Pomalidomide in Gene Expression Profiling (GEP)-Defined High-risk Multiple Myeloma

• Sponsor: University of Arkansas (Other)
• Overall Status: Completed
• CT.gov ID: NCT01177735
• Collaborator: Celgene (Industry)
• Enrollment: 71
• Location: 1
• Arm: 1
• Duration (Months): 23
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

This is a phase II study, open-label, single institution trial of pomalidomide in GEP-defined, high-risk relapsing/refractory multiple myeloma. Prior therapy must have included lenalidomide. Patient accrual is 30 over a 2 year period.

Primary objective:

• To determine progression-free survival (PFS) after initiation of pomalidomide therapy

Secondary objective:

• To determine the response rate (CR, n-CR, VGPR) and duration of response after pomalidomide therapy.

• To determine gene expression profiling (GEP) changes exerted within 48 hours of initiation of daily pomalidomide dosing.

• To determine gene expression profiling (GEP) changes exerted within 48 hours of initiation 3 concurrent days of exposure to lenalidomide.

• To determine MRI- and PET-CT-defined CR in studies obtained at baseline and every 6 month examinations.

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

Detailed Description

Pomalidomide is a 2nd generation immunomodulatory agent (IMiD®) with greater efficacy than lenalidomide and with a similar toxicity spectrum. Phase I trials have shown that pomalidomide 1 to 5 mg is well-tolerated1,2.

TT3 has been remarkably successful in the management of newly diagnosed MM, inducing CR rates of >60% and 4-year estimates of overall and event-free survival of 85% and 75%. Of those achieving CR, estimated 4-year CR rate is 85%. TT3 maintenance has been with either VTD in 2003-33 or VRD in 2006-66, so that pomalidomide's role in overcoming refractoriness to lenalidomide can be assessed.

Pharmacogenomic investigations comparing GEP data obtained at baseline and 48hr post-treatment have been performed in case of thalidomide, dexamethasone, lenalidomide, bortezomib and melphalan3. Thus, as most patients on TT3 had baseline and 48-hr GEP investigations performed after bortezomib, the opportunity exists to investigate, at the time of relapse, not only a re-challenge with bortezomib with 48hr GEP but also pomalidomide's effect.

This is a phase II study, open-label, single institution trial of pomalidomide in GEP-defined, high-risk relapsing/refractory multiple myeloma. Prior therapy must have included lenalidomide.

Study Design

• Study Type: Interventional
• Actual Enrollment: 71 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Pomalidomide in GEP-defined High-risk Multiple Myeloma That is Relapsing or Refractory to Prior Therapy
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pomalidomide	Drug: Pomalidomide; Only enough CC-4047 for 1 cycle of therapy may be provided to the patient each cycle. Participants will receive CC-4047 4 mg/day for 21 days, every 28 days. Treatment will continue until disease recurrence or untoward toxicity.; Other Names: CC-4047

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) After Initiation of Pomalidomide Therapy [1 year following initiation of pomalidomide therapy]

   Progression -free survival (PFS) after initiation of pomalidomide therapy. Progressive disease is defined as increase of > 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be > 0.5 g/dL); Urine M-component and/or (the absolute increase must be > 200 mg/24 h); Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be > 10 mg/dL; Bone marrow plasma cell percentage; the absolute percentage must be > 10%; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participant has multiple myeloma, relapsed or resistant to prior therapy.

• Participant has high-risk disease, as defined by any of the following:

• GEP risk score of > 0.66 OR

• Metaphase based abnormalities of 1q or 1p OR

• LDH > 360 U/L

• Participant has received prior therapy with lenalidomide-containing regimen and has been determined to be refractory, resistant, or relapsed.

• Participant has no significant peripheral neuropathy (< grade 3 by the most current NCI CTCAE version)

• Participant has adequate hematopoietic reserve as defined by platelet count ≥ 50,000/µL and ANC of > 1000/µL.

• Participant has adequate renal function as defined by serum creatinine < 2 mg/dL.

• Participant has adequate hepatic function, defined by serum Total bilirubin </= 1.5 mg/dL and AST (SGOT) and ALT (SGPT) </= x ULN.

• Participant is 18 years of age or greater.

• Participant has not received anti-cancer therapy within 4 weeks prior to treatment on this study.

• Zubrod ≤ 2, unless solely due to symptoms of MM-related bone disease.

• Disease free of prior malignancies for >/= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ 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 mIU/mL within 10 - 14 days prior to and again within 24 hours prior to starting lenalidomide or CC-4047 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 lenalidomide or CC-4047.

