Pomalidomide in Combination With High Dose Dexamethasone and Oral Cyclophosphamide
Study Details
Study Description
Brief Summary
The main purpose of this study is to see whether pomalidomide can help people with myeloma. Researchers also want to find out if pomalidomide is safe and tolerable.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
There are two parts to this study:
-
Phase 1: To determine a safe dose of the medication cyclophosphamide in combination with pomalidomide and dexamethasone.
-
Phase 2: To see the difference in effectiveness of pomalidomide in combination with high dose dexamethasone with or without cyclophosphamide for the treatment of participants who have myeloma, which has relapsed to or become refractory (not responding) to prior treatment.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A: Dose Escalation of Cyclophosphamide Phase I: Pomalidomide, high dose dexamethasone and oral cyclophosphamide: Pomalidomide 4 mg by mouth (PO) days 1-21 of a 28 days cycle. Dexamethasone 40* mg PO days 1- 4, 15-18 of a 28 days cycle for the first 4 cycles and subsequently 40 mg PO Days 1,8,15, 22. *Participants who were >75 years of age or those who were known to be intolerant to 40 mg weekly dexamethasone received 20 mg dexamethasone on the same schedule. Dose Escalation of Cyclophosphamide, orallly (PO) days 1, 8, 15 as follows: Level 1: 300 mg; Level 2: 400 mg; Level 3: 500 mg. Aspirin 81 mg PO daily (unless the participants had contraindications or were receiving other form of anticoagulation for other indications). |
Drug: Pomalidomide
Pomalidomide at 4 mg by mouth (PO) as outlined in the treatment arms.
Other Names:
Drug: Dexamethasone
Dexamethasone at 40 mg (20 mg) PO as outlined in the treatment arms.
Other Names:
Drug: Cyclophosphamide
The dose escalation uses a standard "3x3" design: Ex: If none of the first 3 participants have a DLT, enter 3 participants at the next higher dose level. Once the maximum tolerated dose (MTD) of oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone was determined, investigators proceeded with the second phase of the trial, a randomized phase II study comparing pomalidomide and dexamethasone with pomalidomide, dexamethasone and oral weekly cyclophosphamide delivered at the MTD determined in the phase I study.
Other Names:
|
| Active Comparator: B: Pomalidomide and Dexamethasone Randomized Phase II - Pomalidomide high dose dexamethasone: Pomalidomide 4 mg PO days 1-21 of a 28 days cycle. Dexamethasone 40* mg PO Days 1,8,15, 22. *Participants who were >75 years of age or those who were known to be intolerant to 40 mg weekly dexamethasone received 20 mg dexamethasone on the same schedule. Aspirin 81 mg PO daily (unless the participants had contraindications or were receiving other form of anticoagulation for other indications). |
Drug: Pomalidomide
Pomalidomide at 4 mg by mouth (PO) as outlined in the treatment arms.
Other Names:
Drug: Dexamethasone
Dexamethasone at 40 mg (20 mg) PO as outlined in the treatment arms.
Other Names:
|
| Active Comparator: C: Pomalidomide/Dexamethasone/Cyclophosphamide Randomized Phase II - Pomalidomide high dose dexamethasone and oral cyclophosphamide: Pomalidomide 4 mg PO days 1-21 of a 28 days cycle. Dexamethasone 40* mg PO days 1- 4, 15-18 of a 28 days cycle for the first 4 cycles and subsequently 40 mg PO Days 1,8,15, 22. *Participants who were >75 years of age or those who were known to be intolerant to 40 mg weekly dexamethasone received 20 mg dexamethasone on the same schedule. Cyclophosphamide 400 mg PO days 1, 8, 15. Aspirin 81 mg PO daily (unless the participants had contraindications or were receiving other form of anticoagulation for other indications). |
Drug: Pomalidomide
Pomalidomide at 4 mg by mouth (PO) as outlined in the treatment arms.
Other Names:
Drug: Dexamethasone
Dexamethasone at 40 mg (20 mg) PO as outlined in the treatment arms.
Other Names:
Drug: Cyclophosphamide
The dose escalation uses a standard "3x3" design: Ex: If none of the first 3 participants have a DLT, enter 3 participants at the next higher dose level. Once the maximum tolerated dose (MTD) of oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone was determined, investigators proceeded with the second phase of the trial, a randomized phase II study comparing pomalidomide and dexamethasone with pomalidomide, dexamethasone and oral weekly cyclophosphamide delivered at the MTD determined in the phase I study.
Other Names:
|
| Other: D: Crossover Crossover from Arm B to Arm D. Participants who experienced progressive disease in arm B were allowed to crossover to arm D at the discretion of the treating physician, in which case oral weekly Cyclophosphamide (400 mg orally on days 1, 8, and 15) was added to their tolerated dose of pomalidomide and dexamethasone. |
Drug: Pomalidomide
Pomalidomide at 4 mg by mouth (PO) as outlined in the treatment arms.
Other Names:
Drug: Dexamethasone
Dexamethasone at 40 mg (20 mg) PO as outlined in the treatment arms.
