Continuous Versus Intermittent Dosing Regimens for Pomalidomide in Relapsed/Refractory Multiple Myeloma

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01319422
• Collaborator: Celgene Corporation (Industry)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 41
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

Lenalidomide has clinical activity in myeloma. The closely related compound, Pomalidomide, may have clinical activity in patients who have previously been treated with lenalidomide and who no longer respond to it. The mechanism of anti-tumor effects of these drugs has been attributed to several effects including anti-angiogenesis, immune activation, and anti-proliferative effects. Recent studies have suggested that these agents can mediate surprisingly rapid biologic effects on human monocytes and T cells. Our hypothesis is that the proximate effects of these drugs will be sensitive and quantitative surrogates of subsequent effects including activation of tumor antigen specific T cells as well as innate immune cells. Understanding the correlation between the pharmacodynamics of these effects with downstream activation using quantitative assays will facilitate the rational development of pomalidomide as immune-modulatory drug in diverse settings as well as its optimal development in myeloma therapy.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Pomalidomide	Phase 2

Detailed Description

Multiple Myeloma (MM) is a common hematologic malignancy characterized by clonal expansion of transformed plasma cells (PCs) in the bone marrow1. Over the past decade, the introduction of immunomodulatory agents (such as thalidomide and lenalidomide) and proteasome inhibitors (such as bortezomib) as effective therapies has altered the therapeutic landscape for multiple myeloma (MM). Following the approval and establishment of thalidomide-containing regimens, such as melphalan, prednisone and thalidomide (MPT) and Thal/Dex, as the standard first-line therapy for newly diagnosed MM (NDMM), lenalidomide in combination with dexamethasone (RD) was approved for the treatment of patients with previously treated multiple myeloma 1 (MM1). However, even with these newly approved agents, MM remains an incurable disease and most patients will eventually relapse and progress after multiple lines of different therapeutic regimens including both lenalidomide as well as bortezomib. Thus there remains a continued need to identify newer agents to maintain long term disease control in these patients.

Thalidomide and its immune-modulatory analogue lenalidomide have clinical activity in myeloma. Pomalidomide, a thalidomide analogue, is an immunomodulatory agent that displays similar anti-angiogenic activity, but far greater anti-proliferative and immunomodulatory activity, compared to the parent drug. Pomalidomide and lenalidomide have been shown to possess very similar pharmacological properties in vitro, including anti-angiogenic, immunomodulatory and anti-proliferative properties. However a unifying molecular mechanism for these diverse effects has been elusive. Pomalidomide and lenalidomide have significantly greater capacity for enhanced costimulation, leading to enhanced activation of innate and adaptive immune cells compared to Thalidomide. Recent studies have yielded the surprising finding that these agents can mediate rapid biologic effects on human monocytes and T cells in culture leading to activation of ras homolog gene family, member A (RhoA) GTPases, and enhanced actin polymerization. Changes in actin cytoskeleton may also contribute to the capacity to these drugs to enhance the formation of immune synapses, Pomalidomide has also been shown to stimulate antibody-dependent cytotoxic T-cell activity (ADCC) in preclinical models.

At tolerated doses (MTD = 2 mg per day (QD) and 5 mg every other day (QOD), pomalidomide has been shown to be active in subjects with relapsed or refractory multiple myeloma (study CC-4047-00-001). In 45 subjects who received doses of pomalidomide ranging, by cohort, up to 10 mg daily, the most commonly occurring dose-limiting toxicity (DLT) was reversible neutropenia. As with other immunomodulatory drugs (IMiDs) administered to subjects receiving concomitant systemic steroids, deep vein thrombosis (DVT) was seen (in 1 subject each in this study and in its subsequent named patient supply rollover program).

