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Chemioterapia skojarzona, przeszczep obwodowych komórek macierzystych, terapia biologiczna, pamidronian i talidomid w leczeniu szpiczaka mnogiego

15 października 2026 zaktualizowane przez: City of Hope Medical Center

Sekwencyjne podawanie dużych dawek melfalanu i busulfanu/cyklofosfamidu, a następnie podanie komórek progenitorowych krwi obwodowej, interferonu/talidomidu i pamidronianu u pacjentów ze szpiczakiem mnogim

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more cancer cells. Biological therapies, such as interferon alfa, use different ways to stimulate the immune system and stop cancer cells from growing. Thalidomide may stop the growth of cancer cells by stopping blood flow to the tumor. Pamidronate may help to reduce the side effects of treatment for multiple myeloma.

PURPOSE: This phase II trial is studying combination chemotherapy, peripheral stem cell transplantation, biological therapy, pamidronate, and thalidomide to see how well they work in treating patients with stage I, stage II, or stage III multiple myeloma.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

OBJECTIVES:

  • Determine the feasibility and toxic effects of high-dose melphalan, busulfan, and cyclophosphamide followed by autologous peripheral blood stem cell rescue, interferon alfa, and pamidronate in patients with responsive or stable, low-bulk multiple myeloma.
  • Determine the response rate and progression-free and overall survival of patients treated with this regimen.
  • Determine the feasibility of adding thalidomide to interferon alfa and pamidronate in patients who are not in complete remission (CR) 6 months after the second course of high-dose chemotherapy.
  • Determine whether administration of thalidomide can increase the CR rate in patients who are not in CR 6 months after the second course of high-dose chemotherapy and determine its effect on progression-free and overall survival of these patients.
  • Determine the pharmacokinetics of busulfan and cyclophosphamide and correlate the pharmacokinetics with the toxic effects of these drugs and outcome in these patients.
  • Determine the effect of thalidomide on microvascular density of bone marrow and correlate these possible effects with outcome in these patients.
  • Determine the cytogenetics, gene rearrangement, and fluorescence in situ hybridization in baseline and post treatment bone marrow and blood specimens and correlate the presence/persistence of these features with treatment outcome in these patients.

OUTLINE: Patients receive cyclophosphamide IV over 2 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) or IV twice a day beginning on day 2 and continuing until peripheral blood stem cells (PBSCs) are collected. PBSCs are collected beginning on day 10.

Patients receive high-dose melphalan IV on day -1. PBSCs are reinfused on day 0. G-CSF is administered IV or SC daily beginning on day 1 and continuing until blood counts recover. Between 8 and 14 weeks later, patients receive high-dose busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. PBSCs are reinfused on day 0 and G-CSF is administered IV or SC daily until blood counts recover.

Patients with responding or stable disease after chemotherapy receive maintenance therapy with interferon alfa beginning 14-20 weeks after day 0 of the second course of chemotherapy. Interferon alfa is administered SC 3 times a week for 3 years. Patients also receive pamidronate IV every 4 weeks until disease progression. Patients who are not in complete remission (CR) 6 months after completing the second course of chemotherapy receive oral thalidomide daily for a maximum of 1 year or for 3 months after achieving CR.

Patients are followed monthly for 1 year, every 3 months for 1 year, and then periodically thereafter.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study within approximately 2.5 years.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

77

Faza

  • Faza 2

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Stany Zjednoczone
    • Arizona
      • Phoenix, Arizona, Stany Zjednoczone, 85006
        • Banner Good Samaritan Medical Center
    • California
      • Duarte, California, Stany Zjednoczone, 91010-3000
        • City of Hope Comprehensive Cancer Center

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

1 sekunda do 65 lat (Dziecko, Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

DISEASE CHARACTERISTICS:

  • Histologically proven stage I-III multiple myeloma

    • Less than 18 months since diagnosis

    • Smoldering myeloma allowed if there is evidence of progressive disease requiring therapy

