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

NCT00490529 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB-05089LYMNHL0040-BMT21296940NCI-2011-00136
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma, Mantle-Cell

Outcome Measures

Primary Outcomes (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.

  12 months

Secondary Outcomes (4)

• Time-to-progression (TTP)

  7.7 years

• Overall Survival (OS)

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

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

  Baseline and after vaccination and transplant, approximately 5 years

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

  Baseline and after vaccination and transplant, approximately 5 years

Study Arms (1)

CpG-MCL Vaccine

EXPERIMENTAL

An autologous anti-tumor vaccine.

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

Interventions

CpG-MCL vaccine 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.

Also known as: CpG-activated, autologous tumor vaccine, Cytosine-Guanosine repeats (CpG)-mantle cell lymphoma (CpG-MCL vaccine)

CpG-MCL Vaccine

PF-3512676 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.

Also known as: CPG-7909

CpG-MCL Vaccine

Vaccine-primed T-cells 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.

CpG-MCL Vaccine

Autologous hematopoietic stem cell transplant (HSCT) PROCEDURE

Regular medical procedure

Also known as: Autologous peripheral blood progenitor cell (PBPC) transplant, Autologous peripheral blood stem cell (PBSC) transplant

CpG-MCL Vaccine

Rituximab DRUG

375 mg/m² by infusion

Also known as: Rituxan, hera

CpG-MCL Vaccine

Standard induction chemotherapy DRUG

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

CpG-MCL Vaccine

Cyclophosphamide DRUG

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

Also known as: Cytoxtan, Neosar, CYT, CTX, CPM

CpG-MCL Vaccine

Filgrastim DRUG

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

Also known as: G-CSF, Neupogen

CpG-MCL Vaccine

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ronald Levy: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Related Publications (5)

• 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.

  PMID: 18812472 BACKGROUND

• 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.

  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)

  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.

  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.

  PMID: 32558897 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

ProMune; Transplantation; Rituximab; Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Ronald Levy
• Organization: Stanford University

levy@stanford.edu

650-725-6452

Study Officials

• Ronald Levy, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 20, 2007
• First Posted: June 22, 2007
• Study Start: August 1, 2009
• Primary Completion: December 14, 2017
• Study Completion: December 14, 2017
• Last Updated: January 13, 2020
• Results First Posted: January 13, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)