Recently, preliminary efficacy and safety data from an ongoing phase II study, led by Martha Lacy at Mayo Clinic, were published. Sixty patients with relapsed or refractory multiple myeloma were enrolled. Pomalidomide (CC-4047) was given orally at a dose of 2 mg daily on days 1-28 of a 28-day cycle and dexamethasone was given orally at a dose of 40 mg daily on days 1, 8, 15, 22 of each cycle. Patient also received aspirin 325 mg once daily for thromboprophylaxis. The study endpoints were the response rate in patients taking pomalidomide plus dexamethasone including patients with lenalidomide resistant refractory multiple myeloma, and safety of pomalidomide plus dexamethasone. Responses were recorded using the criteria of the International Myeloma Working Group. Thirty eight patients achieved objective response (63%) including complete response (CR) in 3 patients (5%), very good partial response (VGPR) in 17 patients (28%), and partial response (PR) in 18 patients (30%). The CR + VGPR rate was 33%. Grade 3 or 4 hematologic toxicity occurred in 23 patients (38%) and consisted of anemia in three patients (5%), thrombocytopenia in two patients (3%) and neutropenia in 21 (35%). Among those that developed grade 3/4 neutropenia, all first experienced the neutropenia in cycle 1-3; no new patients experienced grade 3/4 neutropenia in cycle 4 or later. The most common non-hematological grade 3/4 toxicities were fatigue (17%) and pneumonia (8%). Other grade 3/4 non-hematological toxicities that occurred in less than 5% included diarrhea, constipation, hyperglycemia, and neuropathy. One patient (1.6%) had a thromboembolic event of deep vein thrombosis.

Another dosing regimen for Pomalidomide involved 21/28 day dosing, as in the current dosing regimen for Lenalidomide. In this trial the recommended dose for phase II testing was determined to be 4 mg, 21/28 d. Clinical response (greater than or equal to a partial response (PR)) was observed in 7/25 (28%) patients. While both regimens seem to be clinically active, it is unclear at present as to which regimen leads to greater immune activation or clinical activity.

In addition to MM, pre-clinical data and the prior experience with thalidomide and lenalidomide in the treatment of patients with myelofibrosis with myeloid metaplasia (MMM) provided the rationale for the use of pomalidomide in patients with MMM. This is further supported by the results of a Celgene sponsored trial (MMM-001) which indicated that pomalidomide therapy at 0.5 mg or 2 mg/day +/- an abbreviated course of prednisone is well tolerated in patients with myelofibrosis and active in the treatment of anemia.

However, these studies did not monitor proximate pharmacodynamic events (such as might occur within hours of drug exposure), and link these to downstream effects, including clinical activity and toxicity. Our hypothesis is that the proximate effects of these drugs (including drug induced changes in F-actin) and early phosphorylation events will be sensitive and quantitative surrogates of subsequent effects including activation of tumor antigen specific T cells as well as innate immune cells. Understanding the correlation between pharmacodynamics of these effects with downstream activation using quantitative assays will facilitate rational development of these agents as immunomodulatory drugs in diverse settings and may also allow optimization of drug delivery to both reduce potential toxicity, and enhance efficacy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical and Pharmacodynamic Comparison of Continuous Versus Intermittent Dosing Regimens for Pomalidomide in Relapsed/Refractory Multiple Myeloma
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pomalidomide 2 mg/d on 28 days/28 day cycle	Drug: Pomalidomide; Comparison of different dosages and schedules of drug; Other Names: CC-4047
Experimental: Pomalidomide 4 mg/d on 21 days/28 day cycle	Drug: Pomalidomide; Comparison of different dosages and schedules of drug; Other Names: CC-4047

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Response, Analyzed Per International Myeloma Working Group Response Criteria [Efficacy assessments will be made after the first two cycles of therapy (approximately 56 days--each cycle is 28 days)]

   All partial and complete responses must be confirmed with another efficacy assessment in no less than 4 weeks apart.

2. Percentage of Participants With Response, Analyzed Per International Myeloma Working Group Response Criteria [After the initial efficacy assessment at the completion of cycle 2 (at approximately 56 days), efficacy assessments will be made after every other cycle (approximately every 56 days).]

