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Phase 1-2 of a CpG-Activated Whole Cell Vaccine Followed by Autologous Immunotransplant for MCL

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ClinicalTrials.gov Identifier: NCT00490529
Recruitment Status : Completed
First Posted : June 22, 2007
Results First Posted : January 13, 2020
Last Update Posted : January 13, 2020
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Ronald Levy, Stanford University

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lymphoma, Mantle-Cell
Interventions Biological: CpG-MCL vaccine
Biological: PF-3512676
Procedure: Vaccine-primed T-cells
Procedure: Autologous hematopoietic stem cell transplant (HSCT)
Drug: Rituximab
Drug: Standard induction chemotherapy
Drug: Cyclophosphamide
Drug: Filgrastim
Enrollment 59
Recruitment Details Some participants started study procedures, but did not receive the intended study treatment.
Pre-assignment Details  
Arm/Group Title CpG-MCL Vaccine
Hide Arm/Group Description An autologous anti-tumor vaccine.
Period Title: Completed Pre-CpG-MCL Vaccine Procedures
Started 59
Completed 48
Not Completed 11
Reason Not Completed
Death             4
Withdrawal by Subject             4
Withdrawn, AHCT not suitable treatment             1
Withdrawn, chemo not suitable treatment             1
Withdrawal due to insurance refusal             1
Period Title: Treatment With CpG-MCL Vaccine
Started 48
Completed 47
Not Completed 1
Reason Not Completed
Received vaccine, did not receive AHCT             1
Arm/Group Title CpG-MCL Vaccine
Hide Arm/Group Description An autologous anti-tumor vaccine.
Overall Number of Baseline Participants 59
Hide Baseline Analysis Population Description
Includes all participants that started study procedures. Prospective participants that consented but did not receive any research procedures are not included.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants
<=18 years
0
   0.0%
Between 18 and 65 years
17
  28.8%
>=65 years
42
  71.2%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 59 participants
58  (8.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants
Female
20
  33.9%
Male
39
  66.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants
Hispanic or Latino
3
   5.1%
Not Hispanic or Latino
56
  94.9%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants
American Indian or Alaska Native
0
   0.0%
Asian
3
   5.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   1.7%
White
54
  91.5%
More than one race
0
   0.0%
Unknown or Not Reported
1
   1.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 59 participants
59
1.Primary Outcome
Title Freedom From Molecular Residual Disease (MRD) Post-autologous Stem Cell Transplant (ASCT)
Hide Description Molecular residual disease (MRD) is defined as detection in blood samples by the ClonoSEQ test of the (11;14) (q13;q32) gene translocation. It is considered positive if a tumor-specific VDJ sequence is detected in the peripheral blood cells by Ig-HTS at a frequency of greater or equal to 1 molecule per 10,000 input leukocyte equivalents of DNA within 1 year post-autologous stem cell transplant (ASCT). The outcome will be reported as number and percent of participants that maintain MRD-negative status (ie, 1-year freedom from MRD). This outcome is reported as a number without dispersion.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants for which molecular residual disease (MRD) disease status assessments were available are included.
Arm/Group Title CpG-MCL Vaccine
Hide Arm/Group Description:

An autologous anti-tumor vaccine.

CpG-MCL vaccine: CpG-MCL vaccine is a vaccine prepared by co-culturing cells from the participant's mantle cell lymphoma suspension with 3 mcg/mL PF-3512676, then irradiated to 200 Gy. 1 x 10e8 CpG-MCL cells will be given as a subcutaneous injection.

PF-3512676: PF-03152676 is a synthetic immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) moledule containing unmethylated cytosine and guanine (CpG) motifs.

Vaccine-primed T-cells: Vaccine primed T-cells are the post-vaccination leukapheresis harvest of peripheral blood mononuclear cells. Each collection is approx 1 x 10e10 CD3+ T-cells.

Autologous hematopoietic stem cell transplant (HSCT): Regular medical procedure

Rituximab: 375 mg/m² by infusion

Standard induction chemotherapy: Patient-specific, regular medical care treatment as determined by treating oncologist

Cyclophosphamide: Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC)

Overall Number of Participants Analyzed 45
Measure Type: Count of Participants
Unit of Measure: Participants
41
  91.1%
2.Secondary Outcome
Title Time-to-progression (TTP)
Hide Description Time-to-progression (TTP) is measured from the time of autologous stem cell transplantation (ASCT) until the cancer progresses or relapses. Progression is assessed based on CT imaging per the Cheson Criteria (2008). Progression per the Cheson Criteria is defined as having occurred when the sum of tumor lesion dimensions is ≥ 150% of the baseline value. The outcome is reported as the median with 95% confidence interval, as determined by Kaplan-Meier analysis and log-rank test.
Time Frame 7.7 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title CpG-MCL Vaccine
Hide Arm/Group Description:

An autologous anti-tumor vaccine.

