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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03631043
Other study ID # 2018-0345
Secondary ID NCI-2018-0161420
Status Active, not recruiting
Phase Early Phase 1
First received
Last updated
Start date December 21, 2018
Est. completion date September 30, 2025

Study information

Verified date May 2024
Source M.D. Anderson Cancer Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This early phase I trial studies the side effects of personalized vaccine in treating patients with smoldering multiple myeloma. Vaccines made from a person's blood and bone marrow may help the body build an effective immune response to kill cancer cells.


Description:

PRIMARY OBJECTIVES: I. To demonstrate that developing a custom vaccine for smoldering multiple myeloma (SMM) is feasible. II. To show that a custom peptide-based vaccine in smoldering multiple myeloma is safe. SECONDARY OBJECTIVES: I. To determine the intensity and longevity of antigen specific T-cell mediated immune responses to the neoantigen vaccine. II. Time to progression to multiple myeloma (TTM) at the end of the follow up period (18 months). III. Duration of response. IV. Clinical benefit rate (minor response [MR] or better) after 6 cycles of vaccine treatment per modified International Myeloma Working Group (IMWG) criteria for multiple myeloma (MM). V. Overall survival. EXPLORATORY OBJECTIVES: I. Rate of minimal residual disease (MRD) negativity at complete remission (CR), if achieved. MRD assessment will be based on bone marrow aspirates. II. Molecular profiling (including whole exome sequencing, gene expression profiling and ribonucleic acid (RNA) sequencing of tumor/bone marrow samples) and cellular (including flow cytometry) profiling at baseline using bone marrow aspirate samples and peripheral blood. III. Immunophenotypic characterization of dendritic, T-, B-, natural killer (NK)- and NKT-cells, and inhibitory/activation markers on tumor cells at baseline (bone marrow and peripheral blood), day 1 of each cycle (peripheral blood only) and at completion of 6 cycles of therapy (bone marrow and peripheral blood) in bone marrow aspirate samples and/or peripheral blood. IV. Perform mass spectrometry-based proteomics analysis on 15 myeloma cell lines to identify shared human leukocyte antigen (HLA) class I-restricted antigens that can be targeted with immunotherapy. OUTLINE: Patients are assigned to 1 of 2 stages. STAGE I: Patients undergo collection of blood and bone marrow for making the vaccine. Patients then receive personalized vaccine subcutaneously (SC) on days 1 and 15 of cycles 1-2 and on day 1 of cycles 3-6. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. STAGE II: Patients undergo collection of blood and bone marrow for making the vaccine. Patients then receive personalized vaccine SC on days 1 and 15 of cycles 1-2 and on day 1 of cycles 3-6. Patients also receive lenalidomide orally (PO) on days 1-21. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 12 months.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 30
Est. completion date September 30, 2025
Est. primary completion date September 30, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Adult patients with intermediate or high-risk smoldering multiple myeloma (SMM) are eligible - Patients must have histologically confirmed SMM based on the following criteria. Both criteria must be met: (a) Serum monoclonal protein (IgG or IgA) >= 3 g/dL or urinary monoclonal protein >=500 mg per 24 hours and/or clonal bone marrow plasma cells more or equal to 10% (b) Absence of myeloma defining events or amyloidosis - Additionally, patients must meet criteria for intermediate or high risk of progression to multiple myeloma by Programa para el Estudio de la Terapeutica en Hemopatía Maligna (PETHEMA) criteria (patients must have at least 1 risk factors present): - >= 95% abnormal plasma cells/total plasma cells in bone marrow compartment. (This is measured as a percentage of the total abnormal versus normal plasma cells in the bone marrow compartment using standard flow cytometry of the bone marrow aspirate. Having >= 95% abnormal plasma cells/total plasma cells constitutes a risk factor for progression to multiple myeloma by PETHEMA criteria) - Immunoparesis (The patient having low uninvolved immunoglobulins in peripheral blood, for example if a patient has IgA smoldering multiple myeloma, then either having a low IgM and/or low IgG will qualify as a risk factor for progression to multiple myeloma) *1 of 2 risk factors: intermediate risk for progression at a rate of ~50% at 5 years *2 of 2 risk factors: high risk for progression at a rate of 72% at 5 years - Creatinine clearance >= 40 ml/min using the modification of diet in renal disease (MDRD) equation - Eastern Cooperative Oncology Group (ECOG) performance status 0-2 - Absolute neutrophil count (ANC) >= 1.0 x 10^9/L - Hemoglobin >= 10 g/dL - Platelet count >= 50 x 10^9/L - Platelet and blood transfusions are allowed on protocol. Growth factors, including granulocyte colony stimulating factors and erythropoietin are allowed - Bilirubin < 1.5 x the upper limit of normal (ULN) - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x ULN - Subjects must be able to give informed consent Exclusion Criteria: - Evidence of myeloma defining events due to underlying plasma cell proliferative disorder meeting at least one of the following - Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the upper limit of normal or > 2.75 mmol/L (> 11 mg/dL) - Renal Insufficiency: creatinine clearance < 40 ml/min or serum creatinine > 2 mg/dL - Anemia: hemoglobin value < 10 g/dL - Bone lesions: one or more osteolytic lesions on skeletal radiography, computerized tomography (CT) or 2-deoxy-2[F-18] fluoro-D-glucose positron emission tomography CT (PET-CT) - Prior or concurrent systemic treatment for SMM - Bisphosphonates are permitted - Treatment with corticosteroids is not permitted (allowed for physiologic doses) - Radiotherapy is not permitted - Prior treatment for smoldering multiple myeloma with chemotherapy agents approved for the treatment of multiple myeloma is not permitted - Plasma cell leukemia - Pregnant or lactating females - Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment - Has a known history of active TB (Bacillus tuberculosis) - Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer - Has an active infection requiring systemic therapy - Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator - Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial - Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 60 days after the last dose of trial treatment - Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) - Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)

