years (median follow-up of 307 days)]
Event-free survival (EFS): Defined as the interval from the date of first dose of study drug to date of treatment failure including progressive disease, recurrence, or discontinuation for any reason (including toxicity, patient preference, initiation of new treatment without documented progression, or death due to any cause).
- Duration of Remission [Up to 2 years]
-Duration of remission (DOR): Defined as the interval from the date complete remission is documented to the date of recurrence.
- Relapse-free Survival [Median follow-up of 307 days]
Relapse-free survival (RFS): For patients achieving a complete remission, defined as the interval from the date of first documentation of a leukemia free state to date of recurrence or death due to any cause.
- Overall Survival [Up to 2 years (median follow-up of 307 days)]
Overall survival (OS): Defined as the date of first dose of study drug to the date of death from any cause. OS will be evaluated at 3 month intervals for at least 12 months and up to a maximum of 2 years.
- Number of Participants Who Were Able to Undergo Hematopoietic Stem Cell Transplantation [Up to 2 years (median follow-up of 307 days)]
Allogeneic stem cell transplant utilization: the number of patients proceeding to allogeneic transplant within 2 months following end of study without any additional salvage therapy following study treatment.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed AML (defined using WHO criteria) with one of the following:
-
Primary refractory disease following ≤ 2 cycles of induction chemotherapy, or
-
First relapse with no prior unsuccessful salvage chemotherapy, or
-
Relapsed or refractory to hypomethylating agent, defined as a lack of response, disease progression, loss of response, or intolerance as deemed by the study investigator
-
Age between 18 and 70 years old.
-
ECOG performance status ≤ 3
-
Adequate organ function as defined below:
-
AST(SGOT), ALT(SGPT), total bilirubin ≤ 2 x IULN except when in the opinion of treating physician is due to direct involvement of leukemia (eg. hepatic infiltration or biliary obstruction due to leukemia) or Gilbert's disease
-
Creatinine clearance >50 ml/min, calculated using the formula of Cockroft and Gault: (140-Age) x Mass (kg) / (72 x Creatinine mg/dL); multiply by 0.85 if female.
-
Left ventricular ejection fraction of ≥ 40% by MUGA scan or echocardiogram
-
To ensure that no patient will receive a dose of selinexor >70mg/m2, body surface area (BSA) calculated by Dubois method must be >1.43 m2
-
Patients should not become pregnant or father a baby while on this study because the drugs in this study can affect an unborn baby. Women should not breastfeed a baby while on this study. It is important patients understand the need to use birth control while on this study. It is not anticipated that female patients enrolling in this study will be able to conceive. However, in the rare event that this is possible, female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose.
-
Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
-
Acute promyelocytic leukemia (AML with t(15;17)(q22;q11) and variants).
-
Previous treatment with CLAG or other chemotherapy regimen containing both cladribine and cytarabine.
-
Colony stimulating factors within 2 weeks of study.
-
Active graft versus host disease (GVHD) after allogeneic stem cell transplantation. At least 2 months must have elapsed since completion of an allogeneic stem cell transplantation.
-
Less than 2 weeks from the completion of any previous cytotoxic chemotherapy (with the exception of hydroxyurea).
-
Concurrent active malignancy under treatment except prostate or breast cancer undergoing treatment with hormonal therapy.
-
Treatment with any investigational agent within three weeks prior to first dose in this study.
-
Active CNS involvement with leukemia.
-
Unstable cardiovascular function:
-
symptomatic ischemia, or
-
uncontrolled clinically significant conduction abnormalities (i.e. ventricular tachycardia on antiarrhythmics are excluded and 1st degree AV block or asymptomatic LAFB/RBBB will not be excluded), or
-
congestive heart failure (CHF) of NYHA class ≥3, or
-
myocardial infarction (MI) within 3 months
-
A history of allergic reactions attributed to compounds of similar chemical or biologic composition to KPT-330 or other agents used in the study.
-
Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable.
-
Any medical condition which, in the investigator's opinion, could compromise the patient's safety.
-
Pregnant and/or breastfeeding. Patient must have a negative urine pregnancy test within 5 days of study entry.
-
Unable to swallow tablets, or diagnosed malabsorption syndrome, or any other disease significantly affecting gastrointestinal function.
-
Known active hepatitis B virus (HBV) or C virus (HCV) infection; or known to be positive for HCV ribonucleic acid (RNA) or HBsAg (HBV surface antigen).
-
Known human immunodeficiency virus (HIV) infection.
-
Serious psychiatric or medical conditions that could interfere with treatment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
Sponsors and Collaborators
- Washington University School of Medicine
- Karyopharm Therapeutics Inc
Investigators
- Principal Investigator: Geoffrey Uy, M.D., Washington University School of Medicine
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 201505084
Study Results
Participant Flow
| Recruitment Details | The study was opened to allow participant enrollment on 06/16/2015 and the study was closed to participant enrollment on 01/22/2018. |
|---|---|
| Pre-assignment Detail | Principal Investigator decided not to escalate to Schedule B dosing in the interest of generating additional safety data Maintenance Phase patients are patients who were enrolled & treated in Phase I Schedule A or Phase II but met certain criteria to receive maintenance selinexor. Their data will only be included in adverse event results. |
| Arm/Group Title | Phase I Schedule A (Selinexor) | Phase I Schedule B (Selinexor) | Phase II (Selinexor) | Selinexor Maintenance Phase (Optional) |
|---|---|---|---|---|
| Arm/Group Description | Selinexor will be dosed on Days 1, 5, 10, and 12 of the 28-day cycle. All doses will be 60 mg each PO. Single agent selinexor maintenance may be given at 60 mg on Days 1, 8, 15, and 22 (4 doses per 28 day cycle). Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. | Selinexor will be dosed on Days 1, 5, 10, 12, 17, and 19 of the 28-day cycle. All doses will be 60 mg each PO. Single agent selinexor maintenance may be given at 60 mg on Days 1, 8, 15, and 22 (4 doses per 28 day cycle). Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. | Selinexor will be given at the schedule as determined in Phase 1. Single agent selinexor maintenance may be given at 60 mg on Days 1, 8, 15, and 22 (4 doses per 28 day cycle). Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. | These patients were enrolled and treated in the Phase I Schedule A Arm or the Phase II Arm and if they met the requirements below then they were able to receive maintenance selinexor Available for patients who have achieved a CR or CRi based on post-treatment bone marrow assessment at the time of hematopoietic recovery and are either (1) transplant ineligible or (2) do not have a stem cell transplant donor available 60 mg selinexor on Days 1, 8, 15, and 22 of a 28-day cycle |
| Period Title: Dose Escalation Phase | ||||
| STARTED | 6 | 0 | 34 | 0 |
| COMPLETED | 6 | 0 | 30 | 0 |
| NOT COMPLETED | 0 | 0 | 4 | 0 |
| Period Title: Dose Escalation Phase | ||||
| STARTED | 0 | 0 | 0 | 2 |
| COMPLETED | 0 | 0 | 0 | 2 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Phase I Schedule A (Selinexor) | Phase I Schedule B (Selinexor) | Phase II (Selinexor) | Total |
|---|---|---|---|---|
| Arm/Group Description | Selinexor will be dosed on Days 1, 5, 10, and 12 of the 28-day cycle. All doses will be 60 mg each PO. Single agent selinexor maintenance may be given at 60 mg on Days 1, 8, 15, and 22 (4 doses per 28 day cycle). Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. | Selinexor will be dosed on Days 1, 5, 10, 12, 17, and 19 of the 28-day cycle. All doses will be 60 mg each PO. Single agent selinexor maintenance may be given at 60 mg on Days 1, 8, 15, and 22 (4 doses per 28 day cycle). Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. | Selinexor will be given at the schedule as determined in Phase 1. Single agent selinexor maintenance may be given at 60 mg on Days 1, 8, 15, and 22 (4 doses per 28 day cycle). Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. | Total of all reporting groups |
| Overall Participants | 6 | 0 | 34 | 40 |
| Age (years) [Median (Full Range) ] | ||||
| Median (Full Range) [years] |
63.5
|
55
|
55.5
|
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
2
33.3%
|
13
Infinity
|
15
44.1%
|
|
| Male |
4
66.7%
|
21
Infinity
|
25
73.5%
|
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
0
NaN
|
0
0%
|
|
| Not Hispanic or Latino |
6
100%
|
34
Infinity
|
40
117.6%
|
|
| Unknown or Not Reported |
0
0%
|
0
NaN
|
0
0%
|
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
NaN
|
0
0%
|
|
| Asian |
0
0%
|
0
NaN
|
0
0%
|
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
NaN
|
0
0%
|
|
| Black or African American |
0
0%
|
2
Infinity
|
2
5.9%
|
|
| White |
6
100%
|
32
Infinity
|
38
111.8%
|
|
| More than one race |
0
0%
|
0
NaN
|
0
0%
|
|
| Unknown or Not Reported |
0
0%
|
0
NaN
|
0
0%
|