CpG-MCL vaccine: CpG-MCL vaccine is a vaccine prepared by co-culturing cells from the participant's mantle cell lymphoma suspension with 3 mcg/mL PF-3512676, then irradiated to 200 Gy. 1 x 10e8 CpG-MCL cells will be given as a subcutaneous injection.

PF-3512676: PF-03152676 is a synthetic immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) moledule containing unmethylated cytosine and guanine (CpG) motifs.

Vaccine-primed T-cells: Vaccine primed T-cells are the post-vaccination leukapheresis harvest of peripheral blood mononuclear cells. Each collection is approx 1 x 10e10 CD3+ T-cells.

Autologous hematopoietic stem cell transplant (HSCT): Regular medical procedure

Rituximab: 375 mg/m² by infusion

Standard induction chemotherapy: Patient-specific, regular medical care treatment as determined by treating oncologist

Cyclophosphamide: Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC)

Overall Number of Participants Analyzed 47
Median (95% Confidence Interval)
Unit of Measure: years
6.9 [1] 
(5.92 to NA)
[1]
The upper end of the 95% confidence interval was not reached.
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival (OS) rate is reported as number and percentage of participants remaining alive the date of transplant through each year, up to 5 years (reported as a number without dispersion).
Time Frame After 1, 2, 3, 4, and 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants that received the CpG-MCL Vaccine are included.
Arm/Group Title CpG-MCL Vaccine
Hide Arm/Group Description:

An autologous anti-tumor vaccine.

CpG-MCL vaccine: CpG-MCL vaccine is a vaccine prepared by co-culturing cells from the participant's mantle cell lymphoma suspension with 3 mcg/mL PF-3512676, then irradiated to 200 Gy. 1 x 10e8 CpG-MCL cells will be given as a subcutaneous injection.

PF-3512676: PF-03152676 is a synthetic immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) moledule containing unmethylated cytosine and guanine (CpG) motifs.

Vaccine-primed T-cells: Vaccine primed T-cells are the post-vaccination leukapheresis harvest of peripheral blood mononuclear cells. Each collection is approx 1 x 10e10 CD3+ T-cells.

Autologous hematopoietic stem cell transplant (HSCT): Regular medical procedure

Rituximab: 375 mg/m² by infusion

Standard induction chemotherapy: Patient-specific, regular medical care treatment as determined by treating oncologist

Cyclophosphamide: Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC)

Overall Number of Participants Analyzed 48
Measure Type: Count of Participants
Unit of Measure: Participants
OS after 1 year
42
  87.5%
OS after 2 year
33
  68.8%
OS after 3 year
27
  56.3%
OS after 4 year
19
  39.6%
OS after 5 year
13
  27.1%
4.Secondary Outcome
Title Detection of Tumor-specific CD8-positve Memory T-cells Before and After Vaccination
Hide Description Anti-tumor T-cell immune responses were evaluated by an in vitro evocative test on their peripheral blood mononuclear cell (PBMCs) before and after vaccination, as assessed by measurement of intracellular cytokines and/or intracellular perforin/granzyme in CD8+ T-cells, and/or CD137 induction on CD4+ T-cells. PBMCs were co-cultured with CpG-activated autologous MCL tumor cells and evaluated for tumor-specific immune responses as measured by CD137 expression on their T cells. The outcome is reported as the number of participants for whom tumor-specific memory CD8 cells were detected at baseline and after vaccination and transplant (numbers without dispersion).
Time Frame Baseline and after vaccination and transplant, approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants for which both baseline and post-transplant assessments were available are included.
Arm/Group Title CpG-MCL Vaccine
Hide Arm/Group Description:

An autologous anti-tumor vaccine.

CpG-MCL vaccine: CpG-MCL vaccine is a vaccine prepared by co-culturing cells from the participant's mantle cell lymphoma suspension with 3 mcg/mL PF-3512676, then irradiated to 200 Gy. 1 x 10e8 CpG-MCL cells will be given as a subcutaneous injection.

PF-3512676: PF-03152676 is a synthetic immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) moledule containing unmethylated cytosine and guanine (CpG) motifs.

Vaccine-primed T-cells: Vaccine primed T-cells are the post-vaccination leukapheresis harvest of peripheral blood mononuclear cells. Each collection is approx 1 x 10e10 CD3+ T-cells.

