Dendritic Cell DKK1 Vaccine for Monoclonal Gammopathy and Stable or Smoldering Myeloma

NCT03591614 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: CASE1A16
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to study the safety and preliminary efficacy of a dendritic cell DKK1 vaccine against myeloma. Dendritic cells are immune cells that are collected from the blood of the patient at Case Western Reserve Medical Center and then brought into contact with DKK1, a molecule that is present of myeloma cells but not to a significant amount on other cells except for the prostate and the placenta. It is an investigational (experimental) vaccine that based on studies in the laboratory and in mice is expected to work by presentation of DKK1 to anticancer immune cells via dendritic cells leading to an immune attack on myeloma cells. It is experimental because it is not approved by the Food and Drug Administration (FDA).

Conditions

Monoclonal Gammopathy; Smoldering Myeloma; Myeloma

Keywords

Vaccine; DKK1

Outcome Measures

Primary Outcomes (1)

• Number of patients with dose limiting toxicity

  Toxicity will be assessed according to CTCAE v.4.03. Patients will have weekly CBC w. Differential, CMP, history, and physical. DLT will be defined as any vaccine related non-hematologic toxicity, neutropenia, anemia or thrombocytopenia \> grade 3 that does not resolve to grade \< 2 within 7 days.

  Up to 1 year

Secondary Outcomes (5)

• Average time of progression-free survival

  Up to 1 year

• Average time of overall survival

  Up to 1 year

• Average time to progression

  Up to 1 year

• Best overall response

  Up to 1 year

• Clinical Benefit Response

  Up to 1 year

Study Arms (1)

Dendritic cell DKK1 vaccine

EXPERIMENTAL

5-10x106 DKK1 loaded dendritic cells. Three doses will be given two weeks apart, followed by 11 months of observations.

Biological: DKK1

Interventions

DKK1 BIOLOGICAL

The investigational agent is a DKK1 peptide-loaded autologous dendritic cell vaccine dispensed at a dose of 5-10x106 in 0.5 mL Plasma-Lyte A + 5% HSA.

Dendritic cell DKK1 vaccine

Eligibility Criteria

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

You may qualify if:

• At any time prior to enrollment subjects must have IgG, IgA, kappa, or lambda monoclonal gammopathy confirmed in at least two assessments at least three months apart or histologically confirmed multiple myeloma or carry a diagnosis of smoldering myeloma based on prior documentation of serum m-spike (IgG or IgA) of at least 3g/dL serum m-spike (IgG or IgA) or 24h urine m-spike of at least 500mg/24h.
• Within 28 days prior to enrollment persistence of the clonal plasma cell disorder must be documented by presence of a clonal band on immunofixation of blood or urine or an abnormal serum free kappa/lambda ratio.
• Subjects with myeloma related organ dysfunction must have received prior therapy, reached at least partial remission with at least one of any number of prior regimens, and be candidates for observation off myeloma therapy based on lack of progression at least stable disease for at least 90 days prior to at study entry.
• Performance status ECOG performance status ≤ 2.
• Subjects must have laboratory test results within the following ranges:
• Hemoglobin ≥ 9.0 g/dl
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Total bilirubin \< 2.5 x institutional upper limit of normal
• AST (SGOT) ≤ 2.5 X institutional upper limit of normal
• ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
• Calculated creatinine clearance (Cockcroft-Gault) ≥ 30ml/min
• Anti-myeloma treatment with proteasome inhibitors, IMiDsTM, corticosteroids, low dose cyclophosphamide (≤ 50mg per day) must have been discontinued at least 14 days prior to study entry. Conventional chemotherapy at conventional doses including cyclophosphamide at \> 50mg per day must have been discontinued at least 28 days prior to study entry. At least 180 days must have passed since high dose chemotherapy used in the context of autologous stem cell transplantation. Prior radiation must have been completed at least 14 days prior to enrollment.
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Subjects receiving any other investigational agents.
• Concurrent use of any plasma cell directed therapy including corticosteroids (use of bisphosphonates is allowed).
• Subjects who have previously received an allogeneic stem cell transplant.
• Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection (including active HIV or hepatitis), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Women with childbearing potential (last menstrual period within less than 24 months unless hysterectomy or bilateral oophorectomy has been performed since) as well as pregnant women are excluded from this study because DKK1 is expressed in placental tissue and a DKK1 immune response could harm the child. Breastfeeding women are excluded from this study because antibodies made in response to the dendritic cell DKK1 vaccine could enter milk and affect the health of the breastfed child.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (2)

University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Paraproteinemias; Smoldering Multiple Myeloma; Neoplasms, Plasma Cell

Condition Hierarchy (Ancestors)

Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Neoplasms by Histologic Type

Study Officials

• Ehsan Malek, MD

  University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2018
• First Posted: July 19, 2018
• Study Start: December 1, 2023
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2025
• Last Updated: August 18, 2023

Record last verified: 2023-08

Locations

US (2)