   All partial and complete responses must be confirmed with another efficacy assessment in no less than 4 weeks apart.

Secondary Outcome Measures

1. To Compare the Effect of Continuous Versus Intermittent Regimens on F Actin Polymerization in Peripheral Blood Mononuclear Cells and Activation of Tumor Antigen-specific T Cells, as Well as Innate Lymphocytes (Natural Killer or Natural Killer T Cells). [Research blood draw will be obtained at baseline, and at 2-4 hr (on day 1), 1 wk, and 4 wk after initiation of cycles 1 and 2.]

   Correlation to be determined upon completion of study treatment

2. To Correlate Drug Induced Changes in F Actin Polymerization With Adverse Effects and Clinical Responses. [Research bone marrow aspirate is obtained at baseline and after completion of 2 cycles of therapy (approximately 56 days)]

   Research bone marrow aspirate is obtained to assess response (optional, but recommended), and to document complete remission, if applicable. Correlation to be determined upon completion of study treatment

3. To Correlate Drug Induced Changes in F Actin With Cytokine Profile. [Research blood draw will be obtained at baseline, and at 2-4 hr (on day 1), 1 wk, and 4 wk after initiation of cycles 1 and 2.]

   Correlation to be determined upon completion of study treatment

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Understand and voluntarily sign an informed consent form.

• Age ≥18 years at the time of signing the informed consent form.

• Able to adhere to the study visit schedule and other protocol requirements.

• Relapsed / Refractory Multiple Myeloma following at least two prior standard therapies including lenalidomide. Induction therapy followed by autologous stem cell transplantation (ASCT) is considered one regimen.

• Patients must be refractory to prior lenalidomide therapy. For the purpose of this protocol, refractory will be defined as history of progression on a regimen containing full or maximally tolerated dose of lenalidomide administered for a minimum of at least one complete cycle of therapy.

• All patients must have measurable disease defined as one or more of the following criteria:

• Serum monoclonal protein greater than 10 g/L, serum immunoglobulin free light chain (FLC) more than 10 mg/dL and an abnormal FLC ratio, urine light-chain excretion > 200 mg/24 h, measurable soft tissue plasmacytoma that has not been irradiated, or greater than 30% plasma cells in bone marrow.

• All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 2 weeks prior to treatment in this study.

• Eastern Cooperative Oncology Group (ECOG ) performance status of ≤ 2 at study entry (see Appendix D).

• Laboratory test results within these ranges:

• Absolute neutrophil count ≥ 1.0 x 1000/microliter (uL)

• Platelet count ≥ 75 x 1000/uL

• Serum creatinine ≤ 2.5 mg/dL

• Total bilirubin ≤ 2 mg/dL

• aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 5 x upper limit of normal (ULN)

• Disease free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast.

• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 milli-international unit (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. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Appendix A and B: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, AND also Education and Counseling Guidance Document.

• Able to take aspirin (ASA) (81 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

• Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking pomalidomide).

• Women of child-bearing potential who are unwilling to use a dual method of contraception; and men who are unwilling to use a condom.

• Any condition, including the presence of laboratory abnormalities, which places the subject 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.

• Any prior use of pomalidomide.

• Concurrent use of other anti-cancer agents or treatments.

• Known positive for HIV or active infectious hepatitis, B or C.

• Grade 3 or 4 peripheral neuropathy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University	New Haven	Connecticut	United States	06520

Sponsors and Collaborators

• Yale University
• Celgene Corporation

Investigators

• Principal Investigator: Madhav Dhodapkar, M.D., Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01319422
• Other Study ID Numbers: HIC 1011007607
• First Posted: Mar 21, 2011
• Last Update Posted: Aug 11, 2016
• Last Verified: Jun 1, 2016

• Keywords provided by Yale University: myeloma; multiple myeloma; pomalidomide; immunomodulatory
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Pomalidomide

Study Results

Participant Flow

Recruitment Details	Recruitment took place at an academic medical center.
Pre-assignment Detail	Four screened subjects did not meet eligibility criteria. Forty subjects were enrolled, but one withdrew after randomization without receiving treatment, and is listed as a "non-completer". Thus, data are presented for 39 participants.

