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Stem Cell Transplant, Chemotherapy, and Biological Therapy in Treating Patients With High-Risk or Refractory Multiple Myeloma

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00499577
First received: July 10, 2007
Last updated: January 9, 2014
Last verified: August 2009
  Purpose

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. A stem cell transplant using stem cells from the patient may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. Giving an infusion of the donor's T cells after the transplant may help destroy any remaining cancer cells.

PURPOSE: This phase I/II trial is studying the side effects of stem cell transplant given together with chemotherapy and biological therapy and to see how well it works in treating patients with high-risk or refractory multiple myeloma.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Biological: CMV pp65 peptide
Biological: hTERT I540/R572Y/D988Y multipeptide vaccine
Biological: pneumococcal polyvalent vaccine
Biological: survivin Sur1M2 peptide vaccine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I/II Combination Immunotherapy After ASCT for Advanced Myeloma to Study HTERT Vaccination Followed by Adoptive Transfer of Vaccine-Primed Autologous T Cells

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Toxicity at 21 and 28 days post-transplant [ Designated as safety issue: Yes ]
  • T-cell responses against the hTERT vaccine as measured by tetramer assays at 100 days post-transplant [ Designated as safety issue: No ]
  • Paraprotein levels in the blood or urine and serum free light chain analyses at 60 days and at 6 months post-transplant [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cytotoxic T-cell responses against autologous myeloma cell at day 100 post-transplant via chromium-51 release or flow-based assays [ Designated as safety issue: Yes ]
  • Maximum clinical response [ Designated as safety issue: No ]
  • 1 and 2-year event-free survival [ Designated as safety issue: No ]
  • Overall survival rates [ Designated as safety issue: No ]
  • CD4 and CD8 T-cell responses against cytomegalovirus (CMV) at days 60 and 100 post-transplantation by CFSE dye dilution assays [ Designated as safety issue: No ]
  • Composite binding antibody responses at days 60 and day 100 post-transplant by ELISA [ Designated as safety issue: No ]

Estimated Enrollment: 56
Study Start Date: December 2006
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1 (HLA-A2 positive)
Patients receive the following peptides emulsified in incomplete Freund's adjuvant VG: I) hTERT I540 peptide; ii) hTERT R572Y peptide; iii) hTERT D988Y peptide; iv) survivin Sur1M2 peptide ; and v) CMV control peptide N495 subcutaneously (SC). Patients also receive sargramostim (GM-CSF) SC and pneumococcal conjugate vaccine intramuscularly.
Biological: CMV pp65 peptide
Given intramuscularly
Biological: hTERT I540/R572Y/D988Y multipeptide vaccine
Given subcutaneously
Biological: pneumococcal polyvalent vaccine
Given intramuscularly
Biological: survivin Sur1M2 peptide vaccine
Given subcutaneously
Experimental: Group 2
Patients receive pneumococcal conjugate vaccine intramuscularly and GM-CSF subcutaneously.
Biological: CMV pp65 peptide
Given intramuscularly
Experimental: Second group 1
On days 14, 42, and 90 post-transplant, patients receive peptides and GM-CSF subcutaneously and pneumococcal conjugate vaccine intramuscularly.
Biological: CMV pp65 peptide
Given intramuscularly
Biological: hTERT I540/R572Y/D988Y multipeptide vaccine
Given subcutaneously
Biological: pneumococcal polyvalent vaccine
Given intramuscularly
Biological: survivin Sur1M2 peptide vaccine
Given subcutaneously
Experimental: Second group 2
On day 14, 42, 90 post-transplant, patients receive pneumococcal conjugate vaccine intramuscularly and GM-CSF subcutaneously.
Biological: CMV pp65 peptide
Given intramuscularly

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of myeloma meeting 1 of the following criteria:

    • Myeloma has relapsed, progressed, or failed to respond after at least one prior course of therapy (consisting of at least 2 treatment cycles or months of therapy)