Other Names:
Drug: Cyclophosphamide
The dose escalation uses a standard "3x3" design: Ex: If none of the first 3 participants have a DLT, enter 3 participants at the next higher dose level. Once the maximum tolerated dose (MTD) of oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone was determined, investigators proceeded with the second phase of the trial, a randomized phase II study comparing pomalidomide and dexamethasone with pomalidomide, dexamethasone and oral weekly cyclophosphamide delivered at the MTD determined in the phase I study.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Phase I - Maximum Tolerated Dose (MTD) [28 Days]
The maximum tolerated dose of oral weekly cyclophosphamide in milligrams (mg), in combination with pomalidomide and dexamethasone. Dose Escalation of Cyclophosphamide, orallly (PO) days 1, 8, 15 as follows: Level 1: 300 mg; Level 2: 400 mg; Level 3: 500 mg. The period for assessment of Dose Limiting Toxicity (DLT) is the first cycle (28 days). The following toxicities will be considered dose limiting if encountered only in the phase I portion of the study: Febrile neutropenia; Grade 3 or 4 non-hematologic toxicity related to treatment with pomalidomide or cyclophosphamide; Participants must have received optimal symptomatic treatment for Grade 3 or 4 nausea, vomiting, or diarrhea to be considered a DLT; Grade 4 transaminitis; Grade 3 transaminitis must be present for ≥ 7 days to be considered a DLT; Grade 4 thrombocytopenia for 7 or more days; Grade 4 neutropenia for 7 or more days.
- Phase II - Overall Response Rate (ORR) [36 Months]
Overall response, Minimal Remission (MR) or better per treatment arm, using the uniform response criteria by the International Myeloma Working Group (IMWG) of pomalidomide in combination with high dose dexamethasone with or without cyclophosphamide in participants with relapsed and refractory myeloma. In addition, Minimal response was incorporated in those response criteria as this is a valid endpoint in patients with relapsed or refractory myeloma. MR: 25-49% reduction in serum paraprotein and a 50-89% reduction in urine light chain excretion; A 25-49% reduction in the size of soft tissue plasmacytoma must be demonstrated is applicable.
Secondary Outcome Measures
- Phase II - Median Progression Free Survival (PFS) [36 Months]
Progression free survival per treatment arm. Progressive Disease (PD) requires one of the following, increase of greater than or equal to 25% from baseline in: Serum M-component; Urine M-component; The difference between involved and uninvolved sFLC levels; The size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia.
- Phase II - Median Overall Survival (OS) [36 Months]
Overall survival per treatment arm. Overall survival is defined as the time from start of treatment to death of any cause.
- Phase II - Occurrence of Possibly Related Adverse Events (AEs) [Up to 48 Months]
Phase II: Participants with Grade 3 or 4 adverse events at least possibly related to the study treatment in 5% of participants in the Phase 2 portion, by AE category, assessed by the National Cancer Institute Common Terminology Criteria (NCI CTC) version 4.0.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participants must have relapsed or refractory multiple myeloma. Refractory disease is defined as patients who experience disease progression on active therapy or within 60 days after the discontinuation of therapy. Relapsed disease is defined as achievement of at least a partial response followed by disease progression after 60 days of discontinuing active therapy.
-
Must have measurable disease as assessed by one of the following criteria: Serum monoclonal protein ≥ 0.5 g/dL by protein electrophoresis; >200 mg of monoclonal protein in the urine on 24 hour electrophoresis; Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
-
Must have received at least 2 prior therapies to include prior immunomodulatory drug (lenalidomide) and the patient must be refractory to lenalidomide (defined as progressive disease during active therapy or within 60 days of discontinuation of therapy). All previous cancer chemotherapy (bisphosphonates are not included), including surgery, must have been discontinued ≥2 weeks prior to first dose of study drug. Prior radiotherapy must have been completed > 2 weeks prior to the start of study drug unless the radiation field would not impact marrow reserve in the opinion of the investigator.
-
Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%
-
Must have acceptable organ function: total bilirubin less than 1.5 mg/dL; aspartic transaminase (AST)/alanine transaminase (ALT) ≤2.5 X institutional upper limit of normal (ULN); serum creatinine < 3mg/dL
-
Must have adequate hematologic function as evidenced by the following:
-
For the Phase I study: Absolute neutrophil count (ANC) ≥ 1000 per mm³; Platelet count ≥ 50,000 per mm³.
-
For the Phase II portion, patients with greater than 50% bone marrow plasmacytosis will be allowed to enter the trial if the platelet count is greater than 30,000 per mm³ and regardless of baseline absolute neutrophil count if it is felt to be related to active myeloma and if in the opinion of the investigator, growth factor support can result in improvement in the neutrophil count to greater than 1000 per mm³ (growth factor can be used during screening).
-
Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy.
-
Ability to understand and the willingness to sign a written informed consent document
-
Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid (ASA) may use warfarin or low molecular weight heparin).
-
All study participants must be registered into the mandatory POMALYST REMS™ program, and be willing and able to comply with the requirements of the POMALYST REMS™ program.
Exclusion Criteria:
-
Patients who have had chemotherapy or radiotherapy within 2 weeks (see Inclusion Criteria above) or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier (except for neuropathy).
-
Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form
-
Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. Use of any other experimental drug or therapy within 28 days of baseline.
-
Known hypersensitivity to thalidomide or lenalidomide
-
The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, pomalidomide or similar drugs
-
Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A, B or C
-
May not be receiving any other investigational agents
-
Pregnant or breast feeding females (Lactating females must agree not to breast feed while taking pomalidomide).
-
Patients with prior pomalidomide therapy (greater than 1 cycle) are excluded.
