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Chemotherapy and Peripheral Stem Cell Transplantation Followed By Immunotherapy in Treating Patients With Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00046852
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : November 4, 2019
University of Maryland Greenebaum Cancer Center
Information provided by:
University of Maryland, Baltimore

Tracking Information
First Submitted Date  ICMJE October 3, 2002
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date November 4, 2019
Study Start Date  ICMJE December 2001
Actual Primary Completion Date November 2004   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00046852 on Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Chemotherapy and Peripheral Stem Cell Transplantation Followed By Immunotherapy in Treating Patients With Multiple Myeloma
Official Title  ICMJE High-Dose Therapy and Autologous Blood Stem Cell Transplantation (ASCT) Followed by Post-Transplant Immunotherapy With Costimulated Autologous T-Cells in Conjunction With Pneumococcal Conjugate Vaccine Immunization for Patients With Multiple Myeloma
Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous peripheral stem cell transplantation and immunotherapy may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing.

PURPOSE: Randomized phase I/II trial to study the effectiveness of combining chemotherapy with peripheral stem cell transplantation followed by immunotherapy in treating patients who have multiple myeloma.

Detailed Description


  • Determine the feasibility of expanding ex vivo autologous T cells and infusing these cells after high-dose chemotherapy and autologous peripheral blood stem cell rescue in patients with multiple myeloma.
  • Determine the response rate and progression-free survival of patients who receive anti-CD3/anti-CD28 expanded autologous T cells on either day 14 or day 100 post-transplantation.
  • Compare response and survival rates of these patients to historical controls.
  • Determine the optimal schedule for pneumococcal conjugate vaccine (PCV) to induce an anti-pneumococcal immune response post-transplantation in these patients.
  • Determine whether "vaccine education" of antigen-presenting cells (APCs) in the stem cell graft results in an earlier and/or enhanced immune response than with a graft containing "non-educated" APCs in these patients.
  • Determine whether an infusion of T cells presensitized to the PCV and expanded ex vivo contributes to the anti-pneumococcal immune response in these patients.

OUTLINE: This is a randomized, multicenter study.

Patients receive cyclophosphamide IV over 12 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 2. Patients undergo leukapheresis to collect mononuclear cells for autologous T cells (ATCs) and peripheral blood stem cells (PBSCs). ATCs are generated by ex vivo expansion for 8-14 days and selection for CD3+/CD28+ cells.

Patients then receive high-dose therapy comprising carmustine IV over 2 hours on day -2 and melphalan IV over 20 minutes on day -1 or melphalan IV alone on days -2 and -1 (or day -1 only). Autologous PBSCs are reinfused on day 0. Patients also receive G-CSF SC beginning on day 1 and continuing until blood counts recover.

Patients who choose to receive pneumococcal conjugate vaccine (PCV) are randomized to 1 of 4 treatment arms.

  • Arm I: Patients receive PCV intramuscularly prior to transplantation (10-14 days before lymphocyte collection) and post-transplantation (1 and 3 months) plus costimulated ATCs IV over 20-60 minutes around day 12-14 post-transplantation.
  • Arm II: Patients receive PCV as in arm I but receive ATCs around day 100 post-transplantation.
  • Arm III: Patients receive PCV post-transplantation only (at 1 and 3 months) plus ATCs as in arm I.
  • Arm IV: Patients receive PCV as in arm III and ATCs as in arm II. Patients who choose not to receive the PCV receive ATCs on about day 12-14 after PBSC transplantation.

All patients are offered standard pneumococcal polysaccharide vaccine at 12 months.

Patients are followed twice weekly until day 60, weekly for 4 months, monthly for 6 months, and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 16-46 patients will be accrued for this study within 14 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Primary Purpose: Treatment
Condition  ICMJE
  • Infection
  • Multiple Myeloma and Plasma Cell Neoplasm
Intervention  ICMJE
  • Biological: filgrastim
  • Biological: pneumococcal polyvalent vaccine
  • Biological: therapeutic autologous lymphocytes
  • Biological: therapeutic tumor infiltrating lymphocytes
  • Drug: carmustine
  • Drug: cyclophosphamide
  • Drug: melphalan
  • Procedure: bone marrow ablation with stem cell support
  • Procedure: peripheral blood stem cell transplantation
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE Not Provided
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE February 2008
Actual Primary Completion Date November 2004   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE


  • Diagnosis of multiple myeloma requiring systemic treatment
  • No obvious myelodysplastic changes in the marrow



  • 18 to 80

Performance status

  • ECOG 0-2 (ECOG 3-4 allowed if based solely on bone pain)

Life expectancy

  • Not specified


  • Not specified


  • No chronic active hepatitis
  • No liver cirrhosis


  • Creatinine no greater than 3.0 mg/dL
  • No dialysis


  • LVEF at least 45% unless no evidence of untreated clinically significant functional impairment


  • FEV_1 and FVC at least 50% of predicted
  • Total lung capacity at least 50% of predicted
  • DLCO at least 50% of predicted
  • Mild to moderate pulmonary impairment (lower DLCO) allowed but patients would not receive study carmustine
  • Patients unable to complete pulmonary function test due to bone pain or fracture must have high-resolution CT scan of the chest and arterial partial pressure of oxygen greater than 70


  • No active infections requiring IV antibiotics
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception


Biologic therapy

  • Not specified


  • Not specified

Endocrine therapy

  • Prior pulse dexamethasone (1-2 courses) allowed
  • Concurrent pulse dexamethasone allowed during mobilization therapy


  • Not specified


  • Not specified
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00046852
Other Study ID Numbers  ICMJE CDR0000256870
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE University of Maryland, Baltimore
Collaborators  ICMJE University of Maryland Greenebaum Cancer Center
Investigators  ICMJE
Study Chair: Aaron P. Rapoport, MD University of Maryland Greenebaum Cancer Center
PRS Account University of Maryland, Baltimore
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP