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Completed

NCT Number: NCT01045460

Trial of Activated Marrow Infiltrating Lymphocytes Alone or in Conjunction With an Allogeneic Granulocyte Macrophage Colony-stimulating Factor (GM-CSF)-Based Myeloma Cellular Vaccine in the Autologous Transplant Setting in Multiple Myeloma

Patient Population: Patients with active myeloma (Stage II/III) that have completed induction therapy and are eligible for an autologous stem cell transplant.

Number of Patients: Will treat a total of 32 evaluable patients in a 1:1 randomization of aMILs vs aMILs plus vaccine. An evaluable patient is defined as one which has received the activated MILs and is at least 6 months post-transplant.

Study Objectives:

Disease response as determined by the Blade' criteria will be the primary endpoint of the trial at one year.

Additional study endpoints include progression free survival, parameters of T cell reconstitution, anti-tumor immune responses as well as the effect on osteoclastogenesis and clonogenic myeloma precursor cells.

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Key information

Conditions

Multiple Myeloma Blood Protein Disorders Cardiovascular Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Paraproteinemias Vascular Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Durie-Salmon Stage II or III multiple myeloma
  • Newly diagnosed either prior to receiving treatment or having completed induction therapy
  • Relapsed myeloma not previously transplanted within the past 5 years
  • Measurable serum and/or urine M-protein from prior to induction therapy documented and available. A positive serum free lite assay is acceptable
  • Age greater than 18 years old
  • ECOG performance status of 0 - 2
  • Meet all institutional requirements for autologous stem cell transplantation
  • The patient must be able to comprehend and have signed the informed consent

Exclusion criteria

  • Diagnosis of any of the following plasma cell disorders: POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein] and skin changes) Non-secretory myeloma (no measurable protein on Serum Free Lite Assay)
  • Plasma cell leukemia
  • Amyloidosis
  • Use of corticosteroids (glucocorticoids) within 21 days of pre-transplant vaccine or bone marrow collection
  • Use of any myeloma-specific therapy other than lenalidomide within 21 days of pre-transplant vaccine
  • In a complete remission at the time of bone marrow collection
  • Infection requiring treatment with antibiotics, antifungal, or antiviral agents within seven days of vaccination or bone marrow collection
  • Participation in any clinical trial, within four weeks prior to vaccination or bone marrow collection on this trial, which involved an investigational drug or device
  • History of malignancy other than multiple myeloma within five years of vaccination or bone marrow collection, except adequately treated basal or squamous cell skin cancer
  • Active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosis) requiring systemic treatment. Hypothyroidism without evidence of Grave's Disease or Hashimoto's thyroiditis is permitted
  • Evidence of spinal cord compression at time of transplant

Treatment and study plan

Activated marrow infiltrating lymphocytes

Biological

Administered on Days 3 and 4.

Other names: MILs, aMILs

Allogeneic Myeloma Vaccine

Biological

Allogeneic granulocyte macrophage colony-stimulating factor (GM-CSF)-based myeloma cellular vaccine. Administered on Days 21, 60, 180, and 300.

Cyclophosphamide

Drug

Administered at 2.5 g/m^2.

Other names: Cytoxan

filgrastim

Biological

Administered post cyclophosphamide daily until leukapheresis.

Other names: G-CSF

Leukapheresis

Procedure

Performed approximately 12 days post cyclophosphamide. Exact date depends on peripheral blood CD34+ cell counts.

Other names: Apheresis

melphalan

Drug

100 mg/m^2/day given on Days -2 and -1.

Other names: Alkeran

Autologous stem cell transplant

Biological

Infused on Day 0.

Other names: ASCT

Primary outcomes

  1. Response Rates by Blade Criteria

    Time frame: Up to 1 year

    Number of participants with each disease response category utilizing the Blade criteria:

    • Complete Response (CR): Defined as negative serum and urine immunofixation and a bone marrow aspirate with < 5% plasma cells.
    • Near Complete Response (nCR): Defined as negative serum and urine paraprotein, positive serum and/or urine immunofixation, and a bone marrow aspirate with < 5% plasma cells.
    • Very Good Partial Response (VGPR): Defined as negative serum and urine paraprotein with positive serum and/or urine immunofixation; or a 90% decrease in serum paraprotein with urine paraprotein < 100 mg/24 hours.
    • Partial Response (PR): Defined as a 50-89% decrease in serum paraprotein.
    • Minimal Response (MR): Defined as a 25-49% decrease in serum paraprotein.
    • Stable Disease (SD): Defined as not falling into any other response category.
    • Overall response rate (ORR): Total of CR, nCR, VGPR, and PR.

Secondary outcomes

  1. Progression-free Survival

    Time frame: Up to 5 years

    Median number of months that participants were alive without disease relapse or progression (progression-free survival).

  2. Overall Survival

    Time frame: Up to 5 years

    Number of participants alive at 5 years (overall survival).

  3. Feasibility as Measured by Participant Withdrawal or Removal

    Time frame: Up to 1 year

    Number of participants who withdrew or were removed from the study for reasons other than lack of efficacy prior to completion.

  4. Safety as Measured by Grade 3-5 Adverse Events

    Time frame: Up to 1 year

    Number of participants who experienced at least one grade 3-5 adverse event by CTCAE 3.0 that was attributed to MILs or the myeloma vaccine.

  5. Anti-tumor Immune Response

    Time frame: Days 60, 180, and 360

    • Evaluate tumor specific responses in blood and bone marrow
    • Examine T cell responses to DC-pulsed myeloma cell lines
    • Examine induction of novel antibody responses

  6. The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (RANKL/OPG Ratio)

    Time frame: Days 60, 180, and 360

  7. The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Serum C Telopeptide Levels)

    Time frame: Days 60, 180, 360

    Serum C Telopeptide

  8. The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (bAlkaline Phosphatase Levels)

    Time frame: Days 60, 180, 360

    bAlkaline phosphatase

  9. The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Osteocalcin Levels)

    Time frame: Days 60, 180, 360

    Osteocalcin

  10. Effect of aMILs on Clonogenic Myeloma Precursors

    Time frame: Days 60, 180, and 360

    • Examine side population of CD19 enriched PBLs throughout study.

Sponsors and collaborators

Lead sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Other

Registry information

Official study title

Randomized Trial of Activated Marrow Infiltrating Lymphocytes Alone or in Conjunction With an Allogeneic GM-CSF-based Myeloma Cellular Vaccine in the Autologous Transplant Setting in Multiple Myeloma

Acronym: aMILs

Important dates

Study start
2010
Primary completion
2014
Study completion
2020
First posted
Jan 11, 2010
Registry last updated
Apr 9, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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