-
Another active malignancy requiring treatment within the next 12 months, with the exception of basal cell skin cancer, in situ cervical cancer, in situ breast cancer and asymptomatic prostate cancer
-
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (except simple urinary tract or upper respiratory tract infection), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
-
Inability to comply with the protocol requirements or participation in any other clinical study
-
Corticosteroid therapies of >20 mg/day prednisone, >4 mg/day dexamethasone, >80 mg/day hydrocortisone, or equivalent
-
Allogeneic stem cell/bone marrow transplant within 12 months of first dose of study drug or active graft versus host disease
-
Patients with existing peripheral neuropathy grade >2
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California San Francisco | San Francisco | California | United States | 94143 |
| 2 | H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | United States | 33612 |
| 3 | Mount Sinai School of Medicine, The Tisch Cancer Institute | New York | New York | United States | 10029-6574 |
Sponsors and Collaborators
- H. Lee Moffitt Cancer Center and Research Institute
- Celgene
Investigators
- Principal Investigator: Rachid Baz, M.D., H. Lee Moffitt Cancer and Research Institute
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- MCC-16705
- PO-MM-PI-0039
Study Results
Participant Flow
| Recruitment Details | Between December 2011 and March 2014, participants were enrolled at: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | A: Dose Escalation of Cyclophosphamide | B: Pomalidomide and Dexamethasone | C: Pomalidomide, Dexamethasone, Cyclophosphamide |
|---|---|---|---|
| Arm/Group Description | Phase I: Pomalidomide, high dose dexamethasone and oral cyclophosphamide. | Phase II: Pomalidomide and high dose dexamethasone. Arm D participants may be referenced separately in some Outcome Measures. | Phase II: Pomalidomide high dose dexamethasone and oral cyclophosphamide. |
| Period Title: Overall Study | |||
| STARTED | 10 | 36 | 34 |
| COMPLETED | 10 | 35 | 33 |
| NOT COMPLETED | 0 | 1 | 1 |
Baseline Characteristics
| Arm/Group Title | A: Dose Escalation of Cyclophosphamide | B: Pomalidomide and Dexamethasone | C: Pomalidomide, Dexamethasone, Cyclophosphamide | Total |
|---|---|---|---|---|
| Arm/Group Description | Phase I: Pomalidomide, high dose dexamethasone and oral cyclophosphamide. | Phase II: Pomalidomide and high dose dexamethasone. Crossover Arm D is a part of Arm B. Arm D was opened later to accommodate requested transfers from Arm B. Participants who experienced progressive disease in arm B were allowed to crossover to arm D at the discretion of the treating physician. Arm D participants may be referenced separately in some Outcome Measures. | Phase II: Pomalidomide high dose dexamethasone and oral cyclophosphamide. | Total of all reporting groups |
| Overall Participants | 10 | 36 | 34 | 80 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
3
30%
|
19
52.8%
|
17
50%
|
39
48.8%
|
| >=65 years |
7
70%
|
17
47.2%
|
17
50%
|
41
51.3%
|
| Age (years) [Mean (Full Range) ] | ||||
| Mean (Full Range) [years] |
69
|
64
|
62
|
63
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
3
30%
|
13
36.1%
|
16
47.1%
|
32
40%
|
| Male |
7
70%
|
23
63.9%
|
18
52.9%
|
48
60%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
10
100%
|
36
100%
|
34
100%
|
80
100%
|
Outcome Measures
| Title | Phase I - Maximum Tolerated Dose (MTD) |
|---|---|
| Description | The maximum tolerated dose of oral weekly cyclophosphamide in milligrams (mg), in combination with pomalidomide and dexamethasone. Dose Escalation of Cyclophosphamide, orallly (PO) days 1, 8, 15 as follows: Level 1: 300 mg; Level 2: 400 mg; Level 3: 500 mg. The period for assessment of Dose Limiting Toxicity (DLT) is the first cycle (28 days). The following toxicities will be considered dose limiting if encountered only in the phase I portion of the study: Febrile neutropenia; Grade 3 or 4 non-hematologic toxicity related to treatment with pomalidomide or cyclophosphamide; Participants must have received optimal symptomatic treatment for Grade 3 or 4 nausea, vomiting, or diarrhea to be considered a DLT; Grade 4 transaminitis; Grade 3 transaminitis must be present for ≥ 7 days to be considered a DLT; Grade 4 thrombocytopenia for 7 or more days; Grade 4 neutropenia for 7 or more days. |
| Time Frame | 28 Days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Phase I Participants. |
| Arm/Group Title | A: Dose Escalation of Cyclophosphamide |
|---|---|
| Arm/Group Description | Phase I: Pomalidomide, high dose dexamethasone and oral cyclophosphamide. |
| Measure Participants | 10 |
| Number [mg] |
400
|
| Title | Phase II - Overall Response Rate (ORR) |
|---|---|
| Description | Overall response, Minimal Remission (MR) or better per treatment arm, using the uniform response criteria by the International Myeloma Working Group (IMWG) of pomalidomide in combination with high dose dexamethasone with or without cyclophosphamide in participants with relapsed and refractory myeloma. In addition, Minimal response was incorporated in those response criteria as this is a valid endpoint in patients with relapsed or refractory myeloma. MR: 25-49% reduction in serum paraprotein and a 50-89% reduction in urine light chain excretion; A 25-49% reduction in the size of soft tissue plasmacytoma must be demonstrated is applicable. |