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
6
100%
|
34
Infinity
|
40
117.6%
|
|
Outcome Measures
| Title | Safety and Tolerability of Treatment as Measured by Incidence of Grade 3-4 Adverse Events Occurring in >5% of Participants |
|---|---|
| Description | -All adverse events will be classified using the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0 |
| Time Frame | From start of treatment until 30 days following last day of study treatment or until the start of a subsequent treatment for AML, whichever came first (41 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| -Phase I Schedule A Arm and Phase II Arm data was combined as all participants received the same dose and schedule of the study regimen. |
| Arm/Group Title | Phase I Schedule A and Phase II |
|---|---|
| Arm/Group Description | Selinexor will be dosed on Days 1, 5, 10, and 12 of the 28-day cycle. All doses will be 60 mg each PO. Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. |
| Measure Participants | 40 |
| Lymphocyte count decreased |
32
533.3%
|
| White blood cell decreased |
28
466.7%
|
| Hypophosphatemia |
26
433.3%
|
| Platelet count decreased |
22
366.7%
|
| Neutrophil count decreased |
21
350%
|
| Hyponatremia |
18
300%
|
| Anemia |
14
233.3%
|
| Hyperglycemia |
11
183.3%
|
| Skin infection |
10
166.7%
|
| Febrile neutropenia |
8
133.3%
|
| Sepsis |
8
133.3%
|
| Hypokalemia |
8
133.3%
|
| Lung infection |
7
116.7%
|
| Alanine aminotransferase increased |
5
83.3%
|
| Oral thrush |
4
66.7%
|
| Hypoxia |
4
66.7%
|
| Hypertension |
4
66.7%
|
| Diarrhea |
3
50%
|
| Nausea |
3
50%
|
| Edema limbs |
3
50%
|
| Catheter-related infection |
3
50%
|
| Hematuria |
3
50%
|
| Respiratory failure |
3
50%
|
| Title | Complete Remission Rate (CR + CRi) |
|---|---|
| Description | Morphologic complete remission (CR): neutrophil count > 1.0 x 109 /L, platelet count ≥ 100 x 109/L, < 5% bone marrow blasts by morphologic review, no Auer rods, no evidence of extramedullary disease. (No requirements for marrow cellularity, hemoglobin concentration). Morphologic complete remission with incomplete blood count recovery (CRi): same as CR but ANC may be <1000/mcl or platelet count <100,000/mcl Participants in the phase I portion of the study, treated at the MTD will count towards the phase II accrual goal for evaluation of the primary endpoint. |
| Time Frame | Median follow-up of 34 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| -Phase I Schedule A Arm and Phase II Arm data was combined as all participants received the same dose and schedule of the study regimen. |
| Arm/Group Title | Phase I Schedule A and Phase II |
|---|---|
| Arm/Group Description | Selinexor will be dosed on Days 1, 5, 10, and 12 of the 28-day cycle. All doses will be 60 mg each PO. Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. |
| Measure Participants | 40 |
| Count of Participants [Participants] |
18
300%
|
| Title | Time to Platelet Engraftment |
|---|---|
| Description | -Time to platelet engraftment: Defined as the date of the first dose of study drug to the date that the platelet count is >100,000/mm^3 in the absence of platelet transfusions. |
| Time Frame | 56 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| -Phase I Schedule A Arm and Phase II Arm data was combined as all participants received the same dose and schedule of the study regimen. |
| Arm/Group Title | Phase I Schedule A and Phase II |
|---|---|
| Arm/Group Description | Selinexor will be dosed on Days 1, 5, 10, and 12 of the 28-day cycle. All doses will be 60 mg each PO. Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. |
| Measure Participants | 40 |
| Median (Full Range) [days] |
38
|
| Title | Time to Neutrophil Engraftment |
|---|---|
| Description | -Time to neutrophil engraftment: Defined as the date of the first dose of study drug to the date that the absolute neutrophil count is >1,000/mm3 |
| Time Frame | Up to 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| -Phase I Schedule A Arm and Phase II Arm data was combined as all participants received the same dose and schedule of the study regimen. |
| Arm/Group Title | Phase I Schedule A and Phase II |
|---|---|
| Arm/Group Description | Selinexor will be dosed on Days 1, 5, 10, and 12 of the 28-day cycle. All doses will be 60 mg each PO. Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. |
| Measure Participants | 40 |
| Median (Full Range) [days] |
28
|
| Title | Event-free Survival |
|---|---|
