Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Molgramostim

Sargramostim

Vaccines

Melphalan

Lenograstim

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

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.

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.

Activated marrow infiltrating lymphocytes

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

Allogeneic Myeloma Vaccine

Administered post cyclophosphamide daily until leukapheresis.

Filgrastim

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

Leukapheresis

Autologous stem cell transplant

Ivan Borrello, MD

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.

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

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

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.

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

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

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

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.

* 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

• Examine side population of CD19 enriched PBLs throughout study.

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.

ASCT + MILs

ASCT + MILs + Vaccine

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Stage 1

Stage 2

Stage 3

Stage unknown

* Stage 1: Beta-2 microglobulin \< 3.5 mg/L and serum albumin \>= 3.5 g/dL.
* Stage 2: Neither stage 1 nor stage 3.
* Stage 3: Beta-2 microglobulin \>= 5.5 mg/L.

Higher beta-2 microglobulin reflects greater tumor mass. Therefore, a higher stage reflects a worse prognosis.

International Staging System (ISS) stage

VGPR

Only participants who had ASCT were evaluated for response. Three participants on the ASCT + MILs arm and two participants on the ASCT + MILs + vaccine arm were removed from study prior to ASCT and were therefore not evaluable for this outcome.

Response Rates by Blade Criteria

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.

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

Cyclophosphamide: Administered at 2.5 g/m\^2.

Filgrastim: Administered post cyclophosphamide daily until leukapheresis.

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

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

Autologous stem cell transplant: Infused on Day 0.

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.

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.

Cyclophosphamide: Administered at 2.5 g/m\^2.

Filgrastim: Administered post cyclophosphamide daily until leukapheresis.

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

Melphalan: 100 mg/m\^2/day given on Days -2

Progression-free Survival

Overall Survival

Feasibility as Measured by Participant Withdrawal or Removal

Safety as Measured by Grade 3-5 Adverse Events

This measure was not assessed. Data was not collected.

Spots Global Cancer Trial Database for activated marrow infiltrating lymphocytes