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High-Dose Chemotherapy and Stem Cell Transplant in Treating Patients With Newly Diagnosed Stage I, Stage II, or Stage III Multiple Myeloma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2007 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00526734
First received: September 5, 2007
Last updated: August 9, 2013
Last verified: September 2007
  Purpose

RATIONALE: Drugs used in chemotherapy, such as melphalan, use different ways to stop cancer cells from dividing so they stop growing or die. 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 colony-stimulating factors, such as G-CSF or pegfilgrastim, helps stem cells move from the bone marrow to the blood so they can be collected. It is not yet known which regimen is more effective in treating multiple myeloma.

PURPOSE: This randomized phase II trial is studying how well high-dose chemotherapy followed by stem cell transplant works in treating patients with newly diagnosed stage I, stage II, or stage III multiple myeloma.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Biological: filgrastim
Biological: pegfilgrastim
Drug: melphalan
Procedure: autologous hematopoietic stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised, International, Open-label, Phase II Study of Peripheral Blood Progenitor Cell (PBPC) Mobilization and Engraftment With Pegfilgrastim or Filgrastim for Autologous Transplantation in Patients With Multiple Myeloma (MM)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of patients with engraftment after induction chemotherapy [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number and proportion of patients from whom ≥ 2 x 10e6 CD34-positive cells/kg are harvested [ Designated as safety issue: No ]
  • Number and proportion of patients from whom ≥ 4 x 10e6 CD34-positive cells/kg are harvested [ Designated as safety issue: No ]
  • CD34-positive cells/kg yield in each leukapheresis [ Designated as safety issue: No ]
  • Number of leukaphereses to collect ≥ 2 x 10e6 CD34-positive cells/kg [ Designated as safety issue: No ]
  • Number of leukaphereses to collect ≥ 4 x 10e6 CD34-positive cells/kg [ Designated as safety issue: No ]
  • Proportion of patients with platelet recovery ≥ 20 x 10e9/L in the absence of transfusion for at least 7 days [ Designated as safety issue: No ]
  • Proportion of patients with ANC recovery of ≥ 0.5 x 10e9/L [ Designated as safety issue: No ]
  • Time to neutrophil recovery, defined as the time to neutrophil engraftment (i.e., ANC ≥ 0.5 x 10e9/L for 3 consecutive days) [ Designated as safety issue: No ]
  • Time to ANC ≥ 1.0 x 10e9/L [ Designated as safety issue: No ]
  • Time to platelet recovery, defined as the time to platelets ≥ 20 x 10e9/L in the absence of platelet transfusion support for at least 7 days [ Designated as safety issue: No ]
  • Incidence and duration of hospitalization during mobilization phase and during post-transplantation phase [ Designated as safety issue: No ]
  • Incidence and severity of adverse events during and after the use of pegfilgrastim 12 mg or pegfilgrastim 18 mg and filgrastim [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: February 2006
Detailed Description:

OBJECTIVES:

Primary

  • Compare engraftment of peripheral blood progenitor cells (PBPCs) mobilized by 2 different fixed doses of pegfilgrastim versus a by-weight dose of filgrastim (G-CSF).

Secondary

  • Determine the ability of 2 different fixed doses of pegfilgrastim to mobilize PBPCs.
  • Determine the safety of pegfilgrastim during PBPC mobilization and collection.
  • Determine the effect of different induction chemotherapy regimens on autologous progenitor cell transplantation.

OUTLINE: This is a multicenter study. Patients are stratified by type of induction chemotherapy (Thal/Dex vs VAD vs Vel-Dex vs VTD) and by stage of disease according to International Prognostic Index criteria (stage I [i.e., beta-2 microglobulin < 3.5 and albumin > 35] vs stages II and III).

  • Induction therapy: Patients receive 3-4 courses of 1 of the following regimens:

    • VAD: Patients receive vincristine, doxorubicin hydrochloride, and dexamethasone.
    • Thal/Dex: Patients receive thalidomide and dexamethasone.
    • Vel-Dex: Patients receive bortezomib and dexamethasone.
    • VTD: Patients receive bortezomib, thalidomide, and dexamethasone. Patients achieving complete, partial, or minimal response after 3-4 courses of induction therapy proceed to peripheral blood progenitor cell (PBPC) mobilization 17 days after completion of induction therapy.
  • PBPC mobilization: Patients are randomized to 1 of 3 arms.

