Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 (aMILs)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01045460
Recruitment Status : Active, not recruiting
First Posted : January 11, 2010
Results First Posted : October 8, 2019
Last Update Posted : February 5, 2020
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Biological: Activated marrow infiltrating lymphocytes Biological: Allogeneic Myeloma Vaccine Drug: Cyclophosphamide Biological: Filgrastim Procedure: Leukapheresis Drug: Melphalan Biological: Autologous stem cell transplant Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : January 15, 2010
Actual Primary Completion Date : December 2014
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: ASCT + MILs
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4.
Biological: Activated marrow infiltrating lymphocytes
Administered on Days 3 and 4.
Other Names:
  • MILs
  • aMILs

Drug: Cyclophosphamide
Administered at 2.5 g/m^2.
Other Name: Cytoxan

Biological: Filgrastim
Administered post cyclophosphamide daily until leukapheresis.
Other Name: G-CSF

Procedure: Leukapheresis
Performed approximately 12 days post cyclophosphamide. Exact date depends on peripheral blood CD34+ cell counts.
Other Name: Apheresis

Drug: Melphalan
100 mg/m^2/day given on Days -2 and -1.
Other Name: Alkeran

Biological: Autologous stem cell transplant
Infused on Day 0.
Other Name: ASCT

Experimental: ASCT + MILs + vaccine
Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. The allogeneic myeloma vaccine will be administered on Days 21, 60, 180, and 300.
Biological: Activated marrow infiltrating lymphocytes
Administered on Days 3 and 4.
Other Names:
  • MILs
  • aMILs

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

Drug: Cyclophosphamide
Administered at 2.5 g/m^2.
Other Name: Cytoxan

Biological: Filgrastim
Administered post cyclophosphamide daily until leukapheresis.
Other Name: G-CSF

Procedure: Leukapheresis
Performed approximately 12 days post cyclophosphamide. Exact date depends on peripheral blood CD34+ cell counts.
Other Name: Apheresis

Drug: Melphalan
100 mg/m^2/day given on Days -2 and -1.
Other Name: Alkeran

Biological: Autologous stem cell transplant
Infused on Day 0.
Other Name: ASCT




Primary Outcome Measures :
  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 Outcome Measures :
  1. Evaluate Progression-free Survival and Overall Survival [ Time Frame: Up to 5 years ]
    Median number of months that participants were alive (overall survival) and alive without disease relapse or progression (progression-free survival).

  2. 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.

  3. 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.

  4. 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

  5. The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (RANKL/OPG Ratio) [ Time Frame: Days 60, 180, and 360 ]
  6. The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Serum C Telopeptide Levels) [ Time Frame: Days 60, 180, 360 ]
    Serum C Telopeptide

  7. The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (bAlkaline Phosphatase Levels) [ Time Frame: Days 60, 180, 360 ]
    bAlkaline phosphatase

  8. The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Osteocalcin Levels) [ Time Frame: Days 60, 180, 360 ]
    Osteocalcin

  9. Effect of aMILs on Clonogenic Myeloma Precursors [ Time Frame: Days 60, 180, and 360 ]
    • Examine side population of CD19 enriched PBLs throughout study.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT01045460


Locations
Layout table for location information
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Investigators
Layout table for investigator information
Principal Investigator: Ivan Borrello, MD Johns Hopkins University
  Study Documents (Full-Text)

Documents provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT01045460    
Other Study ID Numbers: J0997
NA_00029491 ( Other Identifier: JHMIRB )
First Posted: January 11, 2010    Key Record Dates
Results First Posted: October 8, 2019
Last Update Posted: February 5, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
multiple myeloma
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Neoplasms, Plasma Cell
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
Cyclophosphamide
Melphalan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists