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Vaccine Therapy in Treating Patients With Multiple Myeloma Who Have Undergone Stem Cell Transplantation

Primary Purpose

Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
autologous immunoglobulin idiotype-KLH conjugate vaccine
sargramostim
aldesleukin
laboratory biomarker analysis
Sponsored by
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Multiple Myeloma

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: ELIGIBILITY FOR VACCINE PREPARATION: Patients must have a diagnosis of multiple myeloma and be eligible for a Fred Hutchinson Cancer Research Center (FHCRC) treatment protocol using high dose therapy with syngeneic, allogeneic or autologous marrow or stem cell transplantation Pretransplant sera available with immunoglobulin A (IgA), immunoglobulin D (IgD), immunoglobulin E (IgE), immunoglobulin G (IgG), or immunoglobulin M (IgM) monoclonal paraprotein with a level of 1.5 grams/dl or greater identifiable on serum protein electrophoresis; eligibility for patients with pretransplant paraprotein levels of less than 1.5 gm/dl will be evaluated on an individual basis to determine whether purification of idiotype is feasible ELIGIBILITY FOR POST-TRANSPLANT IDIOTYPE VACCINATION: Successful isolation and production of an autologous idiotype vaccine from pre-BMT sera Greater than 60 days post BMT Achievement of a partial remission or greater (more than 75% reduction in serum paraprotein) for patients transplanted in relapse Stable absolute neutrophil count (ANC) > 1000 Platelet count > 50,000 not requiring transfusions or growth factors Red blood cell (RBC) supportable to hematocrit (Hct) > 25 with less than 2 units of packed red blood cell (PRBC)/week Treatment with a stable dose of Interferon is allowed Karnofsky status > 60 percent Immunosuppression: Off all corticosteroids Either off all immunosuppressive medications or on a stable/tapering dose of cyclosporin or FK506 only Exclusion Criteria: Graft-vs-host disease requiring treatment with corticosteroids Serum creatinine > 3.0 Uncontrolled infection Disease progression Presence of medical complication that in the opinion of the investigators would result in inability to tolerate the vaccination protocol Patients with a history of serious adverse reactions to GM-CSF Patients with a history of serious adverse reactions to IL-2 will not receive concurrent IL-2 administration but may receive the Id-KLH vaccine with GM-CSF

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (vaccine therapy)

Arm Description

Patients receive autologous immunoglobulin idiotype-KLH conjugate vaccine combined with sargramostim SC in weeks 0, 2, 6, and 10 and sargramostim SC QD for three days following each vaccine injection. Some patients also receive aldesleukin SC daily from weeks 2-14.

Outcomes

Primary Outcome Measures

Toxicities graded using the National Cancer Institute (NCI) Common Toxicity Criteria
Descriptive statistics will be used to summarize changes from baseline in clinical laboratory parameters for each cohort.
Immune response
Descriptive statistics will be used to summarize changes from baseline in clinical laboratory parameters for each cohort.