| Time Frame | 36 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Phase II Participants. |
| Arm/Group Title | B: Pomalidomide and Dexamethasone | C: Pomalidomide, Dexamethasone, Cyclophosphamide |
|---|---|---|
| Arm/Group Description | Phase II: Pomalidomide and high dose dexamethasone. Crossover Arm D is a part of Arm B. Arm D was opened later to accommodate requested transfers from Arm B. Participants who experienced progressive disease in arm B were allowed to crossover to arm D at the discretion of the treating physician. Arm D participants may be referenced separately in some Outcome Measures. | Phase II: Pomalidomide high dose dexamethasone and oral cyclophosphamide. |
| Measure Participants | 36 | 34 |
| Number (95% Confidence Interval) [percentage of participants] |
38.9
389%
|
64.7
179.7%
|
| Title | Phase II - Median Progression Free Survival (PFS) |
|---|---|
| Description | Progression free survival per treatment arm. Progressive Disease (PD) requires one of the following, increase of greater than or equal to 25% from baseline in: Serum M-component; Urine M-component; The difference between involved and uninvolved sFLC levels; The size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia. |
| Time Frame | 36 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Phase II Participants. |
| Arm/Group Title | B: Pomalidomide and Dexamethasone | C: Pomalidomide, Dexamethasone, Cyclophosphamide |
|---|---|---|
| Arm/Group Description | Phase II: Pomalidomide and high dose dexamethasone. Crossover Arm D is a part of Arm B. Arm D was opened later to accommodate requested transfers from Arm B. Participants who experienced progressive disease in arm B were allowed to crossover to arm D at the discretion of the treating physician. Arm D participants may be referenced separately in some Outcome Measures. | Phase II: Pomalidomide high dose dexamethasone and oral cyclophosphamide. |
| Measure Participants | 36 | 34 |
| Median (95% Confidence Interval) [months] |
4.4
|
9.5
|
| Title | Phase II - Median Overall Survival (OS) |
|---|---|
| Description | Overall survival per treatment arm. Overall survival is defined as the time from start of treatment to death of any cause. |
| Time Frame | 36 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants assigned to Arm B and Arm C. |
| Arm/Group Title | B: Pomalidomide and Dexamethasone | C: Pomalidomide, Dexamethasone, Cyclophosphamide |
|---|---|---|
| Arm/Group Description | Phase II: Pomalidomide and high dose dexamethasone. Crossover Arm D is a part of Arm B. Arm D was opened later to accommodate requested transfers from Arm B. Participants who experienced progressive disease in arm B were allowed to crossover to arm D at the discretion of the treating physician. Arm D participants may be referenced separately in some Outcome Measures. | Phase II: Pomalidomide high dose dexamethasone and oral cyclophosphamide. |
| Measure Participants | 36 | 34 |
| Median (95% Confidence Interval) [months] |
16.8
|
NA
|
| Title | Phase II - Occurrence of Possibly Related Adverse Events (AEs) |
|---|---|
| Description | Phase II: Participants with Grade 3 or 4 adverse events at least possibly related to the study treatment in 5% of participants in the Phase 2 portion, by AE category, assessed by the National Cancer Institute Common Terminology Criteria (NCI CTC) version 4.0. |
| Time Frame | Up to 48 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Phase II Participants who completed allocated intervention. |
| Arm/Group Title | B: Pomalidomide and Dexamethasone | C: Pomalidomide, Dexamethasone, Cyclophosphamide | D: Crossover Arm |
|---|---|---|---|
| Arm/Group Description | Phase II: Pomalidomide and high dose dexamethasone. Crossover Arm D is a part of Arm B. Arm D was opened later to accommodate requested transfers from Arm B. Participants who experienced progressive disease in arm B were allowed to crossover to arm D at the discretion of the treating physician. Arm D participants may be referenced separately in some Outcome Measures. | Phase II: Pomalidomide high dose dexamethasone and oral cyclophosphamide. | Phase II: Participants who crossed over from Arm B to Arm D. Crossover Arm D is a part of Arm B. Arm D was opened later to accommodate requested transfers from Arm B. Participants who experienced progressive disease in arm B were allowed to crossover to arm D at the discretion of the treating physician. |
| Measure Participants | 35 | 33 | 17 |
| Anemia |
11.4
114%
|
24.2
67.2%
|
5.9
17.4%
|
| Febrile neutropenia |
11.4
114%
|
12.1
33.6%
|
0
0%
|
| Fatigue |
8.6
86%
|
1.21
3.4%
|
0
0%
|
| Flu-like symptoms |
0
0%
|
0
0%
|
5.9
17.4%
|
| Lung infection |
11.4
114%
|
9.1
25.3%
|
5.9
17.4%
|
| Sepsis |
0
0%
|
9.1
25.3%
|
0
0%
|
| Upper respiratory infection |
0
0%
|
6.1
16.9%
|
0
0%
|
| Lymphodemia |
11.4
114%
|
9.1
25.3%
|
11.8
34.7%
|
| Neutropenia |
31.4
314%
|
51.5
143.1%
|
23.5
69.1%
|
| Thrombocytopenia |
5.7
57%
|
15.2
42.2%
|
0
0%
|
| Leukopenia |
14.3
143%
|
12.1
33.6%
|
5.9
17.4%
|
| Hyperglycemia |
0
0%
|
6.1
16.9%
|
0
0%
|
| Hyponatremia |
0
0%
|
6.1
16.9%
|
0
0%
|
| Hypophosphatemia |
0
0%
|
0
0%
|
5.9
17.4%
|
| Hypoxia |
0
0%
|
0
0%
|
5.9
17.4%
|
| Confusion |
0
0%
|
6.1
16.9%
|
0
0%
|
| Pneumonitis |
0
0%
|
9.1
25.3%
|
0
0%
|
| Thromboembolic event |
0
0%
|
6.1
16.9%
|
0
0%
|
Adverse Events
| Time Frame | 4 years, 1 month | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All participants assigned to Arms A, B, C, plus Arm D group of participants formerly in Arm B (Arm B occurrences listed under B, Arm D occurrences listed under D). | |||||||
