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

Sponsor:	University of Arkansas
Collaborator:	Celgene Corporation
Information provided by (Responsible Party):	University of Arkansas
ClinicalTrials.gov Identifier:	NCT01177735

Purpose

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	Intervention	Phase
Multiple Myeloma	Drug: Pomalidomide	Phase 2

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia Help Me Understand Genetics

MedlinePlus related topics: Multiple Myeloma

U.S. FDA Resources

Further study details as provided by University of Arkansas:

Primary Outcome Measures:

Progression-free survival (PFS) after initiation of pomalidomide therapy [ Time Frame: 1 year following initiation of pomalidomide therapy ] [ Designated as safety issue: No ]
Progression -free survival (PFS) after initiation of pomalidomide therapy

Secondary Outcome Measures:

Response rate (CR, n-CR, VGPR) and duration of response after pomalidomide therapy. [ Time Frame: 1 year following initiation of pomalidomide therapy ] [ Designated as safety issue: No ]
Response rate (CR, n-CR, VGPR) Duration of response rate after initiation of pomalidomide therapy
Gene expression profiling (GEP) changes exerted within 48 hours of initiation of daily pomalidomide dosing. [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
Gene expression profiling at baseline and at 48 hours after initiation of pomalidomide
Gene expression profiling (GEP) changes exerted within 48 hours of initiation 3 concurrent days of exposure to lenalidomide. [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
Gene expression profiling at 48 hours after initiation of lenalidomide

Estimated Enrollment:	30
Study Start Date:	October 2011
Estimated Study Completion Date:	August 2013
Estimated Primary Completion Date:	August 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: CC-4047

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.

Participants will receive testing dosing of Revlimid 25mg for 2 days followed by GEP sampling. A washout period of at least 24 hours will follow Revlimid prior to starting single agent Pomalidomide at 4 mg/day, days 1-21 every 28 days.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01177735

Contacts

Contact: Nathan Petty	501-526-6990 ext 2435	pettynathanm@uams.edu
Contact: Linda Wood	501-526-6990 ext 2430	woodlindaj@uams.edu

Locations

United States, Arkansas
University of Arkansas for Medical Sciences, Myeloma Institute for Research and Therapy	Recruiting
Little Rock, Arkansas, United States, 72205
Contact: Saad Usmani, MD 501-526-6990 ext 2406 susmani@uams.edu
Contact: Nathan Petty 501-526-6990 ext 2435 pettynathanm@uams.edu
Principal Investigator: Bart Barlogie, MD, PhD
Principal Investigator: Bijay Nair, MD
Sub-Investigator: Elias J. Anaissie, MD
Sub-Investigator: Monica Grazziutti, MD
Sub-Investigator: Frits van Rhee, Md, PhD
Sub-Investigator: Sarah Waheed, MD
Sub-Investigator: Joshua Epstein, DSc
Sub-Investigator: Ricky Edmondson, PhD
Sub-Investigator: Schmuel Yaccoby, PhD
Sub-Investigator: Yiming Zhou, PhD
Sub-Investigator: Alejandro Restrepo, MD
Sub-Investigator: Al-Ola Abdallah, MD
Sub-Investigator: Jameel Muzaffar, MD
Sub-Investigator: Lakshmikanth Katragadda, MD
Sub-Investigator: Nisar Ahmad, MD
Sub-Investigator: Saad Usmani, MD
Sub-Investigator: Sajjad Haider, MD
Sub-Investigator: Senu Apewokin, MD
Sub-Investigator: Shebli Atrash, MD
Sub-Investigator: Stephen Medlin, DO
Sub-Investigator: Zainab Shahid, MD

Sponsors and Collaborators

University of Arkansas

Celgene Corporation

Investigators

Principal Investigator:

Saad Usmani, MD

University of Arkansas for Medical Sciences, Myeloma Institute for Research and Therapy

More Information

Additional Information:

Myeloma Institute for Research and Therapy at The University of Arkansas for Medical Sciences This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University of Arkansas
ClinicalTrials.gov Identifier:	NCT01177735 History of Changes
Obsolete Identifiers:	NCT01426503
Other Study ID Numbers:	UARK 2010-01
Study First Received:	May 14, 2010
Last Updated:	February 16, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Arkansas:

Pomalidomide
multiple myeloma
relapsed

Additional relevant MeSH terms:

Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

Thalidomide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 23, 2012