Trial Outcomes & Findings for Allogeneic GM-CSF Vaccine and Lenalidomide in Treating Myeloma Patients With Near Complete Remission (NCT NCT01349569)

Last Updated: 2019-01-15

Results Overview

Number of participants who converted from near complete remission (nCR) to complete remission (CR) as measured by the International Myeloma Working Group Uniform Response Criteria. Near complete remission is defined as negative serum and urine electrophoresis, \< 5% plasma cells in the bone marrow, and positive serum and/or urine immunofixation. Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with \< 5% plasma cells.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

Up to 1 year

Results posted on

2019-01-15

Participant Flow

Two participants were screen failures. One participant withdrew consent prior to starting the study.

Participant milestones

Participant milestones
Measure	Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide Lenalidomide: Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle). Allogeneic Myeloma Vaccine: A total of 4 vaccines will be administered. The first three at monthly intervals and a booster at 6 months from the initial vaccine. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed. Prevnar-13: Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.
Overall Study STARTED	16
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide Lenalidomide: Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle). Allogeneic Myeloma Vaccine: A total of 4 vaccines will be administered. The first three at monthly intervals and a booster at 6 months from the initial vaccine. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed. Prevnar-13: Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.
Overall Study Lack of Efficacy	4

Baseline Characteristics

Allogeneic GM-CSF Vaccine and Lenalidomide in Treating Myeloma Patients With Near Complete Remission

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide n=16 Participants Lenalidomide: Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle). Allogeneic Myeloma Vaccine: A total of 4 vaccines will be administered. The first three at monthly intervals and a booster at 6 months from the initial vaccine. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed. Prevnar-13: Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants
Age, Continuous	68 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 1 year

Population: Out of the 16 baseline participants, one received only one dose of vaccine and then had progression of disease. He was replaced and not included in this analysis.

Outcome measures

Outcome measures
Measure	Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide n=15 Participants Lenalidomide: Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle). Allogeneic Myeloma Vaccine: A total of 4 vaccines will be administered. The first three at monthly intervals and a booster at 6 months from the initial vaccine. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed. Prevnar-13: Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.	GVAX Vaccine Allogeneic Myeloma Vaccine: A total of 4 doses will be administered. The first three at monthly intervals and a booster at 6 months from the initial dose. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed.	Prevnar Vaccine Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.
Response Conversion Rate	8 Participants	—	—

SECONDARY outcome

Timeframe: Up to 4 years

Population: Out of the 16 baseline participants, one received only one dose of vaccine and then had progression of disease. He was replaced and not included in this analysis.

Median time for conversion of response from near complete remission (nCR) to complete remission (CR) as measured by the International Myeloma Working Group Uniform Response Criteria. Near complete remission is defined as negative serum and urine electrophoresis, \< 5% plasma cells in the bone marrow, and positive serum and/or urine immunofixation. Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with \< 5% plasma cells. as measured by immunofixation converting from positive to negative.

Outcome measures

Outcome measures
Measure	Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide n=15 Participants Lenalidomide: Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle). Allogeneic Myeloma Vaccine: A total of 4 vaccines will be administered. The first three at monthly intervals and a booster at 6 months from the initial vaccine. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed. Prevnar-13: Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.	GVAX Vaccine Allogeneic Myeloma Vaccine: A total of 4 doses will be administered. The first three at monthly intervals and a booster at 6 months from the initial dose. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed.	Prevnar Vaccine Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.
Time to Response	11.7 months Interval 2.0 to 47.0	—	—

SECONDARY outcome

Timeframe: Baseline, Cycle 3 Day 14, Cycle 6 Day 14, and 1 year

Population: Data was not collected for this outcome measure due to technical difficulties in the assay.

Measures of stem cell population and plasma cell population.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 1 year

Number of participants who experienced grade 3-4 toxicity as per CTCAE 4.0.

Outcome measures

Outcome measures
Measure	Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide n=16 Participants Lenalidomide: Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle). Allogeneic Myeloma Vaccine: A total of 4 vaccines will be administered. The first three at monthly intervals and a booster at 6 months from the initial vaccine. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed. Prevnar-13: Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.	GVAX Vaccine Allogeneic Myeloma Vaccine: A total of 4 doses will be administered. The first three at monthly intervals and a booster at 6 months from the initial dose. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed.	Prevnar Vaccine Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.
Grade 3-4 Toxicity	0 Participants	—	—

SECONDARY outcome

Timeframe: Baseline, Cycle 3 Day 14, end of study (up to 1 year)

Population: Out of the 16 baseline participants, one received only one dose of vaccine and then had progression of disease. He was replaced and not included in this analysis. Only 8/15 participants experienced complete response (CR), therefore only 8 participants analyzed in the CR rows and 7 participants analyzed in the progressive disease (PD) rows.

Immunity is measured by the percentage of CD3+/CSFSE-low/IFN-gamma+ cells. A positive result for a given participant is defined as greater than two standard deviations above that participant's baseline. The data are presented as three groups because the responses were analyzed separately, but all participants were part of the single study arm as represented by the remainder of the record. GVAX-specific immune response and Prevnar-specific immune response was assessed in the same patient by using GVAX and Prevnar-specific co-markers.