| Arm/Group Title | A: Dose Escalation of Cyclophosphamide | B: Pomalidomide and Dexamethasone | C: Pomalidomide, Dexamethasone, Cyclophosphamide | D: Crossover Arm | ||||
| Arm/Group Description | Phase I: Pomalidomide, high dose dexamethasone and oral cyclophosphamide. | Phase II: Pomalidomide and high dose dexamethasone. Crossover Arm D is a part of Arm B. Arm D was opened later to accommodate requested transfers from Arm B. Participants who experienced progressive disease in arm B were allowed to crossover to arm D at the discretion of the treating physician. Arm D participants may be referenced separately in some Outcome Measures. | Phase II: Pomalidomide high dose dexamethasone and oral cyclophosphamide. | Phase II: Participants who crossed over from Arm B to Arm D. | ||||
All Cause Mortality |
||||||||
| A: Dose Escalation of Cyclophosphamide | B: Pomalidomide and Dexamethasone | C: Pomalidomide, Dexamethasone, Cyclophosphamide | D: Crossover Arm | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| A: Dose Escalation of Cyclophosphamide | B: Pomalidomide and Dexamethasone | C: Pomalidomide, Dexamethasone, Cyclophosphamide | D: Crossover Arm | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/10 (100%) | 11/36 (30.6%) | 19/34 (55.9%) | 9/17 (52.9%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anemia | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 3/34 (8.8%) | 3 | 0/17 (0%) | 0 |
| Febrile Neutropenia | 3/10 (30%) | 3 | 2/36 (5.6%) | 2 | 4/34 (11.8%) | 4 | 2/17 (11.8%) | 3 |
| Cardiac disorders | ||||||||
| Atrial fibrillation | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Cardiac disorders - Other | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Eye disorders | ||||||||
| Retinal vascular disorder | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Colitis | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Colonic hemorrhage | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Colonic obstruction | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Colonic perforation | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Gastrointestinal disorders, Other | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Rectal hemorrhage | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| General disorders | ||||||||
| Fatigue | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 1/17 (5.9%) | 1 |
| Fever | 0/10 (0%) | 0 | 2/36 (5.6%) | 3 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| General disorders - Other | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 2/17 (11.8%) | 2 |
| Non-cardiac chest pain | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Pain | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 1/17 (5.9%) | 1 |
| Infections and infestations | ||||||||
| Appendicitis | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Infections and infestations - Other | 1/10 (10%) | 1 | 2/36 (5.6%) | 2 | 4/34 (11.8%) | 4 | 0/17 (0%) | 0 |
| Lung infection | 1/10 (10%) | 1 | 4/36 (11.1%) | 4 | 3/34 (8.8%) | 4 | 3/17 (17.6%) | 3 |
| Sepsis | 2/10 (20%) | 2 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Sinusitis | 1/10 (10%) | 2 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Upper respiratory infection | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 2/34 (5.9%) | 2 | 0/17 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Fracture | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 1/17 (5.9%) | 1 |
| Investigations | ||||||||
| Creatinine increased | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Platelet count decreased | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 1/10 (10%) | 1 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Musculoskeletal and connective tissue disorders - Other | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Neoplasms benign, malignant and unspecified - Other | 1/10 (10%) | 1 | 2/36 (5.6%) | 2 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Treatment related secondary malignancy | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Nervous system disorders | ||||||||
| Dizziness | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Neuralgia | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Stroke | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Renal and urinary disorders - Other | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Adult respiratory distress syndrome | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 1/17 (5.9%) | 1 |
| Bronchial obstruction | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Bronchospasm | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Dyspnea | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Pneumonitis | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 1 | 2/17 (11.8%) | 2 |
| Wheezing | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 1/17 (5.9%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| Pruritus | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Surgical and medical procedures | ||||||||
| Surgical and medical procedures - Other | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Vascular disorders | ||||||||
| Hypotension | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Thromboembolic event | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| A: Dose Escalation of Cyclophosphamide | B: Pomalidomide and Dexamethasone | C: Pomalidomide, Dexamethasone, Cyclophosphamide | D: Crossover Arm | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/10 (100%) | 35/36 (97.2%) | 33/34 (97.1%) | 15/17 (88.2%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anemia | 2/10 (20%) | 2 | 15/36 (41.7%) | 21 | 17/34 (50%) | 54 | 6/17 (35.3%) | 10 |