      • Failure to respond would correspond to a reduction of less than or equal to 25% of the original, diagnostic serum or urine paraprotein measurement
    • Myeloma has responded partially to initial therapy but a complete response (immunofixation negative) has NOT developed after a minimum of 3 cycles or months of initial therapy
    • Myeloma has high-risk features as defined by the presence of one or more cytogenetic abnormalities known to confer a poor outcome even after standard autotransplants (e.g., complex karyotype [≥ 3 abnormalities], t(4;14), t(14;16), del (17) (p13.1), and/or chromosome 13 abnormalities)

      • May be enrolled even while in complete or near-complete remission
      • Extended disease-free survival after autotransplantation would be unexpected for these patients and therefore especially meaningful
  • Must have measurable disease

    • Measurable disease may include quantifiable or detectable levels of serum or urine paraprotein

      • For patients with minimally secretory disease or non-secretory myeloma on study entry, serum free λ or κ light chain levels may be measured and used for disease monitoring if abnormal
      • Patients who are in complete remission at the time of proposed study entry (serum and urine immunofixation consistently negative) are not eligible unless their disease meets the criteria for high-risk disease
  • No known history of myelodysplasia

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • ECOG performance status 0-2 (unless due solely to bone pain)
  • Creatinine ≤ 3.0 mg/dL and not on dialysis
  • WBC ≥ 3,000/mm³
  • Platelet count ≥ 100,000/mm³
  • AST ≤ 2 times upper limit of normal
  • Bilirubin ≤ 2.0 mg/dL (unless due to Gilbert's syndrome)
  • LVEF ≥ 45%

    • A lower LVEF is permissible if a formal cardiologic evaluation reveals no evidence for clinically significant functional impairment
  • FEV1, FVC, TLC, and DLCO ≥ 40% predicted

    • Patients who are unable to complete pulmonary function tests due to bone pain or fracture must have a high-resolution CT scan of the chest and must have acceptable arterial blood gases (room air PO_2 > 70 mmHg)
  • Women of child-bearing potential and their spouses or partners must be willing to use adequate contraception for the duration of the active treatment phase of the study

    • Contraceptive measures must be continued as long as the patient remains on maintenance thalidomide in accordance with the STEPS program

Exclusion criteria

  • Pregnant or nursing
  • HIV, HTLV-1/2 seropositivity
  • Known history of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy)
  • Active hepatitis B (as defined by positive hepatitis B surface antigen)

    • Positive hepatitis C virus (HCV) antibody is NOT an exclusion
  • History of severe autoimmune disease requiring steroids or other immunosuppressive treatments
  • Active immune-mediated diseases including:

    • Connective tissue diseases
    • Uveitis
    • Sarcoidosis
    • Inflammatory bowel disease
    • Multiple sclerosis
  • Evidence or history of other significant cardiac, hepatic, renal, ophthalmologic, psychiatric, or gastrointestinal disease that might increase the risks of participating in the study
  • Active bacterial, viral or fungal infections.

PRIOR CONCURRENT THERAPY:

Inclusion criteria

  • Recovered from any toxicities related to prior therapy or at least returned to their baseline level of organ function
  • Patients should be off of glucocorticoids for at least 2 weeks and/or thalidomide therapy for at least 1 week prior to enrollment
  • At least 2 weeks since prior steroid therapy or chemotherapy

Exclusion criteria

  • Prior autotransplant or allogeneic transplant
  • More than 4 distinct, prior courses of therapy for myeloma
  • Also see Disease Characteristics
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00499577

Locations
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
Sponsors and Collaborators
University of Maryland Greenebaum Cancer Center
Investigators
Principal Investigator: Aaron P. Rapoport, MD University of Maryland Greenebaum Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Carl H. June, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00499577     History of Changes
Other Study ID Numbers: CDR0000552988, MSGCC-0610-GCC, UPCC-0610-GCC
Study First Received: July 10, 2007
Last Updated: January 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases

ClinicalTrials.gov processed this record on November 19, 2014