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

Multiple Myeloma Clinical Trial

— aMILs  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01045460
• Other study ID #: J0997
• Secondary ID: NA_00029491
• Status: Completed
• Phase: Phase 2
• Start date: January 15, 2010
• Est. completion date: June 2020

Study information

• Verified date: February 2021
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: June 2020
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• Activated marrow infiltrating lymphocytes
Administered on Days 3 and 4.
• 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.

Biological:
• Filgrastim
Administered post cyclophosphamide daily until leukapheresis.

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

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

Biological:
• Autologous stem cell transplant
Infused on Day 0.

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rates by Blade Criteria	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.	Up to 1 year
Secondary	Progression-free Survival	Median number of months that participants were alive without disease relapse or progression (progression-free survival).	Up to 5 years
Secondary	Overall Survival	Number of participants alive at 5 years (overall survival).	Up to 5 years
Secondary	Feasibility as Measured by Participant Withdrawal or Removal	Number of participants who withdrew or were removed from the study for reasons other than lack of efficacy prior to completion.	Up to 1 year
Secondary	Safety as Measured by Grade 3-5 Adverse Events	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.	Up to 1 year
Secondary	Anti-tumor Immune Response	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	Days 60, 180, and 360
Secondary	The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (RANKL/OPG Ratio)		Days 60, 180, and 360
Secondary	The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Serum C Telopeptide Levels)	Serum C Telopeptide	Days 60, 180, 360
Secondary	The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (bAlkaline Phosphatase Levels)	bAlkaline phosphatase	Days 60, 180, 360
Secondary	The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Osteocalcin Levels)	Osteocalcin	Days 60, 180, 360
Secondary	Effect of aMILs on Clonogenic Myeloma Precursors	• Examine side population of CD19 enriched PBLs throughout study.	Days 60, 180, and 360