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

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

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

Study Overview

• Status: Completed
• Conditions: Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Refractory Multiple Myeloma
• Intervention / Treatment: Other: laboratory biomarker analysis; Biological: aldesleukin; Biological: sargramostim; Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (vaccine therapy); 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.

Other: laboratory biomarker analysis; Correlative studies; Biological: aldesleukin; Given SC; Other Names: Proleukin; IL-2; recombinant human interleukin-2; recombinant interleukin-2; Biological: sargramostim; Given SC; Other Names: Leukine; Prokine; GM-CSF; Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine; Given SC; Other Names: autologous immunoglobulin idiotype-keyhole limpet hemocyanin conjugate vaccine; GTOP-99; Id-KLH; Id-KLH conjugate vaccine; recombinant Id-KLH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 2 years
Immune response	Descriptive statistics will be used to summarize changes from baseline in clinical laboratory parameters for each cohort.	Up to 2 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: March 1, 1996
• Primary Completion (Actual): December 1, 2002

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: May 20, 2004
• First Posted (Estimate): May 21, 2004

Study Record Updates

• Last Update Posted (Actual): May 6, 2019
• Last Update Submitted That Met QC Criteria: May 2, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Aldesleukin; Antibodies; Vaccines; Immunoglobulins; Immunoglobulins, Intravenous; Immunoglobulin Idiotypes; Sargramostim; Interleukin-2; Keyhole-limpet hemocyanin
• Other Study ID Numbers: 1104.00; NCI-2012-00669 (Registry Identifier: CTRP (Clinical Trial Reporting Program))