Autologous hematopoietic stem cell transplant (HSCT): Regular medical procedure

Rituximab: 375 mg/m² by infusion

Standard induction chemotherapy: Patient-specific, regular medical care treatment as determined by treating oncologist

Cyclophosphamide: Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC)

Overall Number of Participants Analyzed 35
Measure Type: Count of Participants
Unit of Measure: Participants
At Baseline
31
  88.6%
After Transplant
14
  40.0%
5.Secondary Outcome
Title Detection of Tumor-specific CD4-positve T-cells Before and After Vaccination
Hide Description Anti-tumor T-cell immune responses were evaluated by an in vitro evocative test on their peripheral blood mononuclear cell (PBMCs) before and after vaccination, as assessed by measurement of intracellular cytokines and/or intracellular perforin/granzyme in CD8+ T-cells, and/or CD137 induction on CD4+ T-cells. PBMCs were co-cultured with CpG-activated autologous MCL tumor cells and evaluated for tumor-specific immune responses as measured by CD137 expression on their T cells. The outcome is reported as the number of participants for whom tumor-specific memory CD4 cells were detected at baseline and after transplant (numbers without dispersion).
Time Frame Baseline and after vaccination and transplant, approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants for which both baseline and post-transplant assessments were available are included.
Arm/Group Title CpG-MCL Vaccine
Hide Arm/Group Description:

An autologous anti-tumor vaccine.

CpG-MCL vaccine: CpG-MCL vaccine is a vaccine prepared by co-culturing cells from the participant's mantle cell lymphoma suspension with 3 mcg/mL PF-3512676, then irradiated to 200 Gy. 1 x 10e8 CpG-MCL cells will be given as a subcutaneous injection.

PF-3512676: PF-03152676 is a synthetic immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) moledule containing unmethylated cytosine and guanine (CpG) motifs.

Vaccine-primed T-cells: Vaccine primed T-cells are the post-vaccination leukapheresis harvest of peripheral blood mononuclear cells. Each collection is approx 1 x 10e10 CD3+ T-cells.

Autologous hematopoietic stem cell transplant (HSCT): Regular medical procedure

Rituximab: 375 mg/m² by infusion

Standard induction chemotherapy: Patient-specific, regular medical care treatment as determined by treating oncologist

Cyclophosphamide: Regular medical care treatment to mobilize peripheral blood progenitor cell (PBPC)

Overall Number of Participants Analyzed 35
Measure Type: Count of Participants
Unit of Measure: Participants
At Baseline
20
  57.1%
After Transplant
14
  40.0%
Time Frame 3 months
Adverse Event Reporting Description

The study has 2 stages, ie, procedures preceding vaccine administration + the vaccine treatment period.

  • All cause mortality includes the entire subject population (ie, both pre-vaccine period and actual treatment period).
  • Serious Adverse Events and Other (Not Including Serious) Adverse Events information includes only the participants that received the vaccine and transplant (actual study treatment period).
 
