Investigation of the Enhancement of Response to Hepatitis B Vaccine by Lenalidomide in Plasma Cell Dyscrasias

• Sponsor: Boston VA Research Institute, Inc. (Other)
• Overall Status: Completed
• CT.gov ID: NCT02041325
• Collaborator: Dana-Farber Cancer Institute (Other)
• Enrollment: 38
• Locations: 2
• Arms: 2
• Duration (Months): 108
• Patients Per Site: 19
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a research study to determine if the study drug lenalidomide will increase the body's immune response, which is the body's response against infections or tumors, to hepatitis B vaccine in patients with plasma cell diseases which include multiple myeloma, monoclonal gammopathy of unknown significance (MGUS) and Waldenström's Macroglobulinemia. It is not a study to see if lenalidomide is an effective treatment for plasma cell disease.

Participants in this study have multiple myeloma or other plasma cell disease and have never been vaccinated with hepatitis B vaccine. One of the effects of the drug lenalidomide is to alter the immune system and thereby increase immune response. It also has some effect against cancer cells; therefore, in theory, it may reduce or prevent the growth of cancer cells.

In this study, one-half of the subjects will be chosen at random to receive the study drug and the other half will take a placebo pill (a sugar pill that looks the same as the real medication). This is a double blind study where neither the subjects nor the investigators know whether the patient receives the study drugs or placebo pills. The effects of the active drug lenalidomide will be compared to the effects of the placebo. The results from this study will be also be compared with a similar but separate study to be done on individuals without known disease.

This study expects to enroll 64 subjects and will be carried out at the Boston VA Healthcare System and the Dana Farber Cancer Institute.

Condition or Disease	Intervention/Treatment	Phase
Plasma Cell Disorder	Drug: Lenalidomide; Drug: Placebo	Phase 2

Detailed Description

The primary object of this study is to evaluate the effect of CC-5013 on the response to hepatitis B vaccine in myeloma. Secondary objectives include the evaluation of immunologic and functional genomic changes following CC-55013.

This study will be a two-center, randomized, double-blinded, placebo-controlled trial. A single dose of Hepatitis B vaccine will be administered to subjects. CC-5013 or placebo will be administered for 7 days prior to and 7 days after the vaccine. Collection of samples for immune analysis will be performed prior to the initiation of CC-5013 administration, at the time of vaccination, and 7, 14, and 28 days after vaccination. Safety assessment will be performed at each visit.

Primary Endpoint

• Titer of antibodies to hepatitis B virus Secondary Endpoints

• Immune analysis

• Hepatitis B related T cell response

• Safety profile

All the patients should not have a prior response against hepatitis B surface antigen. The study will be comprised of 64 multiple myeloma patients who have not taken any therapeutic agents in the 30 days prior to enrollment in the study. Subjects will be randomly assigned to receive or not receive CC-5013, and all will be vaccinated. The study is designed to detect a biological difference of 50% with an alpha of 0.05 and a beta of 0.8.

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Official Title: Investigation of the Enhancement of the Response to Hepatitis B Vaccine by Lenalidomide (RevlimidTM, CC-5013) in Plasma Cell Dyscrasias
• Study Start Date: Apr 1, 2005
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide Subjects will receive oral CC-5013 (lenalidomide) at 25 mg qd for 7 days prior to and 7 days after the vaccine.	Drug: Lenalidomide; Subjects will receive oral CC-5013 (lenalidomide) at 25 mg qd for 7 days prior to and 7 days after the vaccine.; Other Names: CC-5013 Revlimid
Placebo Comparator: Placebo Subjects will receive placebo for 7 days prior to and 7 days after the vaccine.	Drug: Placebo; Subjects will receive placebo for 7 days prior to and 7 days after the vaccine.; Other Names: Sugar pill

Outcome Measures

Primary Outcome Measures

1. Positive for Hepatitis B Surface Antigen [6 weeks]

   The number of participants who test positive for the antibody titer against hepatitis B surface antigen (HbSAg).

Secondary Outcome Measures

1. Safety [6 weeks]

   Number of participants with adverse events as a measure of safety and tolerability

2. Quantity of Subjects With a T-cell Response [6 weeks]

   Participants who displayed a T cell responses against HbSAg following vaccination

3. Phenotypic Changes [6 weeks]

   Phenotypic changes in peripheral blood cells following CC-5013 (lenalidomide) administration especially in regards to CD3, CD4, CD8 T cells, and NK and NKT cells.

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.

• Must have confirmed diagnosis of plasma cell disorder.

• Patients with prior thalidomide or CC-5013 (lenalidomide) use are eligible but these agents must have been discontinued at least 4 weeks prior to treatment in this study.

• All previous cancer therapy, including chemotherapy, and dexamethsone must have been discontinued at least 4 weeks prior to treatment in this study. Patients with recent radiation, hormonal therapy and surgery are eligible.

• Patients must not have received prior Hepatitis B vaccination.

• Patient should be negative for antibody against HbSAg.

• ANC >= 1000, Platelets >= 75,000.

• Women of childbearing potential (WCBP) must have a negative urine pregnancy test at screening (Visit 1). In addition, sexually active WCBP must agree to use two of the following adequate forms of contraception throughout the entire study (tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner). A WCBP must agree to have pregnancy tests 4 weeks after her last dose of lenalidomide. Due to the short duration of drug therapy, abstinence would also be a reasonable option.

Exclusion Criteria:

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

• Pregnant or lactating females.

• 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.

• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.

