Trial Outcomes & Findings for Universal Granulocyte Macrophage-colony Stimulating Factor (GM-CSF)-Producing and GM.CD40L for Autologous Tumor Vaccine in Mantle Cell Lymphoma (NCT NCT00101101)

Last Updated: 2023-08-22

Results Overview

Immunological response to vaccination, as measured by in vitro testing of peripheral blood mononuclear cells (PBMCs) for interferon gamma secretion, delayed type hypersensitivity reaction (DTH) in response to irradiated autologous tumor cells, and lymphocyte accumulation at DTH and vaccine injection sites. DTH Skin Testing was performed within 2 weeks prior to first vaccine, and again after fourth vaccine was administered. Aliquots containing 10\^6 irradiated autologous tumor cells were re-suspended in 0.2 mL of Plasma-Lyte A and injected intradermally in the forearm and marked. 48 hours later, injection site was inspected for induration and erythema. 3mm punch biopsy of DTH injection site and vaccine site was obtained 48 hours after administration of irradiated tumor cells before and after the vaccine series. Vaccine site biopsy was obtained 2-5 days after the second vaccine had been given. Granulocytic and lymphocytic accumulation at these sites was graded by a pathologist.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

43 participants

Primary outcome timeframe

4 months per participant

Results posted on

2023-08-22

Participant Flow

Forty three patients with stage II-IV histologically confirmed mantle cell lymphoma (MCL) in need of systemic chemotherapy were enrolled at the H. Lee Moffitt Cancer Center between February 2004 and July 2008.

Participant milestones

Participant milestones
Measure	Vaccine and Conventional Therapy Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	43
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Vaccine and Conventional Therapy Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity.
Overall Study never received vaccine	20

Baseline Characteristics

Universal Granulocyte Macrophage-colony Stimulating Factor (GM-CSF)-Producing and GM.CD40L for Autologous Tumor Vaccine in Mantle Cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vaccine and Conventional Therapy n=43 Participants Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants
Age, Categorical >=65 years	25 Participants n=5 Participants
Age, Continuous	65 participants n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants
Region of Enrollment United States	43 participants n=5 Participants

PRIMARY outcome

Timeframe: 4 months per participant

Population: Participants who received at least one vaccine injection.

Outcome measures

Outcome measures
Measure	Vaccine and Conventional Therapy n=23 Participants Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity.
Rate of Immunological Response to Vaccination Clinical DTH	0 participants
Rate of Immunological Response to Vaccination Increase in Interferon Gamma Secretion	15 participants

SECONDARY outcome

Timeframe: 4 months per participant

Population: Participants who received at least one vaccine injection.

Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase. This included clinical and laboratory evaluation (CBC, blood urea nitrogen (BUN), creatinine, electrolytes, liver function test (LFT), and serum LDH). Toxicity was defined according to the NCI Common Terminology Criteria for Adverse Events (CTCAE-3) Version 3.0 (www.ctep.cancer.gov). Grade 3 or higher SAEs attributed to vaccination: Toxicity was assessed in the 23 patients who received at least one vaccine injection.

Outcome measures

Outcome measures
Measure	Vaccine and Conventional Therapy n=23 Participants Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity.
Occurrence of Related Serious Adverse Events (SAEs)	0 participants

SECONDARY outcome

Timeframe: 18 months

Population: Participants who received at least one vaccine injection.

Vaccine Response - EFS among participants who received vaccination. Event free survival (EFS) was calculated from date of enrollment until progression or death from any cause. Progressive disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Vaccine and Conventional Therapy n=23 Participants Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity.
Median Event Free Survival (EFS)	9 months Interval 5.0 to 18.0

Adverse Events

Vaccine and Conventional Therapy

Serious events: 2 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Vaccine and Conventional Therapy n=43 participants at risk Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Leukocyte	2.3% 1/43 • Number of events 2 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
Blood and lymphatic system disorders Granulocyte	2.3% 1/43 • Number of events 2 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
Respiratory, thoracic and mediastinal disorders Cough	2.3% 1/43 • Number of events 1 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.

Other adverse events

Other adverse events
Measure	Vaccine and Conventional Therapy n=43 participants at risk Patients were treated with 3-6 cycles of chemotherapy +/- rituximab, with type and duration at the discretion of the individual clinician. Chemotherapy: 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) OR 3 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) for patients who have relapsed after CHOP. Patients who achieve a partial or complete response after completion of chemotherapy proceed to autologous tumor cell-based vaccine therapy. Patients who have stable or responding disease at 12 months receive 4 additional courses of booster vaccine and low-dose IL-2. Treatment continues in the absence of disease progression or unacceptable toxicity.
Skin and subcutaneous tissue disorders Injection site reaction/extravasation changes	25.6% 11/43 • Number of events 25 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
General disorders Fatigue (asthenia, lethargy, malaise)	18.6% 8/43 • Number of events 10 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
General disorders Fever (in the absence of neutropenia)	4.7% 2/43 • Number of events 2 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
Blood and lymphatic system disorders Hemoglobin	14.0% 6/43 • Number of events 6 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
Blood and lymphatic system disorders Platelets	7.0% 3/43 • Number of events 3 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
Blood and lymphatic system disorders Neutrophils/granulocytes	4.7% 2/43 • Number of events 2 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
Blood and lymphatic system disorders Leukocytes (total WBC)	4.7% 2/43 • Number of events 2 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
General disorders Pain - Joint	9.3% 4/43 • Number of events 4 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
General disorders Pain - Head/headache	4.7% 2/43 • Number of events 3 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
Gastrointestinal disorders Diarrhea	4.7% 2/43 • Number of events 2 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
Gastrointestinal disorders Nausea	4.7% 2/43 • Number of events 2 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
Gastrointestinal disorders Vomiting	4.7% 2/43 • Number of events 2 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
Respiratory, thoracic and mediastinal disorders Cough	7.0% 3/43 • Number of events 4 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	4.7% 2/43 • Number of events 2 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
Metabolism and nutrition disorders Alkaline phosphatase	4.7% 2/43 • Number of events 2 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
Metabolism and nutrition disorders Calcium, serum-high (hypercalcemia)	4.7% 2/43 • Number of events 4 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	4.7% 2/43 • Number of events 2 • Patients were monitored for toxicity every 4 weeks in clinic throughout the 4-month vaccination phase.

Additional Information

Sophie Dessureault, M.D., Ph.D.

H. Lee Moffitt Cancer Center and Research Institute

Phone: 813-745-1965

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place