| Febrile Neutropenia | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 2/34 (5.9%) | 3 | 0/17 (0%) | 0 |
| Blood and Lymphatic System Disorders - Other | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 2 | 0/17 (0%) | 0 |
| Spleen disorder | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Cardiac disorders | ||||||||
| Atrial fibrillation | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Sinus tachycardia | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 2/34 (5.9%) | 2 | 0/17 (0%) | 0 |
| Cardiac disorders - Other, specify | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Chest pain - cardiac | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Sinus bradycardia | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Ventricular arrhythmia | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||
| Ear and labyrinth disorders - Other, specify | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Vertigo | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Endocrine disorders | ||||||||
| Adrenal insufficiency | 0/10 (0%) | 0 | 3/36 (8.3%) | 3 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Endocrine disorders - Other, specify | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Hypothyroidism | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Eye disorders | ||||||||
| Eye disorders - Other, specify | 2/10 (20%) | 2 | 1/36 (2.8%) | 1 | 2/34 (5.9%) | 2 | 0/17 (0%) | 0 |
| Blurred vision | 0/10 (0%) | 0 | 4/36 (11.1%) | 4 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Cataract | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Dry eye | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Eye pain | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Conjunctivitis | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Flashing lights | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Vitreous hemorrhage | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Nausea | 3/10 (30%) | 5 | 6/36 (16.7%) | 7 | 10/34 (29.4%) | 15 | 1/17 (5.9%) | 1 |
| Diarrhea | 1/10 (10%) | 1 | 6/36 (16.7%) | 9 | 10/34 (29.4%) | 11 | 2/17 (11.8%) | 3 |
| Constipation | 0/10 (0%) | 0 | 8/36 (22.2%) | 9 | 6/34 (17.6%) | 7 | 1/17 (5.9%) | 1 |
| Vomiting | 3/10 (30%) | 3 | 4/36 (11.1%) | 5 | 3/34 (8.8%) | 3 | 2/17 (11.8%) | 2 |
| Gastrointestinal disorders - Other, specify | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 4/34 (11.8%) | 6 | 0/17 (0%) | 0 |
| Dyspepsia | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Gastroesophageal reflux disease | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 3/34 (8.8%) | 4 | 0/17 (0%) | 0 |
| Mucositis oral | 2/10 (20%) | 2 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Rectal hemorrhage | 2/10 (20%) | 2 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Colitis | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Abdominal pain | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Colonic obstruction | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Dental caries | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 2 | 0/17 (0%) | 0 |
| Esophagitis | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Gastric ulcer | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Hemorrhoids | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Oral hemorrhage | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Oral pain | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Stomach pain | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Toothache | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| General disorders | ||||||||
| Fatigue | 2/10 (20%) | 2 | 12/36 (33.3%) | 12 | 7/34 (20.6%) | 9 | 2/17 (11.8%) | 2 |
| Pain | 1/10 (10%) | 1 | 3/36 (8.3%) | 3 | 10/34 (29.4%) | 14 | 1/17 (5.9%) | 1 |
| Fever | 3/10 (30%) | 5 | 6/36 (16.7%) | 6 | 4/34 (11.8%) | 8 | 1/17 (5.9%) | 1 |
| Edema limbs | 0/10 (0%) | 0 | 4/36 (11.1%) | 5 | 6/34 (17.6%) | 7 | 1/17 (5.9%) | 1 |
| General disorders and administration site conditions - Other, specify | 0/10 (0%) | 0 | 2/36 (5.6%) | 3 | 7/34 (20.6%) | 12 | 2/17 (11.8%) | 2 |
| Chills | 2/10 (20%) | 2 | 3/36 (8.3%) | 3 | 1/34 (2.9%) | 1 | 1/17 (5.9%) | 1 |
| Flu like symptoms | 2/10 (20%) | 3 | 2/36 (5.6%) | 2 | 2/34 (5.9%) | 2 | 0/17 (0%) | 0 |
| Non-cardiac chest pain | 1/10 (10%) | 1 | 2/36 (5.6%) | 2 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Gait disturbance | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 1/17 (5.9%) | 1 |
| Irritability | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 2/34 (5.9%) | 2 | 0/17 (0%) | 0 |
| Edema trunk | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Localized edema | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Malaise | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Infections and infestations | ||||||||
| Lung infection | 1/10 (10%) | 2 | 3/36 (8.3%) | 4 | 5/34 (14.7%) | 7 | 3/17 (17.6%) | 3 |
| Infections and infestations - Other, specify | 0/10 (0%) | 0 | 5/36 (13.9%) | 6 | 3/34 (8.8%) | 4 | 0/17 (0%) | 0 |
| Upper respiratory infection | 1/10 (10%) | 1 | 5/36 (13.9%) | 8 | 5/34 (14.7%) | 10 | 1/17 (5.9%) | 1 |
| Sepsis | 4/10 (40%) | 5 | 1/36 (2.8%) | 1 | 5/34 (14.7%) | 5 | 0/17 (0%) | 0 |
| Skin infection | 1/10 (10%) | 1 | 2/36 (5.6%) | 2 | 3/34 (8.8%) | 4 | 0/17 (0%) | 0 |
| Urinary tract infection | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 3/34 (8.8%) | 3 | 1/17 (5.9%) | 1 |