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

• Known HIV, HBV and HCV positivity.

• Clinically significant autoimmune disease.

• Serious intercurrent illness such as active infection requiring IV antibiotics, significant cardiac or pulmonary disease.

• Psychiatric disorder, alcohol or illicit drug use.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Boston Healthcare System	Boston	Massachusetts	United States	02130
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Boston VA Research Institute, Inc.
• Dana-Farber Cancer Institute

Investigators

• Principal Investigator: Nikhil C Munshi, M.D., VA Boston Healthcare System; Harvard Medical School; Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nikhil Munshi, M.D., Associate Professor of Medicine Harvard Medical School; Physician, Boston VA Research Institute, Inc.
• ClinicalTrials.gov Identifier: NCT02041325
• Other Study ID Numbers: IRB 1831
• First Posted: Jan 22, 2014
• Last Update Posted: May 17, 2016
• Last Verified: Apr 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Hepatitis B; Multiple Myeloma; Neoplasms, Plasma Cell; Paraproteinemias; Lenalidomide

Study Results

Participant Flow

Arm/Group Title	Lenalidomide	Placebo
Arm/Group Description	Subjects will receive oral CC-5013 (lenalidomide) at 25 mg qd for 7 days prior to and 7 days after the vaccine.	Subjects will receive placebo for 7 days prior to and 7 days after the vaccine.
Period Title: Overall Study
STARTED	22	16
COMPLETED	19	13
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	Lenalidomide	Placebo	Total
Arm/Group Description	Subjects will receive oral CC-5013 (lenalidomide) at 25 mg qd for 7 days prior to and 7 days after the vaccine.	Subjects will receive placebo for 7 days prior to and 7 days after the vaccine.	Total of all reporting groups
Overall Participants	22	16	38
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	77	67.5	72.3
Sex: Female, Male (Count of Participants)
Female	5 22.7%	6 37.5%	11 28.9%
Male	17 77.3%	10 62.5%	27 71.1%
Region of Enrollment (Number) [Number]
United States	22 100%	16 100%	38 100%

Outcome Measures

1. Primary Outcome

Title	Positive for Hepatitis B Surface Antigen
Description	The number of participants who test positive for the antibody titer against hepatitis B surface antigen (HbSAg).
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide	Placebo
Arm/Group Description	Subjects will receive oral CC-5013 (lenalidomide) at 25 mg qd or placebo for 2 weeks. Lenalidomide: Subjects will receive oral CC-5013 (lenalidomide) at 25 mg qd or placebo for 2 weeks.	Placebo will be administered for 7 days prior to and 7 days after the vaccine. Placebo: Placebo will be administered for 7 days prior to and 7 days after the vaccine.
Measure Participants	22	16
Number [participants]	4 18.2%	3 18.8%

2. Secondary Outcome

Title	Safety
Description	Number of participants with adverse events as a measure of safety and tolerability
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide	Placebo
Arm/Group Description	Subjects will receive oral CC-5013 (lenalidomide) at 25 mg qd for 7 days prior to and 7 days after the vaccine.	Subjects will receive placebo for 7 days prior to and 7 days after the vaccine.
Measure Participants	22	16
Number [participants]	2 9.1%	2 12.5%

3. Secondary Outcome

Title	Quantity of Subjects With a T-cell Response
Description	Participants who displayed a T cell responses against HbSAg following vaccination
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide	Placebo
Arm/Group Description	Subjects will receive oral CC-5013 (lenalidomide) at 25 mg qd for 7 days prior to and 7 days after the vaccine. Lenalidomide: Subjects will receive oral CC-5013 (lenalidomide) at 25 mg qd for 7 days prior to and 7 days after the vaccine.	Subjects will receive placebo for 7 days prior to and 7 days after the vaccine. Placebo: Subjects will receive placebo for 7 days prior to and 7 days after the vaccine.
Measure Participants	22	16
Number [participants]	0 0%	0 0%

4. Secondary Outcome

Title	Phenotypic Changes
Description	Phenotypic changes in peripheral blood cells following CC-5013 (lenalidomide) administration especially in regards to CD3, CD4, CD8 T cells, and NK and NKT cells.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide	Placebo
Arm/Group Description	Subjects will receive oral CC-5013 (lenalidomide) at 25 mg qd for 7 days prior to and 7 days after the vaccine.	Subjects will receive placebo for 7 days prior to and 7 days after the vaccine.
Measure Participants	22	16
Total T cells CD3+	851.5	715
Helper T cells CD3+/CD4+	591	525
Cytotoxic T cells CD3+/CD8+	296	183
Natural Killer cells CD56+/CD16+	249.5	228

Adverse Events

Arm/Group Title	Lenalidomide		Placebo
Arm/Group Description	Subjects will receive oral CC-5013 (lenalidomide) at 25 mg qd for 7 days prior to and 7 days after the vaccine.		Subjects will receive placebo for 7 days prior to and 7 days after the vaccine.
All Cause Mortality
	Lenalidomide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lenalidomide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/22 (9.1%)		2/16 (12.5%)
Cardiac disorders
Myocardial Infartion	0/22 (0%)	0	1/16 (6.3%)	1
Gastrointestinal disorders
Ischemic Colitis	1/22 (4.5%)	1	0/16 (0%)	0
Injury, poisoning and procedural complications
Bleeding	1/22 (4.5%)	1	0/16 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain	0/22 (0%)	0	1/16 (6.3%)	1
Other (Not Including Serious) Adverse Events
	Lenalidomide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.