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Lymphoma, Mantle-CellPhase 2NCT00490529

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

A Phase 2 study testing CpG-MCL vaccine, PF-3512676 and Vaccine-primed T-cells in people with Lymphoma, Mantle-Cell, run by Ronald Levy at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Mantle cell lymphoma (MCL) is a sub-type of non-Hodgkin's lymphoma (NHL) which is generally considered incurable with current therapy. Participants will receive an autologous vaccine against their individual lymphoma after undergoing stem cell transplantation. Read more about this study

Who is it for?
Ages 21 to 70 years
Conditions the study is for
Lymphoma, Mantle-Cell
What is being tested?
CpG-MCL vaccine, PF-3512676 and Vaccine-primed T-cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
1 siteUnited States
Study dates
Aug 2009to 14 Dec 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Newly-diagnosed with mantle cell lymphoma (MCL) with accessible disease site for excisional biopsy, OR have sufficient peripheral blood tumor to leukapherese ≥ 1.5 x 10e9 lymphoma cells in a single session
  • Medically appropriate by standard clinical criteria to receive rituximab and standard induction chemotherapy and high-dose chemotherapy with autologous hematopoietic cell transplant (AHCT)
  • HIV-negative
  • Eastern Cooperative Oncology Group (ECOG) Performance Status, OR Karnofsky performance scale 50 to 100%
  • Capable of providing informed consent

Who cannot join

  • Currently receiving immunosuppressive medications
  • Severe psychological or medical illness
  • Pregnant or lactating
  • Unable to safely complete the study, at the discretion of the principal investigator

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Stanford University Medical Center

    Stanford, California, 94305

Other trials in United States

About this study

Official title: Phase 1-2 Study of a CpG-Activated Whole Cell Vaccine Followed by Autologous "Immunotransplant" for Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a sub-type of non-Hodgkin's lymphoma (NHL) which is generally considered incurable with current therapy. Participants will receive an autologous vaccine against their individual lymphoma after undergoing stem cell transplantation. This vaccination may prolong the time which patients will stay in remission from their disease.

Read the detailed description

Study treatment is a complex set of steps of research procedures and regular medical care. By using a participant's cancer cells as an immungen, the study hopes to improve freedom from molecular residual disease (MRD).

PRIMARY OBJECTIVE Freedom from molecular residual disease at 1-year post-autologous transplant.

SECONDARY OBJECTIVE Time To Clinical Progression (TTP)

This study has 2 research agents, PF-03152676 and CpG-MCL Vaccine.

PF-03152676 is a synthetic DNA molecule, 24 nucleotides in length with a nuclease-resistant phosphorothioate backbone. It is an immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) containing unmethylated cytosine and guanine (CpG) motifs and synthesized with a nuclease-resistant phosphorothioate backbone. PF-03512676 acts as an agonist of human Toll-like receptor 9, leading to activation of antigen-presenting cells and a cascade of anti-tumor immune reactions.

CpG-MCL Vaccine is the primary study agent. It is prepared by dissociating a participant's harvested tumor cells into a single-cell suspension, and culturing them with PF-03152676 for 72 hours at 37 degrees C, 5% CO2 to allow for up-regulation of antigen-presenting and co-stimulatory molecules, then irradiated to 200 Gy to destroy any remaining cancer propagating ability.

The study procedure is summarized as 12 steps, listed below.

  • Step 1. Undergo excisional tumor biopsy or apheresis to obtain tumor cells, which will be used to generate the CpG-MCL vaccine .
  • Step 2. Receive standard induction chemotherapy (regular medical care).
  • Step 3. Once in remission, receive 3 vaccinations of CpG-MCL Vaccine over 3 weeks. With each CpG-MCL vaccination, a concurrent subcutaneous injection of PF-3512676 is administered as an adjuvant.
  • Step 4. About 4 weeks later, receive rituximab 375 mg/m² to minimize any residual tumor.
  • Step 5. Apheresis procedure to harvest the CpG-MCL Vaccine-primed T-cells. Each collection is ~1 x 10e10 CD3+ T-cells.
  • Step 6. High-dose cytoxan and filgrastim to mobilize peripheral blood progenitor cell (PBPC).
  • Step 7. Undergo separate apheresis procedure to harvest PBPC).
  • Step 8. Receive myeloablative chemotherapy (regular medical care).
  • Step 9. Receive PBPC infusion (also known as autologous hematopoietic cell transplant, AHCT).
  • Step 10. Within 3 days of AHCT (but typically 1 day), receive infusion of CpG-MCL Vaccine-primed T-cells, followed within 1 hour by a with 4th vaccination with CpG-MCL Vaccine (1st booster vaccination).
  • Step 11. After hematopoietic recovery, receive 5th vaccination with CpG-MCl (2nd booster vaccination).
  • Step 12. Monitor participants for general health and disease status through at least 3 years.
Being tested
CpG-MCL vaccine, PF-3512676, Vaccine-primed T-cells, Autologous hematopoietic stem cell transplant (HSCT), Rituximab
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CpG-MCL vaccineBiological

    Also called CpG-activated, autologous tumor vaccine, Cytosine-Guanosine repeats (CpG)-mantle cell lymphoma (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-3512676Biological

    Also called CPG-7909

    PF-03152676 is a synthetic immunostimulatory, single-stranded oligodeoxynucleotide (oligo-DNA) moledule containing unmethylated cytosine and guanine (CpG) motifs. PF-03512676 acts as an agonist of human Toll-like receptor 9, leading to activation of antigen-presenting cells and a cascade of antitumor immune reactions.

  • Vaccine-primed T-cellsProcedure or surgery

    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)Procedure or surgery

    Also called Autologous peripheral blood progenitor cell (PBPC) transplant, Autologous peripheral blood stem cell (PBSC) transplant

    Regular medical procedure

  • RituximabDrug

    Also called Rituxan, hera

    375 mg/m² by infusion

  • Standard induction chemotherapyDrug

    Patient-specific, regular medical care treatment as determined by treating oncologist

  • CyclophosphamideDrug

    Also called Cytoxtan, Neosar, CYT, CTX

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

  • FilgrastimDrug

    Also called G-CSF, Neupogen

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

Study groups in NCT00490529
Study groupRoleWhat they receive
CpG-MCL VaccineExperimentalAn autologous anti-tumor vaccine.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Freedom From Molecular Residual Disease (MRD) Post-autologous Stem Cell Transplant (ASCT)

    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.

    Measured: 12 months

Secondary outcomes (4)

  1. Time-to-progression (TTP)

    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.

    Measured: 7.7 years

  2. Overall Survival (OS)

    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).

    Measured: After 1, 2, 3, 4, and 5 years

  3. Detection of Tumor-specific CD8-positve Memory T-cells Before and After Vaccination

    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).

    Measured: Baseline and after vaccination and transplant, approximately 5 years

  4. Detection of Tumor-specific CD4-positve T-cells Before and After Vaccination

    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).

    Measured: Baseline and after vaccination and transplant, approximately 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jun 2007 (estimated)
  2. Study startAug 2009
  3. Primary completion14 Dec 2017
  4. Study completion14 Dec 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00490529
Sponsor's protocol ID
IRB-05089
Other IDs
LYMNHL0040-BMT212, 96940, NCI-2011-00136
Status last verified
Jan 2020
First submitted
20 Jun 2007
Last updated
13 Jan 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Brody JD, Goldstein MJ, Czerwinski DK, Levy R. Immunotransplantation preferentially expands T-effector cells over T-regulatory cells and cures large lymphoma tumors. Blood. 2009 Jan 1;113(1):85-94. doi: 10.1182/blood-2008-05-155457. Epub 2008 Sep 23.

    PubMed 18812472

  • 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.

  • Frank MJ, Khodadoust MS, Czerwinski DK, Haabeth OAW, Chu MP, Miklos DB, Advani RH, Alizadeh AA, Gupta NK, Maeda LS, Reddy SA, Laport GG, Meyer EH, Negrin RS, Rezvani AR, Weng WK, Sheehan K, Faham M, Okada A, Moore AH, Phillips DL, Wapnir IL, Brody JD, Levy R. Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial. J Exp Med. 2020 Sep 7;217(9):e20191712. doi: 10.1084/jem.20191712.

    PubMed 32558897

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CpG-MCL vaccine, PF-3512676 and Vaccine-primed T-cells in people with Lymphoma, Mantle-Cell, run by Ronald Levy at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Freedom From Molecular Residual Disease (MRD) Post-autologous Stem Cell Transplant (ASCT) (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00490529, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2020.

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