| Description | Event-free survival (EFS): Defined as the interval from the date of first dose of study drug to date of treatment failure including progressive disease, recurrence, or discontinuation for any reason (including toxicity, patient preference, initiation of new treatment without documented progression, or death due to any cause). |
| Time Frame | Up to 2 years (median follow-up of 307 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| -Phase I Schedule A Arm and Phase II Arm data was combined as all participants received the same dose and schedule of the study regimen. |
| Arm/Group Title | Phase I Schedule A and Phase II |
|---|---|
| Arm/Group Description | Selinexor will be dosed on Days 1, 5, 10, and 12 of the 28-day cycle. All doses will be 60 mg each PO. Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. |
| Measure Participants | 40 |
| Median (95% Confidence Interval) [months] |
6.1
|
| Title | Duration of Remission |
|---|---|
| Description | -Duration of remission (DOR): Defined as the interval from the date complete remission is documented to the date of recurrence. |
| Time Frame | Up to 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| -Phase I Schedule A Arm and Phase II Arm data was combined as all participants received the same dose and schedule of the study regimen. |
| Arm/Group Title | Phase I Schedule A and Phase II |
|---|---|
| Arm/Group Description | Selinexor will be dosed on Days 1, 5, 10, and 12 of the 28-day cycle. All doses will be 60 mg each PO. Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. |
| Measure Participants | 40 |
| Median (95% Confidence Interval) [months] |
9.1
|
| Title | Relapse-free Survival |
|---|---|
| Description | Relapse-free survival (RFS): For patients achieving a complete remission, defined as the interval from the date of first documentation of a leukemia free state to date of recurrence or death due to any cause. |
| Time Frame | Median follow-up of 307 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| -Phase I Schedule A Arm and Phase II Arm data was combined as all participants received the same dose and schedule of the study regimen. |
| Arm/Group Title | Phase I Schedule A and Phase II |
|---|---|
| Arm/Group Description | Selinexor will be dosed on Days 1, 5, 10, and 12 of the 28-day cycle. All doses will be 60 mg each PO. Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. |
| Measure Participants | 18 |
| Median (Full Range) [days] |
152
|
| Title | Overall Survival |
|---|---|
| Description | Overall survival (OS): Defined as the date of first dose of study drug to the date of death from any cause. OS will be evaluated at 3 month intervals for at least 12 months and up to a maximum of 2 years. |
| Time Frame | Up to 2 years (median follow-up of 307 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| -Phase I Schedule A Arm and Phase II Arm data was combined as all participants received the same dose and schedule of the study regimen. |
| Arm/Group Title | Phase I Schedule A and Phase II |
|---|---|
| Arm/Group Description | Selinexor will be dosed on Days 1, 5, 10, and 12 of the 28-day cycle. All doses will be 60 mg each PO. Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. |
| Measure Participants | 40 |
| Median (95% Confidence Interval) [months] |
7.8
|
| Title | Number of Participants Who Were Able to Undergo Hematopoietic Stem Cell Transplantation |
|---|---|
| Description | Allogeneic stem cell transplant utilization: the number of patients proceeding to allogeneic transplant within 2 months following end of study without any additional salvage therapy following study treatment. |
| Time Frame | Up to 2 years (median follow-up of 307 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| -Phase I Schedule A Arm and Phase II Arm data was combined as all participants received the same dose and schedule of the study regimen. |
| Arm/Group Title | Phase I Schedule A and Phase II |
|---|---|
| Arm/Group Description | Selinexor will be dosed on Days 1, 5, 10, and 12 of the 28-day cycle. All doses will be 60 mg each PO. Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. |
| Measure Participants | 40 |
| Count of Participants [Participants] |
24
400%
|
Adverse Events
| Time Frame | Adverse events were collected from start of treatment until 30 days following last day of study treatment or until the start of a subsequent treatment for AML, whichever comes first. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Although there were no dose-limiting toxicities for the first 6 participants treated according to Schedule A dosing, the Principal Investigator decided not to escalate to Schedule B dosing in the interest of generating additional safety data. | |||||||
