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.

Anti-tumor Immune Response

The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (RANKL/OPG Ratio)

The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Serum C Telopeptide Levels)

The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (bAlkaline Phosphatase Levels)

The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Osteocalcin Levels)

Effect of aMILs on Clonogenic Myeloma Precursors

Overall Study

Lenalidomide

Heptavalent Pneumococcal Conjugate Vaccine

Angiogenesis Inhibitors

Growth Inhibitors

Lenalidomide will be continued on the same dose as was being administered prior to the study. The allogeneic myeloma vaccine and Prevnar-13 vaccine will be given on four days over the course of the study.

Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle).

A total of 4 vaccines will be administered. The first three at monthly intervals and a booster at 6 months from the initial vaccine. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed.

Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.

Prevnar-13

Ivan Borrello, M.D.

This research is being done to find out if the investigators can improve outcomes for multiple myeloma patients by giving a myeloma vaccine to patients who are already on lenalidomide (Revlimid) and in a near complete remission.

This is a single institution, single arm, Phase II study examining the clinical efficacy of an allogeneic GM-CSF secreting myeloma vaccine in combination with lenalidomide. Fifteen (15) patients enrolled in the study must have two disease measurements (including the last one) consistent with a near complete remission (M-spike negative with persistence of immunofixation) per criteria for response in a 6 month period. Patients will continue on the dose of lenalidomide they were on prior to being enrolled but will need to discontinue steroids for at least 4 weeks. Patients will receive 4 vaccinations on day 14(+/-3 days) of cycles 1, 2, 3 and 6 from enrollment that will include both the myeloma vaccine as well as Prevnar.

Allogeneic GM-CSF Vaccine and Lenalidomide in Treating Myeloma Patients With Near Complete Remission

Administration of an Allogeneic Myeloma GM-CSF Vaccine in Conjunction With a Lenalidomide Containing Regimen in Myeloma Patients With Near Complete Remission

Number of participants who converted from near complete remission (nCR) to complete remission (CR) as measured by the International Myeloma Working Group Uniform Response Criteria. Near complete remission is defined as negative serum and urine electrophoresis, \< 5% plasma cells in the bone marrow, and positive serum and/or urine immunofixation. Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with \< 5% plasma cells.

Median time for conversion of response from near complete remission (nCR) to complete remission (CR) as measured by the International Myeloma Working Group Uniform Response Criteria. Near complete remission is defined as negative serum and urine electrophoresis, \< 5% plasma cells in the bone marrow, and positive serum and/or urine immunofixation. Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with \< 5% plasma cells.

as measured by immunofixation converting from positive to negative.

Measures of stem cell population and plasma cell population.

Number of participants who experienced grade 3-4 toxicity as per CTCAE 4.0.

Immunity is measured by the percentage of CD3+/CSFSE-low/IFN-gamma+ cells. A positive result for a given participant is defined as greater than two standard deviations above that participant's baseline. The data are presented as three groups because the responses were analyzed separately, but all participants were part of the single study arm as represented by the remainder of the record. GVAX-specific immune response and Prevnar-specific immune response was assessed in the same patient by using GVAX and Prevnar-specific co-markers.

Celgene Corporation

Adverse events were assessed every 28 days.

Lenalidomide: Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle).

Allogeneic Myeloma Vaccine: A total of 4 vaccines will be administered. The first three at monthly intervals and a booster at 6 months from the initial vaccine. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed.

Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.

Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide

Lenalidomide: Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle).

Allogeneic Myeloma Vaccine: A total of 4 vaccines will be administered. The first three at monthly intervals and a booster at 6 months from the initial vaccine. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed.

Prevnar-13: Prevnar-13 will be administered at 0.5ml dose by intramuscular injection at the same time as GVAX vaccine.

United States

Region of Enrollment

One participant withdrew consent prior to receiving the study intervention, leaving sixteen participants who received at least one day of intervention.

Out of the 16 baseline participants, one received only one dose of vaccine and then had progression of disease. He was replaced and not included in this analysis.

Response Conversion Rate

Time to Response

Data was not collected for this outcome measure due to technical difficulties in the assay.

Effect on Clonogenic Myeloma Precursors

Grade 3-4 Toxicity

Complete Response (CR) patients at Baseline

CR patients at Cycle 3 Day 14

CR patients at end of Study

Progressive Disease (PD) patients at Baseline

PD patients at Cycle 3 Day 14

PD patients at end of study

Lenalidomide: Dosage forms: 5, 10, 15 and 25 mg capsules. Patients will be continued on the same dose of lenalidomide as they were prior to being enrolled in the study. Doses of lenalidomide for investigation can vary from 5- 25 mg/day, orally on days 1 - 21 followed by 7 days rest (28 day cycle).

Pre-vaccine (Baseline)

Allogeneic Myeloma Vaccine: A total of 4 doses will be administered. The first three at monthly intervals and a booster at 6 months from the initial dose. Each vaccination will consist of five total intra-dermal injections, two each in the right and left anterior upper thighs, and one in the non-dominant upper arm (unless contraindicated). Each dose will be administered on an outpatient basis. The subject must be observed in the clinic for at least 30 minutes after vaccination is completed.

GVAX Vaccine

Prevnar Vaccine

Out of the 16 baseline participants, one received only one dose of vaccine and then had progression of disease. He was replaced and not included in this analysis. Only 8/15 participants experienced complete response (CR), therefore only 8 participants analyzed in the CR rows and 7 participants analyzed in the progressive disease (PD) rows.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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	NCT01045460	Multiple Myelom...	Activated marro... Allogeneic Myel... Cyclophosphamid... Filgrastim Leukapheresis Melphalan Autologous stem...	18 Years - 70 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Allogeneic GM-CSF Vaccine and Lenalidomide in Treating Myeloma Patients With Near Complete Remission	NCT01349569	Multiple Myelom...	Lenalidomide Allogeneic Myel... Prevnar-13	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Allogeneic GM-CSF Vaccine and Lenalidomide in Treating Myeloma Patients With Near Complete Remission	NCT01349569	Multiple Myelom...	Lenalidomide Allogeneic Myel... Prevnar-13	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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