• All patients must be informed of the investigational nature of this study and must sign and give written voluntary consent in accordance with institutional and federal guidelines.

• Willing and able to take aspirin or alternate prophylactic anticoagulation.

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.

• Men unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment.

• 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 lenalidomide.

• The development of erythema nodosum if characterized by a desquamating rash while taking lenalidomide, CC-4047 or similar drugs.

• Any prior use of CC-4047.

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

• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.

• Active malignancy (exception of non melanoma skin cancer or in situ cervical or breast cancer).

• Active DVT or PE that has not been therapeutically anticoagulated.

• ≥ grade 3 peripheral neuropathy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences, Myeloma Institute for Research and Therapy	Little Rock	Arkansas	United States	72205

Sponsors and Collaborators

• University of Arkansas
• Celgene

Investigators

• Principal Investigator: Saad Usmani, MD, University of Arkansas for Medical Sciences, Myeloma Institute for Research and Therapy

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Myeloma Institute for Research and Therapy at The University of Arkansas for Medical Sciences

Publications

None provided.

• Responsible Party: University of Arkansas
• ClinicalTrials.gov Identifier: NCT01177735
• Other Study ID Numbers: 113385; UARK 2010-01; NCT01426503
• First Posted: Aug 9, 2010
• Last Update Posted: Apr 22, 2021
• Last Verified: Oct 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Arkansas: Pomalidomide; multiple myeloma; relapsed
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Pomalidomide

Study Results

Participant Flow

Arm/Group Title	Pomalidomide
Arm/Group Description	Pomalidomide: Only enough CC-4047 for 1 cycle of therapy may be provided to the patient each cycle. Participants will receive CC-4047 4 mg/day for 21 days, every 28 days. Treatment will continue until disease recurrence or untoward toxicity.
Period Title: Overall Study
STARTED	71
COMPLETED	0
NOT COMPLETED	71

Baseline Characteristics

Arm/Group Title	Pomalidomide
Arm/Group Description	Pomalidomide: Only enough CC-4047 for 1 cycle of therapy may be provided to the patient each cycle. Participants will receive CC-4047 4 mg/day for 21 days, every 28 days. Treatment will continue until disease recurrence or untoward toxicity.
Overall Participants	71
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.25 (76.161)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	30 42.3%
>=65 years	41 57.7%
Sex: Female, Male (Count of Participants)
Female	28 39.4%
Male	43 60.6%
Region of Enrollment (participants) [Number]
United States	71 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) After Initiation of Pomalidomide Therapy
Description	Progression -free survival (PFS) after initiation of pomalidomide therapy. Progressive disease is defined as increase of > 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be > 0.5 g/dL); Urine M-component and/or (the absolute increase must be > 200 mg/24 h); Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be > 10 mg/dL; Bone marrow plasma cell percentage; the absolute percentage must be > 10%; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
Time Frame	1 year following initiation of pomalidomide therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pomalidomide
Arm/Group Description	Pomalidomide: Only enough CC-4047 for 1 cycle of therapy may be provided to the patient each cycle. Participants will receive CC-4047 4 mg/day for 21 days, every 28 days. Treatment will continue until disease recurrence or untoward toxicity.
Measure Participants	71
Number [percentage of participants]	13 18.3%