Arm/Group Title	Pomalidomide 2 mg/d on 28 Days/28 Day Cycle	Pomalidomide 4 mg/d on 21 Days/28 Day Cycle
Arm/Group Description	Pomalidomide: Comparison of different dosages and schedules of drug	Pomalidomide: Comparison of different dosages and schedules of drug
Period Title: Overall Study
STARTED	20	20
COMPLETED	19	20
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Pomalidomide 2 mg/d on 28 Days/28 Day Cycle	Pomalidomide 4 mg/d on 21 Days/28 Day Cycle	Total
Arm/Group Description	Pomalidomide: Comparison of different dosages and schedules of drug	Pomalidomide: Comparison of different dosages and schedules of drug	Total of all reporting groups
Overall Participants	19	20	39
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63	61	61
Sex: Female, Male (Count of Participants)
Female	9 47.4%	8 40%	17 43.6%
Male	10 52.6%	12 60%	22 56.4%
Immunoglobulin Heavy chain (IgH) type (participants) [Number]
Immunoglobulin G (IgG)	8 42.1%	12 60%	20 51.3%
Immunoglobulin A (IgA)	4 21.1%	1 5%	5 12.8%
Light chain only	7 36.8%	7 35%	14 35.9%
Immunoglobulin Light chain (IgL) type (participants) [Number]
kappa	13 68.4%	15 75%	28 71.8%
lambda	6 31.6%	5 25%	11 28.2%
serum beta 2 microglobulin (mg/L) [Mean (Full Range) ]
Mean (Full Range) [mg/L]	3.0	3.4	3.2
serum albumin (g/dL) [Mean (Full Range) ]
Mean (Full Range) [g/dL]	3.9	3.9	3.9
lines of prior therapy (lines) [Median (Full Range) ]
Median (Full Range) [lines]	4	4	4
Deletion of chromosome 17p (participants) [Number]
yes	4 21.1%	3 15%	7 17.9%
no	10 52.6%	9 45%	19 48.7%
missing	5 26.3%	8 40%	13 33.3%
Chromosome 1q abnormalities (participants) [Number]
yes	10 52.6%	8 40%	18 46.2%
no	9 47.4%	12 60%	21 53.8%
Deletion chromosome 13 (participants) [Number]
yes	5 26.3%	8 40%	13 33.3%
no	14 73.7%	12 60%	26 66.7%
Lenalidomide (Len) as most recent therapy (participants) [Number]
yes	6 31.6%	9 45%	15 38.5%
no	13 68.4%	11 55%	24 61.5%
Resistance to prior therapy-Len refractory (participants) [Number]
yes	19 100%	20 100%	39 100%
no	0 0%	0 0%	0 0%
Resistance to prior therapy-Len+bortezomib refractory (participants) [Number]
yes	15 78.9%	16 80%	31 79.5%
no	4 21.1%	4 20%	8 20.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Response, Analyzed Per International Myeloma Working Group Response Criteria
Description	All partial and complete responses must be confirmed with another efficacy assessment in no less than 4 weeks apart.
Time Frame	Efficacy assessments will be made after the first two cycles of therapy (approximately 56 days--each cycle is 28 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pomalidomide 2 mg/d on 28 Days/28 Day Cycle	Pomalidomide 4 mg/d on 21 Days/28 Day Cycle
Arm/Group Description	Pomalidomide: Comparison of different dosages and schedules of drug	Pomalidomide: Comparison of different dosages and schedules of drug
Measure Participants	19	20
Number [percentage of participants]	15.8 83.2%	20.0 100%