| Arm/Group Title | Phase I Schedule A (Selinexor) | Phase I Schedule B (Selinexor) | Phase II (Selinexor) | Selinexor Maintenance Phase (Optional) | ||||
| Arm/Group Description | Selinexor will be dosed on Days 1, 5, 10, and 12 of the 28-day cycle. All doses will be 60 mg each PO. Single agent selinexor maintenance may be given at 60 mg on Days 1, 8, 15, and 22 (4 doses per 28 day cycle). Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. | Selinexor will be dosed on Days 1, 5, 10, 12, 17, and 19 of the 28-day cycle. All doses will be 60 mg each PO. Single agent selinexor maintenance may be given at 60 mg on Days 1, 8, 15, and 22 (4 doses per 28 day cycle). Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. | Selinexor will be given at the schedule as determined in Phase 1. Single agent selinexor maintenance may be given at 60 mg on Days 1, 8, 15, and 22 (4 doses per 28 day cycle). Cladribine will be given 5 mg/m^2/day IV once daily on Days 4-8. G-CSF will be given 300 mcg SC once daily on Days 3-8. Cytarabine will be given 2000 mg/m^2/day IV once daily on Days 4-8. Bone marrow biopsy will be performed at baseline, Day 3, at time of hematopoietic recovery, and as clinically indicated to assess treatment response. | Available for patients who have achieved a CR or CRi based on post-treatment bone marrow assessment at the time of hematopoietic recovery and are either (1) transplant ineligible or (2) do not have a stem cell transplant donor available 60 mg selinexor on Days 1, 8, 15, and 22 of a 28-day cycle | ||||
All Cause Mortality |
||||||||
| Phase I Schedule A (Selinexor) | Phase I Schedule B (Selinexor) | Phase II (Selinexor) | Selinexor Maintenance Phase (Optional) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/6 (83.3%) | 0/0 (NaN) | 25/34 (73.5%) | 2/2 (100%) | ||||
Serious Adverse Events |
||||||||
| Phase I Schedule A (Selinexor) | Phase I Schedule B (Selinexor) | Phase II (Selinexor) | Selinexor Maintenance Phase (Optional) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/6 (66.7%) | 0/0 (NaN) | 14/34 (41.2%) | 1/2 (50%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Febrile neutropenia | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Cardiac disorders | ||||||||
| Constrictive pericarditis | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Colitis | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Pancreatitis | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| General disorders | ||||||||
| Fever | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Infections and infestations | ||||||||
| Appendicitis perforated | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Bone infection | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 1/2 (50%) | ||||
| Lung infection | 1/6 (16.7%) | 1/0 (Infinity) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Sepsis | 1/6 (16.7%) | 1/0 (Infinity) | 7/34 (20.6%) | 0/2 (0%) | ||||
| Sinusitis | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Soft tissue infection | 0/6 (0%) | 0/0 (NaN) | 0/34 (0%) | 1/2 (50%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Acidosis | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Nervous system disorders | ||||||||
| Seizure | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Pulmonary edema | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Respiratory failure | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Vascular disorders | ||||||||
| Hypotension | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Phase I Schedule A (Selinexor) | Phase I Schedule B (Selinexor) | Phase II (Selinexor) | Selinexor Maintenance Phase (Optional) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 0/0 (NaN) | 34/34 (100%) | 2/2 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anemia | 2/6 (33.3%) | 2/0 (Infinity) | 14/34 (41.2%) | 0/2 (0%) | ||||
| Febrile neutropenia | 1/6 (16.7%) | 1/0 (Infinity) | 8/34 (23.5%) | 0/2 (0%) | ||||
| Cardiac disorders | ||||||||
| Atrial fibrillation | 2/6 (33.3%) | 2/0 (Infinity) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Atrial flutter | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Left ventricular systolic dysfunction | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Pericardial effusion | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Sinus brachycardia | 0/6 (0%) | 0/0 (NaN) | 8/34 (23.5%) | 0/2 (0%) | ||||
