NCT00499577

Brief Summary

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
56

participants targeted

Target at P50-P75 for phase_1

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2006

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

July 10, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 11, 2007

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2009

Completed
Last Updated

January 10, 2014

Status Verified

August 1, 2009

Enrollment Period

2.2 years

First QC Date

July 10, 2007

Last Update Submit

January 9, 2014

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

stage I multiple myelomastage II multiple myelomastage III multiple myelomarefractory multiple myeloma

Outcome Measures

Primary Outcomes (3)

  • Toxicity at 21 and 28 days post-transplant

  • T-cell responses against the hTERT vaccine as measured by tetramer assays at 100 days post-transplant

  • Paraprotein levels in the blood or urine and serum free light chain analyses at 60 days and at 6 months post-transplant

Secondary Outcomes (6)

  • Cytotoxic T-cell responses against autologous myeloma cell at day 100 post-transplant via chromium-51 release or flow-based assays

  • Maximum clinical response

  • 1 and 2-year event-free survival

  • Overall survival rates

  • CD4 and CD8 T-cell responses against cytomegalovirus (CMV) at days 60 and 100 post-transplantation by CFSE dye dilution assays

  • +1 more secondary outcomes

Study Arms (4)

Group 1 (HLA-A2 positive)

EXPERIMENTAL

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 peptideBiological: hTERT I540/R572Y/D988Y multipeptide vaccineBiological: pneumococcal polyvalent vaccineBiological: survivin Sur1M2 peptide vaccine

Group 2

EXPERIMENTAL

Patients receive pneumococcal conjugate vaccine intramuscularly and GM-CSF subcutaneously.

Biological: CMV pp65 peptide

Second group 1

EXPERIMENTAL

On days 14, 42, and 90 post-transplant, patients receive peptides and GM-CSF subcutaneously and pneumococcal conjugate vaccine intramuscularly.

Biological: CMV pp65 peptideBiological: hTERT I540/R572Y/D988Y multipeptide vaccineBiological: pneumococcal polyvalent vaccineBiological: survivin Sur1M2 peptide vaccine

Second group 2

EXPERIMENTAL

On day 14, 42, 90 post-transplant, patients receive pneumococcal conjugate vaccine intramuscularly and GM-CSF subcutaneously.

Biological: CMV pp65 peptide

Interventions

CMV pp65 peptideBIOLOGICAL

Given intramuscularly

Group 1 (HLA-A2 positive)Group 2Second group 1Second group 2
hTERT I540/R572Y/D988Y multipeptide vaccineBIOLOGICAL

Given subcutaneously

Group 1 (HLA-A2 positive)Second group 1
pneumococcal polyvalent vaccineBIOLOGICAL

Given intramuscularly

Group 1 (HLA-A2 positive)Second group 1
survivin Sur1M2 peptide vaccineBIOLOGICAL

Given subcutaneously

Group 1 (HLA-A2 positive)Second group 1

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)
  • 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:
  • Recovered from any toxicities related to prior therapy or at least returned to their baseline level of organ function
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

Related Publications (2)

  • Rapoport AP, Aqui NA, Stadtmauer EA, Vogl DT, Fang HB, Cai L, Janofsky S, Chew A, Storek J, Akpek G, Badros A, Yanovich S, Tan MT, Veloso E, Pasetti MF, Cross A, Philip S, Murphy H, Bhagat R, Zheng Z, Milliron T, Cotte J, Cannon A, Levine BL, Vonderheide RH, June CH. Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma. Blood. 2011 Jan 20;117(3):788-97. doi: 10.1182/blood-2010-08-299396. Epub 2010 Oct 28.

    PMID: 21030558RESULT

  • Stadtmauer EA, Vogl DT, Luning Prak E, Boyer J, Aqui NA, Rapoport AP, McDonald KR, Hou X, Murphy H, Bhagat R, Mangan PA, Chew A, Veloso EA, Levine BL, Vonderheide RH, Jawad AF, June CH, Sullivan KE. Transfer of influenza vaccine-primed costimulated autologous T cells after stem cell transplantation for multiple myeloma leads to reconstitution of influenza immunity: results of a randomized clinical trial. Blood. 2011 Jan 6;117(1):63-71. doi: 10.1182/blood-2010-07-296822. Epub 2010 Sep 23.

    PMID: 20864577RESULT

MeSH Terms

Conditions

Multiple MyelomaNeoplasms, Plasma Cell

Interventions

Pneumococcal Vaccines

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Streptococcal VaccinesBacterial VaccinesVaccinesBiological ProductsComplex Mixtures

Study Officials

  • Aaron P. Rapoport, MD

    University of Maryland Greenebaum Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Purpose
TREATMENT
Sponsor Type
OTHER

Study Record Dates

First Submitted

July 10, 2007

First Posted

July 11, 2007

Study Start

December 1, 2006

Primary Completion

February 1, 2009

Last Updated

January 10, 2014

Record last verified: 2009-08

Locations

US(2)