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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Lymphoma Research Foundation
Novartis
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00101101
First received: January 7, 2005
Last updated: September 9, 2014
Last verified: September 2014
Results First Received: June 20, 2013  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Lymphoma
Interventions: Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisone
Drug: Dexamethasone
Biological: Autologous Tumor Cell-Based Vaccine
Drug: IL-2

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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.


Participant Flow:   Overall Study
    Vaccine and Conventional Therapy  
STARTED     43  
COMPLETED     23 [1]
NOT COMPLETED     20  
never received vaccine                 20  
[1] Participants who received at least one vaccine injection.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who started the study.

Reporting Groups
  Description
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.


Baseline Measures
    Vaccine and Conventional Therapy  
Number of Participants  
[units: participants]
  43  
Age  
[units: participants]
 
<=18 years     0  
Between 18 and 65 years     18  
>=65 years     25  
Age  
[units: participants]
Median ( Full Range )
  65  
  ( 47 to 81 )  
Gender  
[units: participants]
 
Female     9  
Male     34  
Region of Enrollment  
[units: participants]
 
United States     43  



  Outcome Measures
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1.  Primary:   Rate of Immunological Response to Vaccination   [ Time Frame: 4 months per participant ]

Measure Type Primary
Measure Title Rate of Immunological Response to Vaccination
Measure Description

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.

Time Frame 4 months per participant  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who received at least one vaccine injection.

Reporting Groups
  Description
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.


Measured Values
    Vaccine and Conventional Therapy  
Number of Participants Analyzed  
[units: participants]
  23  
Rate of Immunological Response to Vaccination  
[units: participants]
 
Clinical DTH     0  
Increase in Interferon Gamma Secretion     15  

No statistical analysis provided for Rate of Immunological Response to Vaccination



2.  Secondary:   Occurrence of Related Serious Adverse Events (SAEs)   [ Time Frame: 4 months per participant ]

Measure Type Secondary
Measure Title Occurrence of Related Serious Adverse Events (SAEs)
Measure Description 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.
Time Frame 4 months per participant  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who received at least one vaccine injection.

Reporting Groups
  Description
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.


Measured Values
    Vaccine and Conventional Therapy  
Number of Participants Analyzed  
[units: participants]
  23  
Occurrence of Related Serious Adverse Events (SAEs)  
[units: participants]
  0  

No statistical analysis provided for Occurrence of Related Serious Adverse Events (SAEs)



3.  Secondary:   Median Event Free Survival (EFS)   [ Time Frame: 18 months ]

Measure Type Secondary
Measure Title Median Event Free Survival (EFS)
Measure Description 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.
Time Frame 18 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who received at least one vaccine injection.

Reporting Groups
  Description
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.


Measured Values
    Vaccine and Conventional Therapy  
Number of Participants Analyzed  
[units: participants]
  23  
Median Event Free Survival (EFS)  
[units: months]
Median ( 95% Confidence Interval )
  9  
  ( 5 to 18 )  

No statistical analysis provided for Median Event Free Survival (EFS)




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
With a median follow-up of 67 months, the median overall survival (OS) has not yet been reached.


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Sophie Dessureault, M.D., Ph.D.
Organization: H. Lee Moffitt Cancer Center and Research Institute
phone: 813-745-1965
e-mail: sophie.dessureault@moffitt.org


No publications provided


Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00101101     History of Changes
Other Study ID Numbers: MCC-13840, 0406-654
Study First Received: January 7, 2005
Results First Received: June 20, 2013
Last Updated: September 9, 2014
Health Authority: United States: Food and Drug Administration