| Sinus tachycardia | 2/6 (33.3%) | 2/0 (Infinity) | 11/34 (32.4%) | 0/2 (0%) | ||||
| Supraventricular tachycardia | 1/6 (16.7%) | 1/0 (Infinity) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Ear pain | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| External ear inflammation | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Cerumen impaction | 0/6 (0%) | 0/0 (NaN) | 0/34 (0%) | 1/2 (50%) | ||||
| Eye disorders | ||||||||
| Blurred vision | 1/6 (16.7%) | 1/0 (Infinity) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Glaucoma | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Intraretinal hemorrhage | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Photophobia | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Vision changes-acuity | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 2/6 (33.3%) | 2/0 (Infinity) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Bloating | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Colitis | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Constipation | 1/6 (16.7%) | 1/0 (Infinity) | 12/34 (35.3%) | 0/2 (0%) | ||||
| Diarrhea | 4/6 (66.7%) | 4/0 (Infinity) | 14/34 (41.2%) | 1/2 (50%) | ||||
| Dyspepsia | 0/6 (0%) | 0/0 (NaN) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Dysphagia | 1/6 (16.7%) | 1/0 (Infinity) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Hematemesis | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Ileus | 0/6 (0%) | 0/0 (NaN) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Mucositis oral | 5/6 (83.3%) | 5/0 (Infinity) | 21/34 (61.8%) | 0/2 (0%) | ||||
| Nausea | 5/6 (83.3%) | 5/0 (Infinity) | 18/34 (52.9%) | 1/2 (50%) | ||||
| Oral pain | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Perirectal fistula | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Rectal pain | 1/6 (16.7%) | 1/0 (Infinity) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Small bowel obstruction | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Toothache | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Vomiting | 3/6 (50%) | 3/0 (Infinity) | 17/34 (50%) | 1/2 (50%) | ||||
| General disorders | ||||||||
| Chills | 3/6 (50%) | 3/0 (Infinity) | 10/34 (29.4%) | 0/2 (0%) | ||||
| Edema face | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Edema limbs | 5/6 (83.3%) | 5/0 (Infinity) | 16/34 (47.1%) | 0/2 (0%) | ||||
| Fatigue | 4/6 (66.7%) | 4/0 (Infinity) | 15/34 (44.1%) | 0/2 (0%) | ||||
| Fever | 0/6 (0%) | 0/0 (NaN) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Hypothermia | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Infusion related reaction | 1/6 (16.7%) | 1/0 (Infinity) | 3/34 (8.8%) | 0/2 (0%) | ||||
| Malaise | 0/6 (0%) | 0/0 (NaN) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Non-cardiac chest pain | 1/6 (16.7%) | 1/0 (Infinity) | 2/34 (5.9%) | 1/2 (50%) | ||||
| Pain | 0/6 (0%) | 0/0 (NaN) | 7/34 (20.6%) | 0/2 (0%) | ||||
| Pain at G-tube insertion site | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Rigors | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatic abscess | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Infections and infestations | ||||||||
| Bacteremia-Bacillus cereus | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Bacteremia-Enterococcus faecium/Coagulase negative staphylococcus | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Bacteremia-Escherichia coli/Enterobacter cloacae | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Bacteremia-Escherichia coli/pseudomonas aeruginosa | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Bacteremia-Escherichia coli/streptococcus salvarius | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Bacteremia-MRSE | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Bacteremia-Staphylococcus epidermidis | 1/6 (16.7%) | 1/0 (Infinity) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Bacteremia-Streptococcus mitis | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Bacteremia-VRE | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Bone infection | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Catheter related infection | 2/6 (33.3%) | 2/0 (Infinity) | 3/34 (8.8%) | 0/2 (0%) | ||||