Arm/Group Title CpG-MCL Vaccine
Hide Arm/Group Description An autologous anti-tumor vaccine.
All-Cause Mortality
CpG-MCL Vaccine
Affected / at Risk (%)
Total   19/59 (32.20%)    
Hide Serious Adverse Events
CpG-MCL Vaccine
Affected / at Risk (%) # Events
Total   31/48 (64.58%)    
Blood and lymphatic system disorders   
Blood and lymphatic system disorders - Other, Graft failure  1  1/48 (2.08%)  1
Febrile Neutropenia  1  1/48 (2.08%)  1
Neutrophils/granulocytes (ANC/AGC)  1  1/48 (2.08%)  2
Platelets  1  1/48 (2.08%)  1
General disorders   
Death NOS  1  2/48 (4.17%)  2
Infections and infestations   
Infection, dental abscess  1  1/48 (2.08%)  1
Investigations   
Leukocytes (total WBC)  1  2/48 (4.17%)  2
Musculoskeletal and connective tissue disorders   
Myositis  1  1/48 (2.08%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Death Disease progression  1  12/48 (25.00%)  12
Nervous system disorders   
Hemorrhage, CNS, Intracranial hemorrhage  1  1/48 (2.08%)  1
Respiratory, thoracic and mediastinal disorders   
Adult Respiratory Distress Syndrome (ARDS)  1  1/48 (2.08%)  1
Pneumonitis  1  4/48 (8.33%)  4
Skin and subcutaneous tissue disorders   
Burn  1  1/48 (2.08%)  1
Vascular disorders   
Thrombosis/embolism  1  1/48 (2.08%)  1
Supraventricular and nodal arrhythmia  1  1/48 (2.08%)  1
1
Term from vocabulary, CTCAE v3.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
CpG-MCL Vaccine
Affected / at Risk (%) # Events
Total   48/48 (100.00%)    
Blood and lymphatic system disorders   
Febrile neutropenia  1  2/48 (4.17%)  2
Leukocytes count low  1  3/48 (6.25%)  3
Lymphocytes count low  1  1/48 (2.08%)  1
Platelets count low  1  2/48 (4.17%)  2
Gastrointestinal disorders   
Abdomen NOS  1  1/48 (2.08%)  1
Anorexia  1  4/48 (8.33%)  7
Diarrhea  1  4/48 (8.33%)  5
Distension/bloating Abdominal (Gas/indigestion)  1  1/48 (2.08%)  2
Heartburn/dyspepsia  1  5/48 (10.42%)  6
Mucositis/Stomatitis  1  1/48 (2.08%)  1
Nausea  1  3/48 (6.25%)  4
Vomiting  1  2/48 (4.17%)  2
General disorders   
Fatigue  1  25/48 (52.08%)  53
Fever  1  29/48 (60.42%)  63
Flu-like syndrome: General  1  4/48 (8.33%)  4
Injection site reaction/extravasation changes: Erythema  1  47/48 (97.92%)  123
Injection site reaction/extravasation changes: Pain  1  19/48 (39.58%)  39
Injection site reaction/extravasation changes: Swelling  1  24/48 (50.00%)  63
Injection site reaction/extravasation changes: Warmth  1  17/48 (35.42%)  35
Rigors/Chills  1  22/48 (45.83%)  45
Weight Loss  1  1/48 (2.08%)  1
Infections and infestations   
Metapneumovirus  1  1/48 (2.08%)  1
Investigations   
Neutrophils/granulocytes count low  1  4/48 (8.33%)  4
Musculoskeletal and connective tissue disorders   
Pain Joint (Arthalgia)  1  16/48 (33.33%)  35
Hip pain  1  1/48 (2.08%)  1
Joint Function  1  1/48 (2.08%)  1
Myalgia  1  29/48 (60.42%)  62
Nervous system disorders   
Dizziness  1  3/48 (6.25%)  3
Head/Headache  1  16/48 (33.33%)  26
Imsomnia  1  2/48 (4.17%)  3
Syncope  1  1/48 (2.08%)  1
Psychiatric disorders   
Phantom sensations (sensitivity/crawly feeling on skin)  1  2/48 (4.17%)  2
Respiratory, thoracic and mediastinal disorders   
Cough  1  4/48 (8.33%)  4
nasal congestion  1  1/48 (2.08%)  1
Pneumonitis  1  2/48 (4.17%)  2
Voice changes/dysarthia  1  1/48 (2.08%)  1
Skin and subcutaneous tissue disorders   
Hyperpigmentation  1  2/48 (4.17%)  2
Induration  1  14/48 (29.17%)  21
Other: Granuloma  1  1/48 (2.08%)  1
Other: thinning/fragile skin  1  2/48 (4.17%)  2
Pruritis/Itching  1  12/48 (25.00%)  15
Rash/Desquamation  1  6/48 (12.50%)  6
Vascular disorders   
Thrombosis  1  1/48 (2.08%)  1
1
Term from vocabulary, CTCAEv 3.0
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Ronald Levy
Organization: Stanford University
Phone: 650-725-6452
EMail: levy@stanford.edu
Publications of Results:
Czerwinski DK, Brody J, Kohrt HE, et al. "Immunotransplant Expands Vaccine Induced Memory T cell Responses In Patients With Mantle Cell Lymphoma." Blood. 2013;122(21)1816.
Chu MP, Brody J, Kohrt HE, et al. "Phase I/II Clinical Trial of CpG Activated Whole Cell Vaccine in Mantle Cell Lymphoma (MCL): Results in Safety and Efficacy from Planned Interim Analysis Blood." Blood. 2015;126(23)
Frank MJ, Khodadoust M, Chu M, et al. "Phase I/II Clinical trial of an activated whole tumor cell vaccine followed by transfer of immune T cells in patients with Mantle Cell Lymphoma." Hematological Oncology). 7 June 2017, https://doi.org/10.1002/hon.2438_72.
Layout table for additonal information
Responsible Party: Ronald Levy, Stanford University
ClinicalTrials.gov Identifier: NCT00490529    
Other Study ID Numbers: IRB-05089
LYMNHL0040-BMT212 ( Other Identifier: OnCore )
96940 ( Other Identifier: Stanford University Alternate IRB Approval Number )
NCI-2011-00136 ( Other Identifier: NCI Trial ID )
First Submitted: June 20, 2007
First Posted: June 22, 2007
Results First Submitted: November 13, 2019
Results First Posted: January 13, 2020
Last Update Posted: January 13, 2020