Adverse Events

Arm/Group Title	Pomalidomide
Arm/Group Description	Pomalidomide: Only enough CC-4047 for 1 cycle of therapy may be provided to the patient each cycle. Participants will receive CC-4047 4 mg/day for 21 days, every 28 days. Treatment will continue until disease recurrence or untoward toxicity.
All Cause Mortality
	Pomalidomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pomalidomide
	Affected / at Risk (%)	# Events
Total	6/71 (8.5%)
Blood and lymphatic system disorders
Pancytopenia	1/71 (1.4%)	1
Epistaxis	1/71 (1.4%)	1
Blood transfusion	1/71 (1.4%)	1
Cardiac disorders
Atrial Fibrilation	2/71 (2.8%)	2
Hospitalization dyspnea due to congestive heart failure	1/71 (1.4%)	1
Dyspnea on exertion	1/71 (1.4%)	1
Hospitalization for hypotension	2/71 (2.8%)	2
Deep vein thrombosis and cerebrovascular accident	1/71 (1.4%)	1
Hospitalization with fever and low blood pressure	1/71 (1.4%)	1
Tachycardia	1/71 (1.4%)	1
Gastrointestinal disorders
Small bowel obstruction	1/71 (1.4%)	1
Acute diarrhea	1/71 (1.4%)	1
Hospitalization for Pneumonia and gastrointestinal bleeding	1/71 (1.4%)	1
Hospitalization for diarrhea and dizziness	1/71 (1.4%)	1
General disorders
Hypoxia	1/71 (1.4%)	1
Infections and infestations
Hospitalization for sinus infection	1/71 (1.4%)	1
Hospialization for progressive disease, sepsis and pneumonia	3/71 (4.2%)	3
Hospitalization for fever	1/71 (1.4%)	1
RSV Pneumonia	2/71 (2.8%)	2
Fever neutropenia dehydration	1/71 (1.4%)	1
Hospitalization for neutropenic fever	4/71 (5.6%)	4
Hospitalization due to acute liver failure hepatitis B flare	1/71 (1.4%)	1
Hospitalization for pneumonia	1/71 (1.4%)	1
Pneumonia	4/71 (5.6%)	4
Elevated liver function test	1/71 (1.4%)	1
Hospitalization for sepsis	1/71 (1.4%)	1
Pneumonia, fever and altered mental status	1/71 (1.4%)	1
Hospitalization for parainfluenza type 2	1/71 (1.4%)	1
Recurrent multifocal pneumonia	1/71 (1.4%)	1
Acute onset diarrhea and acute renal insufficiency	1/71 (1.4%)	1
Recurrent bilateral pneumonia	1/71 (1.4%)	1
Injury, poisoning and procedural complications
Hospitalization for removal of port	1/71 (1.4%)	1
Fracture of T7 with possible cord compression	1/71 (1.4%)	1
Nervous system disorders
Hospitalization for intractable pain, low fever	1/71 (1.4%)	1
Hospitalization for acute respiratory distress syndrome, encephalopathy, fatigue	1/71 (1.4%)	1
Paraparesis, spinal cord compression	1/71 (1.4%)	1
Psychiatric disorders
Mental status changes and bacteremia	1/71 (1.4%)	1
Renal and urinary disorders
Acute renal failure	2/71 (2.8%)	2
Worsening renal failure	1/71 (1.4%)	1
Respiratory, thoracic and mediastinal disorders
Hospitalization for shortness of breath	1/71 (1.4%)	1
Dyspnea	1/71 (1.4%)	1
Hospitalization for bronchitis	1/71 (1.4%)	1
Respiratory failure secondary to opioid overdose	1/71 (1.4%)	1
Severe cough, shortness of breath and hypoxemia	1/71 (1.4%)	1
Shortness of breath fever chills	1/71 (1.4%)	1
Upper respiratory infection and fever	1/71 (1.4%)	1
Shortness of breath with wheezing	1/71 (1.4%)	1
Surgical and medical procedures
Intrahepatic chemotherapy	1/71 (1.4%)	1
Wrong dosage dispensed	1/71 (1.4%)	1
Vascular disorders
Deep vein thrombosis diagnosis	1/71 (1.4%)	1
Hospitalization due to transient ischemic attack	1/71 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Pomalidomide
	Affected / at Risk (%)	# Events
Total	71/71 (100%)
Blood and lymphatic system disorders
Leukopenia	71/71 (100%)
Thrombocytopenia	71/71 (100%)
Anemia	71/71 (100%)
Lymphatics	10/71 (14.1%)
Cardiac disorders
Cardiac Arrhythmia	7/71 (9.9%)
Cardiac General	12/71 (16.9%)
Eye disorders
Ocular / Vision	6/71 (8.5%)
Gastrointestinal disorders
Gastrointestinal	44/71 (62%)
General disorders
Blood/Bone Marrow	71/71 (100%)
Constitutional Symptoms	55/71 (77.5%)
Pain	40/71 (56.3%)
Hepatobiliary disorders
Hepatobiliary / Pancreas	70/71 (98.6%)
Infections and infestations
Infection	29/71 (40.8%)
Injury, poisoning and procedural complications
Hemorrhage / Bleeding	8/71 (11.3%)
Metabolism and nutrition disorders
Metabolic/Laboratory	66/71 (93%)
Musculoskeletal and connective tissue disorders
Musculoskeletal / Soft Tissue	24/71 (33.8%)
Nervous system disorders
Neurology	55/71 (77.5%)
Renal and urinary disorders
Renal / Genitourinary	45/71 (63.4%)
Respiratory, thoracic and mediastinal disorders
Pulmonary / Upper Respiratory	40/71 (56.3%)
Skin and subcutaneous tissue disorders
Dermatology / Skin	31/71 (43.7%)

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.