| Clostridium-difficile | 0/6 (0%) | 0/0 (NaN) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Endocarditis infective | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Eye infection | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Folliculitis | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Fungemia-Candida parapsilosis disseminated | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| HSV positive lip lesion | 0/6 (0%) | 0/0 (NaN) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Infectious hepatic lesions secondary to colitis | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Lung infection | 1/6 (16.7%) | 1/0 (Infinity) | 6/34 (17.6%) | 0/2 (0%) | ||||
| Meningitis | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Oral thrush | 2/6 (33.3%) | 2/0 (Infinity) | 4/34 (11.8%) | 0/2 (0%) | ||||
| Parotitis infectious | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Sepsis | 1/6 (16.7%) | 1/0 (Infinity) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Sinusitis | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Skin infection | 1/6 (16.7%) | 1/0 (Infinity) | 10/34 (29.4%) | 0/2 (0%) | ||||
| Upper respiratory infection | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Urinary tract infection | 1/6 (16.7%) | 1/0 (Infinity) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Bleeding at bone marrow biopsy site | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Bruising | 2/6 (33.3%) | 2/0 (Infinity) | 3/34 (8.8%) | 0/2 (0%) | ||||
| Fall | 1/6 (16.7%) | 1/0 (Infinity) | 5/34 (14.7%) | 0/2 (0%) | ||||
| Investigations | ||||||||
| Activated partial thromboplastin time prolonged | 1/6 (16.7%) | 1/0 (Infinity) | 6/34 (17.6%) | 0/2 (0%) | ||||
| Alanine aminotransferase increased | 6/6 (100%) | 6/0 (Infinity) | 17/34 (50%) | 0/2 (0%) | ||||
| Alkaline phosphatase increased | 3/6 (50%) | 3/0 (Infinity) | 19/34 (55.9%) | 0/2 (0%) | ||||
| Aspartate aminotransferase increased | 5/6 (83.3%) | 5/0 (Infinity) | 20/34 (58.8%) | 1/2 (50%) | ||||
| Blood bilirubin increased | 2/6 (33.3%) | 2/0 (Infinity) | 17/34 (50%) | 0/2 (0%) | ||||
| Creatinine increased | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Ejection fraction decreased | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Electrocardiogram QT corrected interval prolonged | 1/6 (16.7%) | 1/0 (Infinity) | 3/34 (8.8%) | 0/2 (0%) | ||||
| INR increased | 3/6 (50%) | 3/0 (Infinity) | 20/34 (58.8%) | 0/2 (0%) | ||||
| Lymphocyte count decreased | 5/6 (83.3%) | 5/0 (Infinity) | 32/34 (94.1%) | 0/2 (0%) | ||||
| Neutrophil count decreased | 1/6 (16.7%) | 1/0 (Infinity) | 21/34 (61.8%) | 2/2 (100%) | ||||
| Platelet count decreased | 3/6 (50%) | 3/0 (Infinity) | 22/34 (64.7%) | 2/2 (100%) | ||||
| Weight gain | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Weight loss | 5/6 (83.3%) | 5/0 (Infinity) | 17/34 (50%) | 0/2 (0%) | ||||
| White blood cell decreased | 3/6 (50%) | 3/0 (Infinity) | 28/34 (82.4%) | 2/2 (100%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Anorexia | 2/6 (33.3%) | 2/0 (Infinity) | 3/34 (8.8%) | 0/2 (0%) | ||||
| Dehydration | 0/6 (0%) | 0/0 (NaN) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Hypercalcemia | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Hyperglycemia | 1/6 (16.7%) | 1/0 (Infinity) | 11/34 (32.4%) | 0/2 (0%) | ||||
| Hyperkalemia | 1/6 (16.7%) | 1/0 (Infinity) | 14/34 (41.2%) | 1/2 (50%) | ||||
| Hypermagnesemia | 4/6 (66.7%) | 4/0 (Infinity) | 14/34 (41.2%) | 0/2 (0%) | ||||
| Hypernatremia | 1/6 (16.7%) | 1/0 (Infinity) | 6/34 (17.6%) | 0/2 (0%) | ||||
| Hypoalbuminemia | 5/6 (83.3%) | 5/0 (Infinity) | 21/34 (61.8%) | 0/2 (0%) | ||||
| Hypocalcemia | 3/6 (50%) | 3/0 (Infinity) | 31/34 (91.2%) | 0/2 (0%) | ||||
| Hypoglycemia | 1/6 (16.7%) | 1/0 (Infinity) | 5/34 (14.7%) | 0/2 (0%) | ||||
| Hypokalemia | 4/6 (66.7%) | 4/0 (Infinity) | 20/34 (58.8%) | 0/2 (0%) | ||||
| Hypomagnesemia | 0/6 (0%) | 0/0 (NaN) | 5/34 (14.7%) | 0/2 (0%) | ||||
| Hyponatremia | 6/6 (100%) | 6/0 (Infinity) | 33/34 (97.1%) | 1/2 (50%) | ||||
| Hypophosphatemia | 2/6 (33.3%) | 2/0 (Infinity) | 30/34 (88.2%) | 0/2 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Age indeterminant spinal stress fracture | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Back pain | 1/6 (16.7%) | 1/0 (Infinity) | 4/34 (11.8%) | 0/2 (0%) | ||||
| Bone pain | 0/6 (0%) | 0/0 (NaN) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Generalized muscle weakness | 2/6 (33.3%) | 2/0 (Infinity) | 5/34 (14.7%) | 0/2 (0%) | ||||
| Jaw pain | 2/6 (33.3%) | 2/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Joint effusion | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Pain in extremity | 1/6 (16.7%) | 1/0 (Infinity) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Worsening pain-hip/knees/legs | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 1/6 (16.7%) | 1/0 (Infinity) | 6/34 (17.6%) | 1/2 (50%) | ||||