    • Arm I: Patients receive filgrastim subcutaneously (SC) once daily until the final leukapheresis.
    • Arm II: Patients receive a single dose of pegfilgrastim SC.
    • Arm III: Patients receive pegfilgrastim as in arm II at a higher dose.
  • Leukapheresis: Patients undergo up to 3 leukaphereses to obtain adequate numbers of CD34-positive filgrastim- or pegfilgrastim-mobilized PBPCs for engraftment. Patients achieving a sufficient number of collected PBSCs proceed to conditioning chemotherapy.
  • Conditioning chemotherapy: Patients receive high-dose melphalan* IV over 1-2 days. Patients then proceed to PBPC transplantation.

NOTE: *Patients ≥ 65 years old receive melphalan at a lower dose.

  • Autologous PBPC transplantation: Patients undergo infusion of PBPCs on day 0. Patients in all arms receive G-CSF support beginning on day 1 after PBPC transplantation and continuing until blood counts recover for 3 consecutive days.

After completion of study therapy, patients are followed for up to 100 days post-transplantation.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of symptomatic stage I or stage II-III multiple myeloma

    • Newly diagnosed disease
  • No amyloidosis

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • ECOG performance status 0-2
  • ANC ≥ 1.0 x 10^9/L (without colony-stimulating factors)
  • Platelet count ≥ 50 x 10^9/L (without transfusion support within the past 7 days)
  • Serum calcium < 14 mg/dL
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 times ULN
  • Creatinine clearance ≥ 50 mL/min
  • Fertile patients must use effective contraception
  • Negative pregnancy test
  • Willing and able to comply with protocol requirements

Exclusion criteria:

  • Myocardial infarction within the past 6 months
  • New York Heart Association class III or IV heart failure
  • Uncontrolled angina
  • Severe uncontrolled ventricular arrhythmia
  • Acute ischemia or active conduction system abnormalities as evidenced by ECG
  • Serious medical condition that could prolong hematological recovery or preclude completion of or tolerance to protocol therapy
  • Seropositive for HIV antibody
  • Known hepatitis B surface antigen positivity OR active hepatitis C infection
  • Active systemic infection requiring treatment
  • Pregnant or nursing
  • Poor psychiatric condition

PRIOR CONCURRENT THERAPY:

  • No plasmapheresis within the past 4 weeks
  • No major surgery within the past 4 weeks
  • No anticancer therapy within the past 5 years, except treatment for basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix
  • No other concurrent G-CSF growth factors
  • No concurrent enrollment in another investigational clinical trial
  • No concurrent investigational agent that would contraindicate the use of pegfilgrastim as either a mobilization agent or a hematological recovery agent
  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: NCT00526734

Locations
Belgium
Hopital Universitaire Erasme Recruiting
Brussels, Belgium, 1070
Contact: Walter Feremans, MD, PhD    32-2-555-3660    wfereman@ulb.ac.be   
Poland
Medical University of Gdansk Recruiting
Gdansk, Poland, 80-211
Contact: Andrzej W. Hellmann, MD, PhD    48- 58-349-2230      
Silesian Medical Academy Recruiting
Katowice, Poland, 40-029
Contact: Jerzy Holowiecki, MD, PhD    48-32-256-2858    holow@slam.katowice.pl   
Institute of Haematology and Blood Transfusion Recruiting
Warsaw, Poland, 00-957
Contact: Krzysztof Warzocha, MD, PhD    48-22-849-8507    warzocha@ihit.waw.pl   
Sponsors and Collaborators
Hopital Universitaire Erasme
Investigators
Study Chair: Walter Feremans, MD, PhD Hopital Universitaire Erasme
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00526734     History of Changes
Other Study ID Numbers: ERA-2006-001, CDR0000561733, ERA-NEUMOBIL, EUDRACT-2006-000891-34
Study First Received: September 5, 2007
Last Updated: August 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage I multiple myeloma
stage II multiple myeloma
stage III 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
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 19, 2014