2. Primary Outcome

Title	Percentage of Participants With Response, Analyzed Per International Myeloma Working Group Response Criteria
Description	All partial and complete responses must be confirmed with another efficacy assessment in no less than 4 weeks apart.
Time Frame	After the initial efficacy assessment at the completion of cycle 2 (at approximately 56 days), efficacy assessments will be made after every other cycle (approximately every 56 days).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pomalidomide 2 mg/d on 28 Days/28 Day Cycle	Pomalidomide 4 mg/d on 21 Days/28 Day Cycle
Arm/Group Description	Pomalidomide: Comparison of different dosages and schedules of drug	Pomalidomide: Comparison of different dosages and schedules of drug
Measure Participants	19	20
cycle 4	15.8 83.2%	40.0 200%
cycle 6	21.0 110.5%	40.0 200%
cycle 8	21.0 110.5%	45.0 225%
cycle 10	21.0 110.5%	45.0 225%
cycle 12	21.0 110.5%	45.0 225%
cycle 14	21.0 110.5%	45.0 225%

3. Secondary Outcome

Title	To Compare the Effect of Continuous Versus Intermittent Regimens on F Actin Polymerization in Peripheral Blood Mononuclear Cells and Activation of Tumor Antigen-specific T Cells, as Well as Innate Lymphocytes (Natural Killer or Natural Killer T Cells).
Description	Correlation to be determined upon completion of study treatment
Time Frame	Research blood draw will be obtained at baseline, and at 2-4 hr (on day 1), 1 wk, and 4 wk after initiation of cycles 1 and 2.

Outcome Measure Data

Analysis Population Description

N/A: data were not collected on this outcome; initial F actin polymerization assay was unreliable and not reproducible; hence, this outcome could not be pursued.

Arm/Group Title	Pomalidomide 2 mg/d on 28 Days/28 Day Cycle	Pomalidomide 4 mg/d on 21 Days/28 Day Cycle
Arm/Group Description	Pomalidomide: Comparison of different dosages and schedules of drug	Pomalidomide: Comparison of different dosages and schedules of drug
Measure Participants	0	0

4. Secondary Outcome

Title	To Correlate Drug Induced Changes in F Actin Polymerization With Adverse Effects and Clinical Responses.
Description	Research bone marrow aspirate is obtained to assess response (optional, but recommended), and to document complete remission, if applicable. Correlation to be determined upon completion of study treatment
Time Frame	Research bone marrow aspirate is obtained at baseline and after completion of 2 cycles of therapy (approximately 56 days)

Outcome Measure Data

Analysis Population Description

The actin polymerization assay that was to be used for this outcome was not reproducible and data were not analyzed.

Arm/Group Title	Pomalidomide 2 mg/d on 28 Days/28 Day Cycle	Pomalidomide 4 mg/d on 21 Days/28 Day Cycle
Arm/Group Description	Pomalidomide: Comparison of different dosages and schedules of drug	Pomalidomide: Comparison of different dosages and schedules of drug
Measure Participants	0	0

5. Secondary Outcome

Title	To Correlate Drug Induced Changes in F Actin With Cytokine Profile.
Description	Correlation to be determined upon completion of study treatment
Time Frame	Research blood draw will be obtained at baseline, and at 2-4 hr (on day 1), 1 wk, and 4 wk after initiation of cycles 1 and 2.

Outcome Measure Data

Analysis Population Description

The actin polymerization assay that was to be used for this outcome was not reproducible; hence, the cytokine profile of actin polymerized cells could not be pursued. Data were not analyzed.