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
May 2, 2019
Sponsor
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00002787
Brief Title
Vaccine Therapy in Treating Patients With Multiple Myeloma Who Have Undergone Stem Cell Transplantation
Official Title
Phase I Trial of Post Transplant Immunization With Autologous Myeloma Idiotype-KLH/GM-CSF In Myeloma Patients Following Autologous or Allogeneic Marrow or Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
March 1996 (undefined)
Primary Completion Date
December 2002 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
The purpose of this trial is to test the safety and immune response to four immunizations with this vaccine made from a protein produced by the patient's tumor. There is no guarantee or promise that this procedure will be successful
Detailed Description
PRIMARY OBJECTIVES: I. To determine the safety of multiple subcutaneous vaccinations with myeloma Id-KLH (idiotype-keyhole limpet hemocyanin) with GM-CSF (sargramostim) in post allogeneic transplant myeloma patients, or with GM-CSF +/- interleukin (IL)-2 (aldesleukin) in post autologous transplant myeloma patients. II. To evaluate patients pre and post bone marrow transplantation (BMT) for evidence of endogenous idiotype specific immune response. III. To characterize the time course, specificity and persistence of antibody and T cell immune response to myeloma idiotype and to KLH induced by myeloma Ig (Id) immunization. IV. To clone, expand and characterize T cells specific for the tumor idiotype. V. Monitor myeloma involvement in bone marrow and serum paraprotein level following vaccination. VI. Use stored patient samples to clone, expand, and characterize T cells specific for myeloma antigens other than idiotype and identify the antigens they recognize so that they can be used in future studies. OUTLINE: Patients receive autologous immunoglobulin idiotype-KLH conjugate vaccine combined with sargramostim subcutaneously (SC) in weeks 0, 2, 6, and 10 and sargramostim SC once daily (QD) for three days following each vaccine injection. Some patients also receive aldesleukin SC daily from weeks 2-14. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 1 year.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (vaccine therapy)
Arm Type
Experimental
Arm Description
Patients receive autologous immunoglobulin idiotype-KLH conjugate vaccine combined with sargramostim SC in weeks 0, 2, 6, and 10 and sargramostim SC QD for three days following each vaccine injection. Some patients also receive aldesleukin SC daily from weeks 2-14.
Intervention Type
Biological
Intervention Name(s)
autologous immunoglobulin idiotype-KLH conjugate vaccine
Other Intervention Name(s)
autologous immunoglobulin idiotype-keyhole limpet hemocyanin conjugate vaccine, GTOP-99, Id-KLH, Id-KLH conjugate vaccine, recombinant Id-KLH
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
sargramostim
Other Intervention Name(s)
GM-CSF, Leukine, Prokine
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
aldesleukin
Other Intervention Name(s)
IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2
Intervention Description
Given SC
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Toxicities graded using the National Cancer Institute (NCI) Common Toxicity Criteria
Description
Descriptive statistics will be used to summarize changes from baseline in clinical laboratory parameters for each cohort.
Time Frame
Up to 2 years
Title
Immune response
Description
Descriptive statistics will be used to summarize changes from baseline in clinical laboratory parameters for each cohort.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ELIGIBILITY FOR VACCINE PREPARATION: Patients must have a diagnosis of multiple myeloma and be eligible for a Fred Hutchinson Cancer Research Center (FHCRC) treatment protocol using high dose therapy with syngeneic, allogeneic or autologous marrow or stem cell transplantation Pretransplant sera available with immunoglobulin A (IgA), immunoglobulin D (IgD), immunoglobulin E (IgE), immunoglobulin G (IgG), or immunoglobulin M (IgM) monoclonal paraprotein with a level of 1.5 grams/dl or greater identifiable on serum protein electrophoresis; eligibility for patients with pretransplant paraprotein levels of less than 1.5 gm/dl will be evaluated on an individual basis to determine whether purification of idiotype is feasible ELIGIBILITY FOR POST-TRANSPLANT IDIOTYPE VACCINATION: Successful isolation and production of an autologous idiotype vaccine from pre-BMT sera Greater than 60 days post BMT Achievement of a partial remission or greater (more than 75% reduction in serum paraprotein) for patients transplanted in relapse Stable absolute neutrophil count (ANC) > 1000 Platelet count > 50,000 not requiring transfusions or growth factors Red blood cell (RBC) supportable to hematocrit (Hct) > 25 with less than 2 units of packed red blood cell (PRBC)/week Treatment with a stable dose of Interferon is allowed Karnofsky status > 60 percent Immunosuppression: Off all corticosteroids Either off all immunosuppressive medications or on a stable/tapering dose of cyclosporin or FK506 only Exclusion Criteria: Graft-vs-host disease requiring treatment with corticosteroids Serum creatinine > 3.0 Uncontrolled infection Disease progression Presence of medical complication that in the opinion of the investigators would result in inability to tolerate the vaccination protocol Patients with a history of serious adverse reactions to GM-CSF Patients with a history of serious adverse reactions to IL-2 will not receive concurrent IL-2 administration but may receive the Id-KLH vaccine with GM-CSF
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Maloney
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

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Vaccine Therapy in Treating Patients With Multiple Myeloma Who Have Undergone Stem Cell Transplantation

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