Lenalidomide and Vaccine Therapy in Treating Patients With Relapsed or Refractory Multiple Myeloma

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT00445484
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 22
• Location: 1
• Arms: 2
• Duration (Months): 44
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

RATIONALE: Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Vaccines may help the body build an effective immune response to kill cancer cells. Giving lenalidomide together with vaccine therapy may make a stronger immune response and kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving lenalidomide together with vaccine therapy works in treating patients with relapsed or refractory multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: pneumococcal polyvalent vaccine; Drug: lenalidomide	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine whether lenalidomide can augment the efficacy of pneumococcal polyvalent vaccine as it correlates with lenalidomide-induced antitumor efficacy in patients with relapsed or refractory multiple myeloma.

Secondary

• Determine the antibody responses to pneumococcal serotypes in patients treated with this regimen.

• Determine T-cell responses to the carrier protein CRM 197 in patients treated with this regimen.

• Determine the ability of lenalidomide to augment in vivo immune responsiveness as measured by cutaneous delayed-type hypersensitivity (DTH) reactions to Candida and tetanus in these patients.

• Determine the ability of lenalidomide to prime and/or boost systemic vaccine responses in both peripheral blood lymphocytes and marrow lymphocytes in these patients.

OUTLINE: Patients are assigned to 1 of 2 treatment groups.

• Group 1: Patients receive oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive pneumococcal polyvalent vaccine intramuscularly (IM) 14 days prior to beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine).

• Group 2: Patients receive lenalidomide as in group 1. Patients receive pneumococcal polyvalent vaccine IM approximately 45 days after beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine).

After completion of study treatment, patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Revlimid to Augment Efficacy of Prevnar Vaccines in Patients With Relapsed or Refractory Myeloma
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Patients receive oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive pneumococcal polyvalent vaccine intramuscularly (IM) 14 days prior to beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine).	Biological: pneumococcal polyvalent vaccine; Given intramuscularly; Drug: lenalidomide; Given orally
Experimental: Group 2 Patients receive lenalidomide as in group 1. Patients receive pneumococcal polyvalent vaccine IM approximately 45 days after beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine).	Biological: pneumococcal polyvalent vaccine; Given intramuscularly; Drug: lenalidomide; Given orally

Outcome Measures

Primary Outcome Measures

1. 6B Antibody Response to Prevnar Vaccine in Peripheral Blood [basline and 8 weeks after second vaccination]

   Serum IgG levels against the PVC serotype were measured by ELISA

2. 14F Antibody Response to Prevnar Vaccine in Peripheral Blood [basline and 8 weeks after second vaccination]

   Serum IgG levels against the PVC serotype were measured by ELISA

3. 19F Antibody Response to Prevnar Vaccine in Peripheral Blood [basline and 8 weeks after second vaccination]

   Serum IgG levels against the PVC serotype were measured by ELISA

4. 23F Antibody Response to Prevnar Vaccine in Peripheral Blood [basline and 8 weeks after second vaccination]

   Serum IgG levels against the PVC serotype were measured by ELISA

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma (MM) meeting all of the following criteria:

• Relapsed or refractory disease

• Previously received ≥ 2 courses of antimyeloma treatment

• Measurable levels of myeloma paraprotein in serum (> 0.5 g/dL) or urine (> 0.2 g/24-hour urine collection) OR serum-free light-chain disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Absolute neutrophil count ≥ 1,000/mm^3

• Platelet count ≥ 75,000/mm^3

• Creatinine ≤ 2.5 mg/dL

• Bilirubin ≤ 2.0 mg/dL

• AST and ALT ≤ 3 times upper limit of normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use 2 methods of highly effective contraception ≥ 4 weeks before, during, and for 4 weeks after completion of study therapy

• No other malignancy within the past 5 years except treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast

• No serious medical condition, laboratory abnormality, or psychiatric illness that would preclude study treatment or put patient at unacceptable risk

• No known hypersensitivity to thalidomide or lenalidomide

• No development of erythema nodosum in the presence of a reaction characterized by a desquamating rash while taking thalidomide or similar drugs

