Clinical trial NCT00490529: Phase 1-2 of a CpG-Activated Whole Cell Vaccine Followed by Autologous Immunotransplant for MCL
Official title: Phase 1-2 Study of a CpG-Activated Whole Cell Vaccine Followed by Autologous "Immunotransplant" for Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, Mantle-Cell
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2007-06-22
Enrollment: 59
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Freedom From Molecular Residual Disease (MRD) Post-autologous Stem Cell Transplant (ASCT)
timeFrame: 12 months
Secondary outcomes:
measure: Time-to-progression (TTP)
timeFrame: 7.7 years
measure: Overall Survival (OS)
timeFrame: After 1, 2, 3, 4, and 5 years
measure: Detection of Tumor-specific CD8-positve Memory T-cells Before and After Vaccination
timeFrame: Baseline and after vaccination and transplant, approximately 5 years
measure: Detection of Tumor-specific CD4-positve T-cells Before and After Vaccination
timeFrame: Baseline and after vaccination and transplant, approximately 5 years
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
Study officials:
affiliation: Stanford University
name: Ronald Levy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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)
citation: 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.
citation: 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.