| Bronchial infection | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 3/34 (8.8%) | 3 | 0/17 (0%) | 0 |
| Rhinitis infective | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Sinusitis | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Eye infection | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Papulopustular rash | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Rash pustular | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Small intestine infection | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Bruising | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Fall | 0/10 (0%) | 0 | 1/36 (2.8%) | 2 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Injury, poisoning and procedural complications - Other, specify | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 1/17 (5.9%) | 1 |
| Intraoperative renal injury | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Investigations | ||||||||
| Neutrophil count decreased | 6/10 (60%) | 10 | 16/36 (44.4%) | 36 | 20/34 (58.8%) | 76 | 8/17 (47.1%) | 18 |
| Platelet count decreased | 8/10 (80%) | 10 | 10/36 (27.8%) | 15 | 16/34 (47.1%) | 46 | 2/17 (11.8%) | 2 |
| White blood cell decreased | 2/10 (20%) | 3 | 7/36 (19.4%) | 13 | 8/34 (23.5%) | 52 | 4/17 (23.5%) | 15 |
| Lymphocyte count decreased | 0/10 (0%) | 0 | 4/36 (11.1%) | 20 | 4/34 (11.8%) | 24 | 3/17 (17.6%) | 15 |
| Weight gain | 0/10 (0%) | 0 | 3/36 (8.3%) | 4 | 4/34 (11.8%) | 5 | 0/17 (0%) | 0 |
| Aspartate aminotransferase increased | 1/10 (10%) | 1 | 3/36 (8.3%) | 3 | 2/34 (5.9%) | 2 | 1/17 (5.9%) | 2 |
| Alanine aminotransferase increased | 1/10 (10%) | 1 | 2/36 (5.6%) | 2 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Alkaline phosphatase increased | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 1 | 2/17 (11.8%) | 3 |
| Weight loss | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 3/34 (8.8%) | 3 | 0/17 (0%) | 0 |
| Creatinine increased | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 2 | 0/17 (0%) | 0 |
| Blood bilirubin increased | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Carbon monoxide diffusing capacity decreased | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Cardiac troponin I increased | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Cardiac troponin T increased | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Hyperglycemia | 3/10 (30%) | 3 | 5/36 (13.9%) | 5 | 6/34 (17.6%) | 7 | 0/17 (0%) | 0 |
| Dehydration | 1/10 (10%) | 1 | 3/36 (8.3%) | 3 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Hypomagnesemia | 0/10 (0%) | 0 | 2/36 (5.6%) | 4 | 4/34 (11.8%) | 4 | 2/17 (11.8%) | 2 |
| Hypoalbuminemia | 0/10 (0%) | 0 | 4/36 (11.1%) | 7 | 1/34 (2.9%) | 1 | 3/17 (17.6%) | 4 |
| Hypocalcemia | 0/10 (0%) | 0 | 4/36 (11.1%) | 5 | 2/34 (5.9%) | 2 | 1/17 (5.9%) | 3 |
| Hyponatremia | 0/10 (0%) | 0 | 3/36 (8.3%) | 3 | 3/34 (8.8%) | 3 | 0/17 (0%) | 0 |
| Anorexia | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 2/34 (5.9%) | 2 | 1/17 (5.9%) | 1 |
| Hyperkalemia | 1/10 (10%) | 1 | 1/36 (2.8%) | 1 | 3/34 (8.8%) | 3 | 0/17 (0%) | 0 |
| Hypokalemia | 0/10 (0%) | 0 | 3/36 (8.3%) | 3 | 2/34 (5.9%) | 4 | 0/17 (0%) | 0 |
| Hypercalcemia | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 0/34 (0%) | 0 | 1/17 (5.9%) | 1 |
| Hypophosphatemia | 0/10 (0%) | 0 | 3/36 (8.3%) | 7 | 0/34 (0%) | 0 | 1/17 (5.9%) | 3 |
| Hypernatremia | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Metabolism and nutrition disorders - Other, specify | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 1/17 (5.9%) | 1 |
| Hypoglycemia | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Iron overload | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Generalized muscle weakness | 0/10 (0%) | 0 | 6/36 (16.7%) | 7 | 3/34 (8.8%) | 3 | 2/17 (11.8%) | 2 |
| Pain in extremity | 3/10 (30%) | 3 | 5/36 (13.9%) | 5 | 2/34 (5.9%) | 3 | 1/17 (5.9%) | 2 |
| Musculoskeletal and connective tissue disorder - Other, specify | 0/10 (0%) | 0 | 6/36 (16.7%) | 6 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Bone pain | 2/10 (20%) | 2 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 1 | 1/17 (5.9%) | 2 |
| Back pain | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 2/34 (5.9%) | 2 | 0/17 (0%) | 0 |
| Chest wall pain | 0/10 (0%) | 0 | 1/36 (2.8%) | 2 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Flank pain | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 1/17 (5.9%) | 1 |
| Myalgia | 1/10 (10%) | 1 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Buttock pain | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Muscle weakness lower limb | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Neck pain | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Osteonecrosis of jaw | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 2 | 0/17 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Nervous system disorders | ||||||||
| Tremor | 0/10 (0%) | 0 | 7/36 (19.4%) | 8 | 5/34 (14.7%) | 5 | 3/17 (17.6%) | 3 |
| Dizziness | 2/10 (20%) | 2 | 2/36 (5.6%) | 2 | 5/34 (14.7%) | 7 | 3/17 (17.6%) | 3 |
| Peripheral sensory neuropathy | 0/10 (0%) | 0 | 4/36 (11.1%) | 5 | 4/34 (11.8%) | 5 | 2/17 (11.8%) | 2 |
| Headache | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 4/34 (11.8%) | 4 | 0/17 (0%) | 0 |
| Ataxia | 1/10 (10%) | 1 | 2/36 (5.6%) | 2 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Nervous system disorders - Other, specify | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 3/34 (8.8%) | 3 | 0/17 (0%) | 0 |