      • At least 25% increase in M protein levels or Bence Jones excretion
      • Hemoglobin no greater than 10.5 g/dL
      • Hypercalcemia
      • Frequent infections
      • Rise in serum creatinine above normal on 2 separate occasions

    • Nonquantifiable monoclonal proteins allowed if other criteria for multiple myeloma or smoldering myeloma are met

  • Response/status after induction therapy:

    • Responding or stable disease AND no greater than 40% myelomatous involvement of bone marrow

  • No Waldenstrom's macroglobulinemia

PATIENT CHARACTERISTICS:

Age:

  • 65 and under

Performance status:

  • Karnofsky 80-100%

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics
  • Absolute neutrophil count greater than 1,500/mm^3
  • Platelet count greater than 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 1.5 mg/dL
  • Serum glutamic axaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) less than 2.5 times upper limit of normal
  • Hepatitis B antigen or hepatitis C ribonucleaic acid (RNA) negative

Renal:

  • See Disease Characteristics
  • Creatinine no greater than 1.4 mg/dL
  • Creatinine clearance greater than 65 mL/min

Cardiovascular:

  • Cardiac ejection fraction at least 50% by multigated acquisition scan (MUGA) or echocardiogram

Pulmonary:

  • Forced-expiratory volume in one second (FEV_1) greater than 60% of normal
  • Diffusing capacity for carbon monoxide (DLCO) greater than 50% of predicted lower limit

Other:

  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Human immunodeficiency virus (HIV) negative
  • No other medical or psychosocial problems that would increase patient risk
  • No other malignancy within past 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix
  • No known hypersensitivity to filgrastim (G-CSF) or Escherechi coli-derived proteins

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • See Disease Characteristics
  • No more than 3 prior chemotherapy regimens
  • At least 4 weeks since prior chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • At least 4 weeks since prior radiotherapy

Surgery:

  • Not specified

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Nie dotyczy
  • Model interwencyjny: Zadanie dla jednej grupy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: HD chemotherapy followed by PBPC Rescue

Patients receive high-dose (HD) melphalan intra-venously (IV) on day -1. Peripheral blood progenitor cells (PBPCs) are reinfused on day 0. Filgrastim (G-CSF) is administered IV or SC daily beginning on day 1 and continuing until blood counts recover. Between 8 and 14 weeks later, patients receive IV high-dose busulfan every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. PBPCs are reinfused on day 0 and G-CSF is administered IV or subcutaneously (SC) daily until blood counts recover.
Biologiczny: rekombinowany interferon alfa
Inne nazwy:
  • IFN alfa-2B
  • Intron A
Lek: cyklofosfamid
Inne nazwy:
  • Cytoksan
  • cytofosfan
Lek: busulfan
Inne nazwy:
  • Busulfex
  • Myleran
Procedura: przeszczep komórek macierzystych krwi obwodowej
Inne nazwy:
  • przeszczep komórek progenitorowych krwi obwodowej
Biologiczny: filgrastym
Inne nazwy:
  • Neupogen
  • czynnik stymulujący tworzenie kolonii granulocytów (G-CSF)
Lek: melfalan
Inne nazwy:
  • Alkeran
  • Evomela
Lek: talidomid
Inne nazwy:
  • Talidomid
  • Immunoprina
Lek: disodu pamidronianu
Inne nazwy:
  • kwas pamidronowy

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Best Response Prior to Tandem Autologous Stem Cell Transplant
Ramy czasowe: From enrollment in the study until day -8: before dilantin given pre-first high-dose chemo preceeding first cycle of tandem autologous cell transplant