Arm/Group Title	Pomalidomide 2 mg/d on 28 Days/28 Day Cycle	Pomalidomide 4 mg/d on 21 Days/28 Day Cycle
Arm/Group Description	Pomalidomide: Comparison of different dosages and schedules of drug	Pomalidomide: Comparison of different dosages and schedules of drug
Measure Participants	0	0

Adverse Events

Arm/Group Title	Pomalidomide 4 mg/d on 21 Days/28 Day Cycle		Pomalidomide 2 mg/d on 28 Days/28 Day Cycle
Arm/Group Description	Pomalidomide: Comparison of different dosages and schedules of drug		Pomalidomide: Comparison of different dosages and schedules of drug
All Cause Mortality
	Pomalidomide 4 mg/d on 21 Days/28 Day Cycle		Pomalidomide 2 mg/d on 28 Days/28 Day Cycle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pomalidomide 4 mg/d on 21 Days/28 Day Cycle		Pomalidomide 2 mg/d on 28 Days/28 Day Cycle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/20 (55%)		7/19 (36.8%)
Blood and lymphatic system disorders
Anemia	0/20 (0%)		1/19 (5.3%)
Thrombocytopenia	0/20 (0%)		2/19 (10.5%)
Leukopenia	0/20 (0%)		1/19 (5.3%)
Cardiac disorders
Syncope	1/20 (5%)		1/19 (5.3%)
Thromboembolic event	1/20 (5%)		0/19 (0%)
Cardiac Disorders, other	1/20 (5%)		0/19 (0%)
Endocrine disorders
Hyperglycemia	1/20 (5%)		0/19 (0%)
General disorders
Fever	2/20 (10%)		2/19 (10.5%)
Infections and infestations
Febrile neutropenia	1/20 (5%)		3/19 (15.8%)
Lung infection	3/20 (15%)		2/19 (10.5%)
Infection (Bacteremia)	1/20 (5%)		0/19 (0%)
Upper respiratory infection	1/20 (5%)		0/19 (0%)
Infection (Other-Influenza)	1/20 (5%)		0/19 (0%)
Skin Infection	1/20 (5%)		0/19 (0%)
Musculoskeletal and connective tissue disorders
Hip Fracture	0/20 (0%)		1/19 (5.3%)
Spinal fracture	0/20 (0%)		1/19 (5.3%)
Back Pain	1/20 (5%)		0/19 (0%)
Renal and urinary disorders
Acute Kidney Injury	1/20 (5%)		1/19 (5.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/20 (15%)		0/19 (0%)
Hypoxia	1/20 (5%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Pomalidomide 4 mg/d on 21 Days/28 Day Cycle		Pomalidomide 2 mg/d on 28 Days/28 Day Cycle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/20 (100%)		19/19 (100%)
Blood and lymphatic system disorders
Anemia	10/20 (50%)		6/19 (31.6%)
Neutropenia	9/20 (45%)		5/19 (26.3%)
Leukopenia	15/20 (75%)		12/19 (63.2%)
Thrombocytopenia	9/20 (45%)		6/19 (31.6%)
Cardiac disorders
Hypertension	1/20 (5%)		1/19 (5.3%)
Presyncope	1/20 (5%)		0/19 (0%)
Endocrine disorders
TSH increased	0/20 (0%)		1/19 (5.3%)
T3 increased	0/20 (0%)		1/19 (5.3%)
Libido decreased	1/20 (5%)		0/19 (0%)
Gastrointestinal disorders
Constipation	4/20 (20%)		2/19 (10.5%)
Diarrhea	4/20 (20%)		5/19 (26.3%)
GERD	1/20 (5%)		0/19 (0%)
General disorders
Fatigue	12/20 (60%)		15/19 (78.9%)
Nausea	5/20 (25%)		4/19 (21.1%)