Study Design


Intervention

Procedure:
Biopsy Specimen Radiography
Undergo collection of blood and bone marrow
Drug:
Lenalidomide
Given PO
Biological:
Vaccine Therapy
Given personalized vaccine SC

Locations

Country Name City State
United States M D Anderson Cancer Center Houston Texas

Sponsors (1)

Lead Sponsor Collaborator
M.D. Anderson Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Rate of minimal residual disease negativity at complete remission Assessed based on bone marrow aspirates. Up to 12 months
Other Molecular and cellular profiling Up to 12 months
Other Immunophenotypic analysis Will assess dendritic, T-, B-, natural killer (NK)- and NKT-cells, and inhibitory/activation markers on tumor cells at baseline (bone marrow and peripheral blood), day 1 of each cycle (peripheral blood only) and at completion of 6 cycles of therapy (bone marrow and peripheral blood) in bone marrow aspirate samples and/or peripheral blood. Up to 12 months
Other Identification of shared human leukocyte antigen class I-restricted antigens that can be targeted with immunotherapy Up to 12 months
Primary Feasibility assessed by the proportion of participants for whom the vaccine is successfully developed and ready to administer Within 12 weeks
Primary Incidence of adverse events Up to 12 months
Secondary Intensity and longevity of antigen specific T-cell mediated immune responses to the neoantigen vaccine Up to 12 months
Secondary Time to progression Up to 18 months
Secondary Duration of response Up to 12 months
Secondary Clinical benefit rate (minor response or better) Assessed by the modified International Myeloma Working Group criteria for multiple myeloma. After 6 cycles (168 days)
Secondary Overall survival Up to 12 months
See also
  Status Clinical Trial Phase
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Active, not recruiting NCT04370483 - Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma Early Phase 1
Terminated NCT02353572 - Melphalan and Bortezomib Prior to Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma Phase 1/Phase 2
Recruiting NCT05014646 - Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma in African-American and European-American Patients Phase 2
Active, not recruiting NCT05288062 - Immunomodulatory Drugs (Lenalidomide With or Without Pomalidomide) in Combination With a Corticosteroid Drug (Dexamethasone) for the Treatment of Multiple Myeloma Phase 2
Recruiting NCT05136807 - Quality of Life in Patients With Asymptomatic Monoclonal Gammopathies
Recruiting NCT05312255 - Non-chemotherapeutic Interventions for the Improvement of Quality of Life and Immune Function in Patients With Multiple Myeloma N/A
Active, not recruiting NCT02603887 - Pembrolizumab in Treating Patients With Intermediate or High-Risk Smoldering Multiple Myeloma Early Phase 1
Active, not recruiting NCT02960555 - Isatuximab With or Without Lenalidomide in Patients With High Risk Smoldering Multiple Myeloma (ISAMAR) Phase 2
Recruiting NCT02726750 - Observational Prospective Research Study In Monoclonal Gammopathies leadINg to Myeloma
Withdrawn NCT03952832 - Leflunomide in Treating Patients With High-Risk Smoldering Multiple Myeloma Phase 2
Recruiting NCT04776395 - Iberdomide Alone or in Combination With Dexamethasone for the Treatment of Intermediate- or High-Risk Smoldering Multiple Myeloma Phase 2
Completed NCT02492750 - Lenalidomide and Dexamethasone With or Without Anakinra in Treating Patients With Early Stage Multiple Myeloma Phase 1