• No known hypersensitivity to any component of the pneumococcal polyvalent vaccine, including diphtheria toxin or CRM 197

• No known HIV positivity

• No infectious hepatitis type A, B, or C

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No more than 3 prior treatment regimens for MM

• More than 6 months since prior lenalidomide

• More than 28 days since prior experimental drug or therapy

• More than 1 month since prior systemic antimyeloma therapy

• More than 1 month since prior and no concurrent systemic corticosteroids

• No other concurrent anticancer agents or treatments or investigational agents

• No concurrent thalidomide

• No concurrent radiotherapy

• No other concurrent immune therapy or immunomodulatory agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• National Cancer Institute (NCI)

Investigators

• Study Chair: Ivan Borrello, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00445484
• Other Study ID Numbers: J06102 CDR0000532944; P30CA006973; JHOC-J06102; JHOC-NA_00006008; CELGENE-CC-5013
• First Posted: Mar 9, 2007
• Last Update Posted: Aug 24, 2015
• Last Verified: Aug 1, 2015

• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Lenalidomide; Heptavalent Pneumococcal Conjugate Vaccine

Study Results

Participant Flow

Arm/Group Title	Group 2	Group 1
Arm/Group Description	Patients receive lenalidomide as in group 1. Patients receive pneumococcal polyvalent vaccine IM approximately 45 days after beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). pneumococcal polyvalent vaccine: Given intramuscularly lenalidomide: Given orally	Patients receive oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive pneumococcal polyvalent vaccine intramuscularly (IM) 14 days prior to beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). pneumococcal polyvalent vaccine: Given intramuscularly lenalidomide: Given orally
Period Title: Overall Study
STARTED	11	11
COMPLETED	7	10
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Group 1	Group 2	Total
Arm/Group Description	Patients receive oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive pneumococcal polyvalent vaccine intramuscularly (IM) 14 days prior to beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). pneumococcal polyvalent vaccine: Given intramuscularly lenalidomide: Given orally	Patients receive lenalidomide as in group 1. Patients receive pneumococcal polyvalent vaccine IM approximately 45 days after beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). pneumococcal polyvalent vaccine: Given intramuscularly lenalidomide: Given orally	Total of all reporting groups
Overall Participants	11	11	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.3 (9.0)	65.8 (10.3)	66.0 (9.5)
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 45.5%	6 54.5%	11 50%
>=65 years	6 54.5%	5 45.5%	11 50%
Sex: Female, Male (Count of Participants)
Female	7 63.6%	4 36.4%	11 50%
Male	4 36.4%	7 63.6%	11 50%
Region of Enrollment (participants) [Number]
United States	11 100%	11 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	6B Antibody Response to Prevnar Vaccine in Peripheral Blood
Description	Serum IgG levels against the PVC serotype were measured by ELISA
Time Frame	basline and 8 weeks after second vaccination

Outcome Measure Data

Analysis Population Description

Patients who showed evidence of disease progression while on study were not included in the analysis.

Arm/Group Title	Vaccine Started 14 Days Prior to Lenalidomide	Vaccine Started 45 Days After Lenalidomide
Arm/Group Description	Patients receive oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive pneumococcal polyvalent vaccine intramuscularly (IM) 14 days prior to beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). pneumococcal polyvalent vaccine: Given intramuscularly lenalidomide: Given orally	Patients receive lenalidomide as in group 1. Patients receive pneumococcal polyvalent vaccine IM approximately 45 days after beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). pneumococcal polyvalent vaccine: Given intramuscularly lenalidomide: Given orally
Measure Participants	8	5
Mean (Standard Error) [fold change]	3.69 (1.1)	7.58 (3.0)

2. Primary Outcome

Title	14F Antibody Response to Prevnar Vaccine in Peripheral Blood
Description	Serum IgG levels against the PVC serotype were measured by ELISA
Time Frame	basline and 8 weeks after second vaccination

Outcome Measure Data

Analysis Population Description

Patients who showed evidence of disease progression while on study were not included in the analysis.

