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Personalized Vaccine in Treating Participants With Smoldering Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT03631043
Recruitment Status : Recruiting
First Posted : August 15, 2018
Last Update Posted : March 5, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This early phase I trial studies the side effects of personalized vaccine in treating participants 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.

Condition or disease Intervention/treatment Phase
Smoldering Plasma Cell Myeloma Procedure: Biopsy Specimen Radiography Biological: Vaccine Therapy Early Phase 1

Detailed 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. To identify shared human leukocyte antigen (HLA) class I-restricted antigens that can be targeted with immunotherapy.

OUTLINE:

Participants undergo collection of blood and bone marrow for making the vaccine. Participants then receive personalized vaccine subcutaneously (SC) on days 1 and 15 of courses 1-2 and on day 1 of courses 3-6. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 3 and 12 months.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Personalized Vaccine for the Immune Prevention of Multiple Myeloma
Actual Study Start Date : December 21, 2018
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : September 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: X-Rays

Arm Intervention/treatment
Experimental: Treatment (personalized vaccine)
Participants undergo collection of blood and bone marrow for making the vaccine. Participants then receive personalized vaccine SC on days 1 and 15 of courses 1-2 and on day 1 of courses 3-6. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Procedure: Biopsy Specimen Radiography
Undergo collection of blood and bone marrow
Other Names:
  • Biospecimen Radiography
  • Specimen Radiography

Biological: Vaccine Therapy
Given personalized vaccine SC




Primary Outcome Measures :
  1. Feasibility assessed by the proportion of participants for whom the vaccine is successfully developed and ready to administer [ Time Frame: Within 12 weeks ]
  2. Incidence of adverse events [ Time Frame: Up to 12 months ]

Secondary Outcome Measures :
  1. Intensity and longevity of antigen specific T-cell mediated immune responses to the neoantigen vaccine [ Time Frame: Up to 12 months ]
  2. Time to progression [ Time Frame: Up to 18 months ]
  3. Duration of response [ Time Frame: Up to 12 months ]
  4. Clinical benefit rate (minor response or better) assessed by the modified International Myeloma Working Group criteria for multiple myeloma [ Time Frame: After 6 courses (168 days) ]
  5. Overall survival [ Time Frame: Up to 12 months ]

Other Outcome Measures:
  1. Rate of minimal residual disease negativity at complete remission assessed based on bone marrow aspirates [ Time Frame: Up to 12 months ]
  2. Molecular and cellular profiling [ Time Frame: Up to 12 months ]
  3. Immunophenotypic analysis [ Time Frame: Up to 12 months ]
    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.

  4. Identification of shared human leukocyte antigen class I-restricted antigens that can be targeted with immunotherapy [ Time Frame: Up to 12 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients with intermediate or high-risk 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): (1) >= 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) (2) 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 1) 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) 2) Renal Insufficiency: creatinine clearance < 40 ml/min or serum creatinine > 2 mg/dL 3) Anemia: hemoglobin value < 10 g/dL 4) 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. a) Bisphosphonates are permitted. b) Treatment with corticosteroids is not permitted (allowed for physiologic doses). c) Radiotherapy is not permitted. d) 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03631043


Contacts
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Contact: Elisabet Manasanch 713-729-2860 eemanasanch@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Elisabet E. Manasanch    713-729-2860    eemanasanch@mdanderson.org   
Principal Investigator: Elisabet E. Manasanch         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Elisabet Manasanch M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03631043     History of Changes
Other Study ID Numbers: 2018-0345
NCI-2018-01614 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2018-0345 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: August 15, 2018    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Smoldering Multiple Myeloma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Precancerous Conditions
Hypergammaglobulinemia
Vaccines
Immunologic Factors
Physiological Effects of Drugs