| Encephalopathy | 1/6 (16.7%) | 1/0 (Infinity) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Headache | 2/6 (33.3%) | 2/0 (Infinity) | 6/34 (17.6%) | 0/2 (0%) | ||||
| Lethargy | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Paresthesia | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Peripheral sensory neuropathy | 0/6 (0%) | 0/0 (NaN) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Presyncope | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Reversible posterior leukoencephalopathy syndrome | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Somnolence | 0/6 (0%) | 0/0 (NaN) | 6/34 (17.6%) | 0/2 (0%) | ||||
| Syncope | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Psychiatric disorders | ||||||||
| Altered mental status | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Anxiety | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Confusion | 0/6 (0%) | 0/0 (NaN) | 8/34 (23.5%) | 0/2 (0%) | ||||
| Delirium | 2/6 (33.3%) | 2/0 (Infinity) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Depression | 1/6 (16.7%) | 1/0 (Infinity) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Hallucinations | 0/6 (0%) | 0/0 (NaN) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Insomnia | 1/6 (16.7%) | 1/0 (Infinity) | 4/34 (11.8%) | 0/2 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 2/6 (33.3%) | 2/0 (Infinity) | 5/34 (14.7%) | 0/2 (0%) | ||||
| Bladder spasm | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Hematuria | 2/6 (33.3%) | 2/0 (Infinity) | 13/34 (38.2%) | 0/2 (0%) | ||||
| Proteinuria | 2/6 (33.3%) | 2/0 (Infinity) | 18/34 (52.9%) | 0/2 (0%) | ||||
| Urinary incontinence | 0/6 (0%) | 0/0 (NaN) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Urinary urgency | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Urine output decreased | 0/6 (0%) | 0/0 (NaN) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Genital edema | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Aspiration | 0/6 (0%) | 0/0 (NaN) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Atelectasis | 2/6 (33.3%) | 2/0 (Infinity) | 7/34 (20.6%) | 0/2 (0%) | ||||
| Cough | 2/6 (33.3%) | 2/0 (Infinity) | 4/34 (11.8%) | 0/2 (0%) | ||||
| Dyspnea | 1/6 (16.7%) | 1/0 (Infinity) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Epistaxis | 0/6 (0%) | 0/0 (NaN) | 6/34 (17.6%) | 0/2 (0%) | ||||
| Hemoptysis | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Hypoxia | 1/6 (16.7%) | 1/0 (Infinity) | 7/34 (20.6%) | 0/2 (0%) | ||||
| Nasal congestion | 0/6 (0%) | 0/0 (NaN) | 5/34 (14.7%) | 0/2 (0%) | ||||
| Pleural effusion | 2/6 (33.3%) | 2/0 (Infinity) | 8/34 (23.5%) | 0/2 (0%) | ||||
| Pleuritic pain | 1/6 (16.7%) | 1/0 (Infinity) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Pulmonary edema | 0/6 (0%) | 0/0 (NaN) | 4/34 (11.8%) | 0/2 (0%) | ||||
| Respiratory failure | 1/6 (16.7%) | 1/0 (Infinity) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Sore throat | 0/6 (0%) | 0/0 (NaN) | 2/34 (5.9%) | 1/2 (50%) | ||||
| Wheezing | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 1/6 (16.7%) | 1/0 (Infinity) | 6/34 (17.6%) | 0/2 (0%) | ||||
| Lipoma | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Nasal lesion | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Night sweats | 0/6 (0%) | 0/0 (NaN) | 3/34 (8.8%) | 0/2 (0%) | ||||
| Perianal lesion | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Purpura | 1/6 (16.7%) | 1/0 (Infinity) | 0/34 (0%) | 0/2 (0%) | ||||
| Rash maculo-papular | 1/6 (16.7%) | 1/0 (Infinity) | 6/34 (17.6%) | 0/2 (0%) | ||||
| Skin abrasion | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Skin ulceration | 1/6 (16.7%) | 1/0 (Infinity) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Sweet's syndrome | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Vascular disorders | ||||||||
| Hematoma | 1/6 (16.7%) | 1/0 (Infinity) | 2/34 (5.9%) | 0/2 (0%) | ||||
| Hypertension | 1/6 (16.7%) | 1/0 (Infinity) | 4/34 (11.8%) | 0/2 (0%) | ||||
| Hypotension | 1/6 (16.7%) | 1/0 (Infinity) | 7/34 (20.6%) | 0/2 (0%) | ||||
| Phlebitis | 0/6 (0%) | 0/0 (NaN) | 1/34 (2.9%) | 0/2 (0%) | ||||
| Thromboembolic event | 1/6 (16.7%) | 1/0 (Infinity) | 2/34 (5.9%) | 0/2 (0%) | ||||
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Geoffrey Uy, M.D. |
|---|---|
| Organization | Washington University School of Medicine |
| Phone | 314-747-8439 |
| guy@wustl.edu |
- 201505084