Outcome measures

Outcome measures
Measure	Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide n=15 Participants Lenalidomide: Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle). Allogeneic Myeloma Vaccine: A total of 4 vaccines will be administered. The first three at monthly intervals and a booster at 6 months from the initial vaccine. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed. Prevnar-13: Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.	GVAX Vaccine n=15 Participants Allogeneic Myeloma Vaccine: A total of 4 doses will be administered. The first three at monthly intervals and a booster at 6 months from the initial dose. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed.	Prevnar Vaccine n=15 Participants Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.
Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells Complete Response (CR) patients at Baseline	1.2 percentage of cells Standard Deviation 0.4	0.36 percentage of cells Standard Deviation 0.6	0 percentage of cells Standard Deviation NA Mean percentage of CD3+/CSFSE-low/IFN-gamma+ cells was zero, therefore no standard of deviation
Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells CR patients at Cycle 3 Day 14	7.3 percentage of cells Standard Deviation 2.6	13.3 percentage of cells Standard Deviation 3	4.54 percentage of cells Standard Deviation 2.1
Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells CR patients at end of Study	6.3 percentage of cells Standard Deviation 1.4	13.7 percentage of cells Standard Deviation 5.1	3.6 percentage of cells Standard Deviation 1.4
Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells Progressive Disease (PD) patients at Baseline	0.43 percentage of cells Standard Deviation 0.44	0.45 percentage of cells Standard Deviation 0.7	0 percentage of cells Standard Deviation NA Mean percentage of CD3+/CSFSE-low/IFN-gamma+ cells was zero, therefore no standard of deviation
Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells PD patients at Cycle 3 Day 14	1.7 percentage of cells Standard Deviation 2.9	5.7 percentage of cells Standard Deviation 1.4	0 percentage of cells Standard Deviation NA Mean percentage of CD3+/CSFSE-low/IFN-gamma+ cells was zero, therefore no standard of deviation
Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells PD patients at end of study	0.4 percentage of cells Standard Deviation 0	0.21 percentage of cells Standard Deviation 0	1.7 percentage of cells Standard Deviation 0

Adverse Events

Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide n=16 participants at risk Lenalidomide: Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle). Allogeneic Myeloma Vaccine: A total of 4 vaccines will be administered. The first three at monthly intervals and a booster at 6 months from the initial vaccine. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed. Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	6.2% 1/16 • Number of events 1 • Up to 1 year Adverse events were assessed every 28 days.

Other adverse events

Other adverse events
Measure	Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide n=16 participants at risk Lenalidomide: Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle). Allogeneic Myeloma Vaccine: A total of 4 vaccines will be administered. The first three at monthly intervals and a booster at 6 months from the initial vaccine. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed. Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	6.2% 1/16 • Number of events 1 • Up to 1 year Adverse events were assessed every 28 days.
Respiratory, thoracic and mediastinal disorders Chest congestion	6.2% 1/16 • Number of events 1 • Up to 1 year Adverse events were assessed every 28 days.
Cardiac disorders Chest pressure	6.2% 1/16 • Number of events 1 • Up to 1 year Adverse events were assessed every 28 days.
Musculoskeletal and connective tissue disorders Pain - chest wall	6.2% 1/16 • Number of events 1 • Up to 1 year Adverse events were assessed every 28 days.
Cardiac disorders Congestive heart failure	12.5% 2/16 • Number of events 2 • Up to 1 year Adverse events were assessed every 28 days.
Gastrointestinal disorders Constipation	6.2% 1/16 • Number of events 2 • Up to 1 year Adverse events were assessed every 28 days.
Investigations Creatinine increased	12.5% 2/16 • Number of events 2 • Up to 1 year Adverse events were assessed every 28 days.
Gastrointestinal disorders Diarrhea	18.8% 3/16 • Number of events 3 • Up to 1 year Adverse events were assessed every 28 days.
Nervous system disorders Dizziness	6.2% 1/16 • Number of events 1 • Up to 1 year Adverse events were assessed every 28 days.
Cardiac disorders Peripheral edema	12.5% 2/16 • Number of events 2 • Up to 1 year Adverse events were assessed every 28 days.
General disorders Fatigue	18.8% 3/16 • Number of events 3 • Up to 1 year Adverse events were assessed every 28 days.
Skin and subcutaneous tissue disorders Injection site reactions	93.8% 15/16 • Number of events 40 • Up to 1 year Adverse events were assessed every 28 days.
Eye disorders Interface haze	6.2% 1/16 • Number of events 1 • Up to 1 year Adverse events were assessed every 28 days.
Skin and subcutaneous tissue disorders Lump - left wrist	6.2% 1/16 • Number of events 1 • Up to 1 year Adverse events were assessed every 28 days.
Musculoskeletal and connective tissue disorders Cramping	18.8% 3/16 • Number of events 3 • Up to 1 year Adverse events were assessed every 28 days.
Gastrointestinal disorders Nausea	6.2% 1/16 • Number of events 1 • Up to 1 year Adverse events were assessed every 28 days.
Musculoskeletal and connective tissue disorders Pain - knee	6.2% 1/16 • Number of events 1 • Up to 1 year Adverse events were assessed every 28 days.
Gastrointestinal disorders Pain - mouth	6.2% 1/16 • Number of events 1 • Up to 1 year Adverse events were assessed every 28 days.
Musculoskeletal and connective tissue disorders Pain - right side	6.2% 1/16 • Number of events 1 • Up to 1 year Adverse events were assessed every 28 days.
Infections and infestations Pneumonia	6.2% 1/16 • Number of events 1 • Up to 1 year Adverse events were assessed every 28 days.
Skin and subcutaneous tissue disorders Pruritis	12.5% 2/16 • Number of events 3 • Up to 1 year Adverse events were assessed every 28 days.
Gastrointestinal disorders Pain - abdomen	6.2% 1/16 • Number of events 1 • Up to 1 year Adverse events were assessed every 28 days.
Infections and infestations Upper respiratory infection	12.5% 2/16 • Number of events 3 • Up to 1 year Adverse events were assessed every 28 days.

Additional Information

Ivan Borrello, MD

Johns Hopkins University

Phone: 4109554967

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place