| Memory impairment | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 2/34 (5.9%) | 2 | 0/17 (0%) | 0 |
| Syncope | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 0/34 (0%) | 0 | 1/17 (5.9%) | 1 |
| Cognitive disturbance | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 2 | 0/17 (0%) | 0 |
| Presyncope | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 1/17 (5.9%) | 1 |
| Somnolence | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Dysgeusia | 0/10 (0%) | 0 | 1/36 (2.8%) | 3 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Paresthesia | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Peripheral motor neuropathy | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Insomnia | 2/10 (20%) | 2 | 4/36 (11.1%) | 4 | 2/34 (5.9%) | 4 | 1/17 (5.9%) | 1 |
| Confusion | 1/10 (10%) | 1 | 2/36 (5.6%) | 4 | 3/34 (8.8%) | 3 | 0/17 (0%) | 0 |
| Anxiety | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 3/34 (8.8%) | 5 | 1/17 (5.9%) | 1 |
| Psychiatric disorders - Other, specify | 0/10 (0%) | 0 | 1/36 (2.8%) | 2 | 3/34 (8.8%) | 3 | 0/17 (0%) | 0 |
| Depression | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 1 | 1/17 (5.9%) | 1 |
| Personality change | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Suicidal ideation | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Urinary frequency | 1/10 (10%) | 1 | 2/36 (5.6%) | 2 | 3/34 (8.8%) | 3 | 1/17 (5.9%) | 1 |
| Renal and urinary disorders - Other, specify | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 2/34 (5.9%) | 3 | 0/17 (0%) | 0 |
| Hematuria | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 1/34 (2.9%) | 2 | 0/17 (0%) | 0 |
| Urinary incontinence | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Urinary tract pain | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Pelvic pain | 0/10 (0%) | 0 | 2/36 (5.6%) | 3 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnea | 3/10 (30%) | 4 | 6/36 (16.7%) | 6 | 7/34 (20.6%) | 8 | 1/17 (5.9%) | 3 |
| Cough | 1/10 (10%) | 1 | 1/36 (2.8%) | 3 | 4/34 (11.8%) | 4 | 1/17 (5.9%) | 2 |
| Pneumonitis | 1/10 (10%) | 1 | 1/36 (2.8%) | 1 | 3/34 (8.8%) | 3 | 1/17 (5.9%) | 1 |
| Allergic rhinitis | 1/10 (10%) | 1 | 2/36 (5.6%) | 2 | 1/34 (2.9%) | 2 | 1/17 (5.9%) | 1 |
| Productive cough | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 3/34 (8.8%) | 3 | 1/17 (5.9%) | 1 |
| Epistaxis | 1/10 (10%) | 1 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Hoarseness | 1/10 (10%) | 1 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Nasal congestion | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders - Other, specify | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Sore throat | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Voice alteration | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Wheezing | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 1/17 (5.9%) | 1 |
| Hiccups | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 2 | 0/17 (0%) | 0 |
| Hypoxia | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 1/17 (5.9%) | 1 |
| Laryngeal inflammation | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Pleural effusion | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Pulmonary hypertension | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 1/17 (5.9%) | 1 |
| Respiratory failure | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Skin and subcutaneous tissue disorders - Other, specify | 3/10 (30%) | 3 | 2/36 (5.6%) | 2 | 6/34 (17.6%) | 8 | 0/17 (0%) | 0 |
| Pruritus | 2/10 (20%) | 2 | 4/36 (11.1%) | 5 | 3/34 (8.8%) | 3 | 0/17 (0%) | 0 |
| Rash acneiform | 1/10 (10%) | 1 | 5/36 (13.9%) | 5 | 3/34 (8.8%) | 3 | 0/17 (0%) | 0 |
| Dry skin | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 4/34 (11.8%) | 4 | 0/17 (0%) | 0 |
| Skin ulceration | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 3/34 (8.8%) | 3 | 0/17 (0%) | 0 |
| Hyperhidrosis | 0/10 (0%) | 0 | 2/36 (5.6%) | 2 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Rash maculo-papular | 1/10 (10%) | 1 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Skin induration | 2/10 (20%) | 2 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Alopecia | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Body odor | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Erythema multiforme | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Pain of skin | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 1/34 (2.9%) | 1 | 0/17 (0%) | 0 |
| Palmar-plantar erythrodysesthesia syndrome | 1/10 (10%) | 1 | 0/36 (0%) | 0 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Surgical and medical procedures | ||||||||
| Surgical and medical procedures - Other, specify | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 1/34 (2.9%) | 2 | 0/17 (0%) | 0 |
| Vascular disorders | ||||||||
| Thromboembolic event | 3/10 (30%) | 3 | 1/36 (2.8%) | 1 | 3/34 (8.8%) | 3 | 0/17 (0%) | 0 |
| Flushing | 1/10 (10%) | 1 | 1/36 (2.8%) | 1 | 3/34 (8.8%) | 3 | 0/17 (0%) | 0 |
| Hypotension | 1/10 (10%) | 1 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 0 |
| Vascular disorders - Other, specify | 0/10 (0%) | 0 | 0/36 (0%) | 0 | 2/34 (5.9%) | 2 | 0/17 (0%) | 0 |
| Hypertension | 0/10 (0%) | 0 | 1/36 (2.8%) | 1 | 0/34 (0%) | 0 | 0/17 (0%) | 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 | Dr. Rachid Baz |
|---|---|
| Organization | H. Lee Moffitt Cancer Center and Research Institute |
| Phone | 813-745-8212 |
| rachid.baz@moffitt.org |
- MCC-16705
- PO-MM-PI-0039