Arm/Group Title	Vaccine Started 14 Days Prior to Lenalidomide	Vaccine Started 45 Days After Lenalidomide
Arm/Group Description	Patients receive oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive pneumococcal polyvalent vaccine intramuscularly (IM) 14 days prior to beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). pneumococcal polyvalent vaccine: Given intramuscularly lenalidomide: Given orally	Patients receive lenalidomide as in group 1. Patients receive pneumococcal polyvalent vaccine IM approximately 45 days after beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). pneumococcal polyvalent vaccine: Given intramuscularly lenalidomide: Given orally
Measure Participants	5	8
Mean (Standard Error) [fold change]	9.42 (5.0)	11.95 (3.8)

3. Primary Outcome

Title	19F Antibody Response to Prevnar Vaccine in Peripheral Blood
Description	Serum IgG levels against the PVC serotype were measured by ELISA
Time Frame	basline and 8 weeks after second vaccination

Outcome Measure Data

Analysis Population Description

Patients who showed evidence of disease progression while on study were not included in the analysis.

Arm/Group Title	Vaccine Started 14 Days Prior to Lenalidomide	Vaccine Started 45 Days After Lenalidomide
Arm/Group Description	Patients receive oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive pneumococcal polyvalent vaccine intramuscularly (IM) 14 days prior to beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). pneumococcal polyvalent vaccine: Given intramuscularly lenalidomide: Given orally	Patients receive lenalidomide as in group 1. Patients receive pneumococcal polyvalent vaccine IM approximately 45 days after beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). pneumococcal polyvalent vaccine: Given intramuscularly lenalidomide: Given orally
Measure Participants	8	5
Mean (Standard Error) [fold change]	2.025 (0.64)	2.12 (0.4)

4. Primary Outcome

Title	23F Antibody Response to Prevnar Vaccine in Peripheral Blood
Description	Serum IgG levels against the PVC serotype were measured by ELISA
Time Frame	basline and 8 weeks after second vaccination

Outcome Measure Data

Analysis Population Description

Patients who showed evidence of disease progression while on study were not included in the analysis.

Arm/Group Title	Vaccine Started 14 Days Prior to Lenalidomide	Vaccine Started 45 Days After Lenalidomide
Arm/Group Description	Patients receive oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive pneumococcal polyvalent vaccine intramuscularly (IM) 14 days prior to beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). pneumococcal polyvalent vaccine: Given intramuscularly lenalidomide: Given orally	Patients receive lenalidomide as in group 1. Patients receive pneumococcal polyvalent vaccine IM approximately 45 days after beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). pneumococcal polyvalent vaccine: Given intramuscularly lenalidomide: Given orally
Measure Participants	8	5
Mean (Standard Error) [fold change]	4.1 (1.8)	2.42 (1)

Adverse Events

Arm/Group Title	Group 1		Group 2
Arm/Group Description	Patients receive oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive pneumococcal polyvalent vaccine intramuscularly (IM) 14 days prior to beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). pneumococcal polyvalent vaccine: Given intramuscularly lenalidomide: Given orally		Patients receive lenalidomide as in group 1. Patients receive pneumococcal polyvalent vaccine IM approximately 45 days after beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). pneumococcal polyvalent vaccine: Given intramuscularly lenalidomide: Given orally
All Cause Mortality
	Group 1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Group 1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/11 (9.1%)		0/11 (0%)
Blood and lymphatic system disorders
Thrombocytopenia	1/11 (9.1%)	1	0/11 (0%)	0
Other (Not Including Serious) Adverse Events
	Group 1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/11 (9.1%)		1/11 (9.1%)
Blood and lymphatic system disorders
Anemia	1/11 (9.1%)	1	0/11 (0%)	0
Cardiac disorders
Hypertension	0/11 (0%)	0	1/11 (9.1%)	1
Metabolism and nutrition disorders
Hyperlipidemia	0/11 (0%)	0	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Lower back pain	1/11 (9.1%)	1	0/11 (0%)	0
Renal and urinary disorders
Renal insufficiency	0/11 (0%)	0	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Shortness of breath on exertion	1/11 (9.1%)	1	0/11 (0%)	0
Cough	0/11 (0%)	0	1/11 (9.1%)	1
Skin and subcutaneous tissue disorders
Rash	0/11 (0%)	0	1/11 (9.1%)	1

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.