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

NCT ID: NCT00490529

Last Updated: 2020-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2017-12-14

Brief 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. This vaccination may prolong the time which patients will stay in remission from their disease.

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.

Conditions

Lymphoma, Mantle-Cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CpG-MCL Vaccine

An autologous anti-tumor vaccine.

Group Type: EXPERIMENTAL

CpG-MCL vaccine

Intervention Type: BIOLOGICAL

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

Intervention Type: BIOLOGICAL

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-cells

Intervention Type: PROCEDURE

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)

Intervention Type: PROCEDURE

Regular medical procedure

Rituximab

Intervention Type: DRUG

375 mg/m² by infusion

Standard induction chemotherapy

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Filgrastim

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: BIOLOGICAL

PF-3512676

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.

Intervention Type: BIOLOGICAL

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.

Intervention Type: PROCEDURE

Autologous hematopoietic stem cell transplant (HSCT)

Regular medical procedure

Intervention Type: PROCEDURE

Rituximab

375 mg/m² by infusion

Intervention Type: DRUG

Standard induction chemotherapy

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

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Filgrastim

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

Intervention Type: DRUG

Other Intervention Names

CpG-activated, autologous tumor vaccine; Cytosine-Guanosine repeats (CpG)-mantle cell lymphoma (CpG-MCL vaccine); CPG-7909; Autologous peripheral blood progenitor cell (PBPC) transplant; Autologous peripheral blood stem cell (PBSC) transplant; Rituxan; hera; Cytoxtan; Neosar; CYT; CTX; CPM; G-CSF; Neupogen

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Ronald Levy

OTHER

Sponsor Role: lead

Responsible Party

Ronald Levy

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ronald Levy, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University Medical Center

Stanford, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 18812472 (View on PubMed)

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.

Reference Type: RESULT

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)

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: DERIVED

PMID: 32558897 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

LYMNHL0040-BMT212

Identifier Type: OTHER

Identifier Source: secondary_id

96940

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2011-00136

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-05089

Identifier Type: -

Identifier Source: org_study_id