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)

Johns Hopkins Medicine

Status and phase: Completed; Phase 2

Conditions: Multiple Myeloma

Treatments: Biological: Filgrastim; Biological: Allogeneic Myeloma Vaccine; Drug: Melphalan; Biological: Activated marrow infiltrating lymphocytes; Drug: Cyclophosphamide; Biological: Autologous stem cell transplant; Procedure: Leukapheresis

Study type: Interventional

Funder types: Other

Identifiers

NCT01045460

NA_00029491 (Other Identifier)

J0997

Details and patient eligibility

About

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.

Enrollment: 36 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 2 patient groups

ASCT + MILs

Experimental group

Description:

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.

Treatment:

Procedure: Leukapheresis

Biological: Autologous stem cell transplant

Drug: Melphalan

Biological: Activated marrow infiltrating lymphocytes

Drug: Cyclophosphamide

Biological: Filgrastim

ASCT + MILs + vaccine

Experimental group

Description:

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.

Treatment:

Procedure: Leukapheresis

Biological: Autologous stem cell transplant

Drug: Melphalan

Biological: Activated marrow infiltrating lymphocytes

Drug: Cyclophosphamide

Biological: Filgrastim

Biological: Allogeneic Myeloma Vaccine