A Personalized Neoantigen Cancer Vaccine in Treatment Naïve, Asymptomatic Patients With IGHV Unmutated CLL.

NCT03219450 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 17-105
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying a novel type of CLL vaccine as a possible treatment for chronic lymphocytic leukemia (CLL) The names of the study interventions involved in this study are:

• Personalized NeoAntigen Vaccine
• Poly-ICLC
• Cyclophosphamide
• Pembrolizumab

Conditions

Lymphocytic Leukemia

Keywords

Leukemia; Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (3)

• Feasibility of neoantigen identification

  The proportion of all enrolled patients for whom sequencing and analysis leads to identification of at least 7 actionable peptides to initiate vaccine production

  6 months

• Feasibility of vaccine generation

  Of the patients who generate at least 7 actionable peptides, the proportion for whom the time from sample collection to vaccine availability is less than 12 weeks

  6 months

• Safety of NeoVax

  The number of patients with treatment-limiting toxicities based on NCI CTCAE v5.0

  1 year

Study Arms (3)

NeoVax

EXPERIMENTAL

* NeoVax will be administered in a priming and booster phase. * The priming shots will comprise days 1, 4, 8, 15, and 22. * Booster shots will be given on days 78 and 134.

Drug: NeoVax

Neovax + Low-dose cyclophosphamide

EXPERIMENTAL

* NeoVax will be administered in a priming and booster phase. * The priming shots will comprise days 1, 4, 8, 15, and 22. * Booster shots will be given on days 78 and 134. * Low dose cyclophosphamide is administered twice daily on weeks -2, 1, 3, 5

Drug: NeoVax; Drug: Cyclophosphamide

Neovax + Low-dose cyclophosphamide + Pembrolizumab

EXPERIMENTAL

* NeoVax will be administered in a priming and booster phase. * The priming shots will comprise days 1, 4, 8, 15, and 22. * Booster shots will be given on days 78 and 134. * Low dose cyclophosphamide is administered twice daily on weeks -2, 1, 3, 5 * Pembrolizumab will be administered starting on Week 12 Day 78 and for up to 17 cycles (approximately 1 year).

Drug: NeoVax; Drug: Cyclophosphamide; Drug: Pembrolizumab

Interventions

NeoVax DRUG

It stimulates the immune system to attack cancer cells.

Also known as: Neoantigen vaccine

NeoVax; Neovax + Low-dose cyclophosphamide; Neovax + Low-dose cyclophosphamide + Pembrolizumab

Cyclophosphamide DRUG

It is a chemotherapy drug used to treat many cancers. At low doses, it is an investigational drug to help the immune cells to be better at attacking cancer cells while avoiding chemotherapy toxicity.

Also known as: Cytoxan

Neovax + Low-dose cyclophosphamide; Neovax + Low-dose cyclophosphamide + Pembrolizumab

Pembrolizumab DRUG

Is a monoclonal antibody that helps the immune cells to be better at attacking cancer cells.

Also known as: Keytruda

Neovax + Low-dose cyclophosphamide + Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Diagnosis of CLL as per IWCLL 2018 criteria
• Patient's CLL must have an unmutated immunoglobulin heavy chain variable (IGHV) region gene, defined as \< 2% mutated compared to germline.
• Patient must have had no history of CLL-directed therapy due to meeting IWCLL 2018 criteria; no present indication for treatment by iwCLL 2018 criteria; and in the opinion of the treating investigator be anticipated not to require CLL-directed treatment within the next 6 months.
• Patient must have measurable disease (absolute lymphocyte count \> 10K/uL or total white blood cell count ≥ 20K/uL of peripheral blood).
• Patient must have had at least two other absolute lymphocyte counts (ALC) measured since diagnosis of CLL that are at least 2 weeks apart and at least 2 months prior to the one used for initial registration.
• Age ≥ 18 years.
• ECOG performance status 0 or 1
• Participants must have normal organ and marrow function as defined below:
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
• absolute neutrophil count ≥1000 cells/μL
• The effects of NeoVax and poly-ICLC on the developing human fetus are unknown. For this reason, women of childbearing potential (WOCBP) must have a negative pregnancy test (minimum sensitivity 25 IU/L or equivalent of HCG) before entry onto the trial and within 7 days prior to start of study medication. It is the investigators' responsibility to repeat the pregnancy test should start of treatment be delayed.
• Female patients enrolled in the study, who are not free from menses for \>2 years, post hysterectomy / oophorectomy, or surgically sterilized, must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from sexual activity throughout the study, starting with visit 1 through 4 weeks after the last dose of study therapy. Approved contraceptive methods include for example; intra uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception.
• Patient is agreeable to allow tumor (from peripheral blood) and normal tissue (from saliva) samples to be submitted for complete exome and transcriptome sequencing.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Prior therapy for CLL that met IW-CLL treatment criteria, including chemotherapy, targeted therapies (e.g. that antagonize B cell receptor signaling), or immunotherapy (including but not limited to monoclonal antibodies); or radiotherapy or hormonal therapy within the last 2 years of screening registration.
• Participants who are receiving any other investigational agents.
• Previous bone marrow or stem cell transplant
• Concomitant therapy with immunosuppressive or immunomodulatory agents; chronic use of systemic corticosteroids. Previous history of corticosteroid use is acceptable. Use of corticosteroids after initial registration is acceptable if tapered at least one week before NeoVax administration.
• Use of a non-oncology vaccine therapy for prevention of infectious diseases within 2 weeks of any NeoVax administration.
• History of severe allergic reactions attributed to any vaccine therapy for the prevention of infectious diseases.
• Participants who have never received the tetanus vaccine.
• Active, known, or suspected autoimmune disease or immunosuppressive conditions with the exception of vitiligo, type 1 diabetes, residual autoimmune-related hypothyroidism requiring hormone replacement, or psoriasis not requiring systemic treatment.
• Uncontrolled autoimmune cytopenia.
• No lymph node \> 5 cm by CT scan (measured as long axis).
• Del(17p) by fluorescence in situ hybridization in ≥ 10% of CLL cells analyzed
• Any documented transformation of CLL (i.e. Richter's Syndrome).
• Lymphocyte doubling time (LDT) \< 6 months in patients with WBC \> 30,000/uL. Factors contributing to lymphocytosis other than CLL (e.g. infections) should be excluded when calculating the LDT1.
• Serum immunoglobulin level \<400 mg/dL or currently requiring chronic intravenous immunoglobulin G (IVIG)
• Known chronic infections with HIV, hepatitis B or C (see Study Calendar in Section 10 for screening assays).

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Oncovir, Inc.: collaborator
• BioNTech SE: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphoid; Leukemia

Interventions

Cyclophosphamide; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Inhye Ahn, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oriol Olive Noguer

CONTACT

617-632-2581; Oriol_Olive@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 6, 2017
• First Posted: July 17, 2017
• Study Start: August 18, 2021
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)