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

NCT ID: NCT01045460

Last Updated: 2021-04-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-15
• Study Completion Date: 2020-06-30

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Activated marrow infiltrating lymphocytes

Intervention Type: BIOLOGICAL

Administered on Days 3 and 4.

Cyclophosphamide

Intervention Type: DRUG

Administered at 2.5 g/m\^2.

Filgrastim

Intervention Type: BIOLOGICAL

Administered post cyclophosphamide daily until leukapheresis.

Leukapheresis

Intervention Type: PROCEDURE

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

Melphalan

Intervention Type: DRUG

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

Autologous stem cell transplant

Intervention Type: BIOLOGICAL

Infused on Day 0.

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.

Group Type: EXPERIMENTAL

Activated marrow infiltrating lymphocytes

Intervention Type: BIOLOGICAL

Administered on Days 3 and 4.

Allogeneic Myeloma Vaccine

Intervention Type: BIOLOGICAL

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

Cyclophosphamide

Intervention Type: DRUG

Administered at 2.5 g/m\^2.

Filgrastim

Intervention Type: BIOLOGICAL

Administered post cyclophosphamide daily until leukapheresis.

Leukapheresis

Intervention Type: PROCEDURE

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

Melphalan

Intervention Type: DRUG

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

Autologous stem cell transplant

Intervention Type: BIOLOGICAL

Infused on Day 0.

Interventions

Activated marrow infiltrating lymphocytes

Administered on Days 3 and 4.

Intervention Type: BIOLOGICAL

Allogeneic Myeloma Vaccine

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

Intervention Type: BIOLOGICAL

Cyclophosphamide

Administered at 2.5 g/m\^2.

Intervention Type: DRUG

Filgrastim

Administered post cyclophosphamide daily until leukapheresis.

Intervention Type: BIOLOGICAL

Leukapheresis

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

Intervention Type: PROCEDURE

Melphalan

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

Intervention Type: DRUG

Autologous stem cell transplant

Infused on Day 0.

Intervention Type: BIOLOGICAL

Other Intervention Names

MILs; aMILs; Cytoxan; G-CSF; Apheresis; Alkeran; ASCT

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ivan Borrello, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NA_00029491

Identifier Type: OTHER

Identifier Source: secondary_id

J0997

Identifier Type: -

Identifier Source: org_study_id