Vomiting	2/20 (10%)		2/19 (10.5%)
Edema Limbs	3/20 (15%)		2/19 (10.5%)
Fever	2/20 (10%)		2/19 (10.5%)
Anorexia	5/20 (25%)		2/19 (10.5%)
Pruritus	5/20 (25%)		3/19 (15.8%)
Hot flashes	5/20 (25%)		2/19 (10.5%)
Dizziness	4/20 (20%)		2/19 (10.5%)
Edema	3/20 (15%)		0/19 (0%)
Pain in extremity	4/20 (20%)		1/19 (5.3%)
Sore throat	2/20 (10%)		0/19 (0%)
Abdominal Pain	1/20 (5%)		1/19 (5.3%)
Dry mouth	1/20 (5%)		1/19 (5.3%)
Weight loss	1/20 (5%)		1/19 (5.3%)
Insomnia	0/20 (0%)		1/19 (5.3%)
Flu-like symptoms	0/20 (0%)		1/19 (5.3%)
Erectile dysfunction	1/20 (5%)		0/19 (0%)
Flatulence	1/20 (5%)		0/19 (0%)
Nasal congestion	1/20 (5%)		0/19 (0%)
Weight gain	1/20 (5%)		0/19 (0%)
Pain	1/20 (5%)		0/19 (0%)
Hepatobiliary disorders
AST increased	5/20 (25%)		3/19 (15.8%)
ALT increased	6/20 (30%)		2/19 (10.5%)
Infections and infestations
Upper respiratory infection	3/20 (15%)		0/19 (0%)
Soft tissue infection	2/20 (10%)		0/19 (0%)
Lung infection	2/20 (10%)		1/19 (5.3%)
Bronchitis	2/20 (10%)		0/19 (0%)
Sinusitis	2/20 (10%)		0/19 (0%)
Productive cough	1/20 (5%)		0/19 (0%)
Urinary tract infection	0/20 (0%)		1/19 (5.3%)
Periodontal disease	0/20 (0%)		1/19 (5.3%)
Infection (other, oral)	1/20 (5%)		0/19 (0%)
Metabolism and nutrition disorders
Hyponatremia	6/20 (30%)		3/19 (15.8%)
Hypokalemia	2/20 (10%)		2/19 (10.5%)
Hypocalcemia	5/20 (25%)		3/19 (15.8%)
Hyperglycemia	1/20 (5%)		1/19 (5.3%)
Hypomagnesemia	0/20 (0%)		1/19 (5.3%)
Hyperkalemia	1/20 (5%)		0/19 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	5/20 (25%)		4/19 (21.1%)
Generalized muscle weakness	2/20 (10%)		1/19 (5.3%)
Back Pain	1/20 (5%)		1/19 (5.3%)
Back Pain	0/20 (0%)		1/19 (5.3%)
Jaw pain	0/20 (0%)		1/19 (5.3%)
Bone pain	1/20 (5%)		0/19 (0%)
Arthralgia	1/20 (5%)		0/19 (0%)
Nervous system disorders
Dysguesia	1/20 (5%)		3/19 (15.8%)
Blurred vision	0/20 (0%)		2/19 (10.5%)
Tremor	4/20 (20%)		3/19 (15.8%)
Headache	4/20 (20%)		0/19 (0%)
Memory impairment	2/20 (10%)		0/19 (0%)
Neuropathy	3/20 (15%)		1/19 (5.3%)
Confusion	1/20 (5%)		1/19 (5.3%)
Gait disturbance	1/20 (5%)		1/19 (5.3%)
Heightened sense of smell	0/20 (0%)		1/19 (5.3%)
Amnesia	0/20 (0%)		1/19 (5.3%)
Vertigo	0/20 (0%)		1/19 (5.3%)
Muscle weakness, lower limb	1/20 (5%)		0/19 (0%)
Psychiatric disorders
Anxiety	2/20 (10%)		0/19 (0%)
Depression	1/20 (5%)		0/19 (0%)
Renal and urinary disorders
Creatinine increased	3/20 (15%)		1/19 (5.3%)
Bladder pain	0/20 (0%)		1/19 (5.3%)
Respiratory, thoracic and mediastinal disorders
Cough	1/20 (5%)		3/19 (15.8%)
Dyspnea	7/20 (35%)		6/19 (31.6%)
Hoarseness	0/20 (0%)		1/19 (5.3%)
Wheezing	1/20 (5%)		0/19 (0%)
Skin and subcutaneous tissue disorders
Rash	5/20 (25%)		1/19 (5.3%)
Erythema	0/20 (0%)		1/19 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.