Response gradations are specified in the "Blade criteria", Br J Haematol 1998; 102: 1115-1123. Serum myeloma protein is measured 2x at least six weeks apart, and urine M-component is measured 2x at least 3 weeks apart. Complete response (CR): less than 3% plasma cells in bone marrow or blood. Very good partial response (VGPR): Greater than 90% decrease in myeloma protein, and urine M-component less than 0.1 gm/day. Partial response (PR) Greater than 50% decrease in myeloma protein; urine M-component less than 0.2 gm/day. Lytic skeletal lesions must not increase, and serum calcium level must remain normal. Stable disease (SD): 25-49% decrease in protein and 25% decrease in urine M-component. Progressive disease (PD): Greater than 25% increase in myeloma protein, or hypercalcemia. Relapse: 1) increase greater than 100% of myeloma protein; 2) More than 25% increase of myeloma protein; 3) reappearance of the myeloma peaks; 4) increase in lytic bone lesions on radiographs.
From enrollment in the study until day -8: before dilantin given pre-first high-dose chemo preceeding first cycle of tandem autologous cell transplant
Response After Tandem Autologous Stem Cell Transplant
Ramy czasowe: After second cycle of tandem autologous stem cell transplant: Day 0 of second transplant to 12 weeks post-cycle 2 cell infusion of the tandem transplant.

Response gradations are specified in the "Blade criteria", Br J Haematol 1998; 102: 1115-1123. Serum myeloma protein is measured 2x at least six weeks apart, and urine M-component is measured 2x at least 3 weeks apart. Complete response (CR): less than 3% plasma cells in bone marrow or blood. Very good partial response (VGPR): Greater than 90% decrease in myeloma protein, and urine M-component less than 0.1 gm/day. Partial response (PR) Greater than 50% decrease in myeloma protein; urine M-component less than 0.2 gm/day. Lytic skeletal lesions must not increase, and serum calcium level must remain normal. Stable disease (SD): 25-49% decrease in protein and 25% decrease in urine M-component. Progressive disease (PD): Greater than 25% increase in myeloma protein, or hypercalcemia. Relapse: 1) increase greater than 100% of myeloma protein; 2) More than 25% increase of myeloma protein; 3) reappearance of the myeloma peaks; 4) increase in lytic bone lesions on radiographs.
After second cycle of tandem autologous stem cell transplant: Day 0 of second transplant to 12 weeks post-cycle 2 cell infusion of the tandem transplant.
Three-year Overall Survival
Ramy czasowe: Estimate reported at three years after day 0 of the first cycle of infusion of cells of the tandem transplant.

Kaplan-Meier estimate at three years post-first transplant of survival. Outcome is death or alive at follow-up (censored). 95 percent confidence interval of the point estimate is calculated using Greenwood's variance.
Estimate reported at three years after day 0 of the first cycle of infusion of cells of the tandem transplant.
Progression-free Survival
Ramy czasowe: Estimate reported at three years after day 0 of the first cycle of infusion of cells of the tandem transplant.

Kaplan-Meier estimate at three years post-first transplant of survival. Event of interest is the first of Death or Progression. Censoring is Alive in Continuous Complete Remission at date of last follow-up.

95 percent confidence interval of the point estimate is calculated using Greenwood's variance.
Estimate reported at three years after day 0 of the first cycle of infusion of cells of the tandem transplant.
Best Response at 6 Months Post Tandem Autologous Stem Cell Transplant
Ramy czasowe: Six months after day 0 of the first cycle of the tandem autologous stem cell transplant. This will be used to determine administration of thalidomide.

Response gradations are specified in the "Blade criteria", Br J Haematol 1998; 102: 1115-1123. Serum myeloma protein is measured 2x at least six weeks apart, and urine M-component is measured 2x at least 3 weeks apart. Complete response (CR): less than 3% plasma cells in bone marrow or blood. Very good partial response (VGPR): Greater than 90% decrease in myeloma protein, and urine M-component less than 0.1 gm/day. Partial response (PR) Greater than 50% decrease in myeloma protein; urine M-component less than 0.2 gm/day. Lytic skeletal lesions must not increase, and serum calcium level must remain normal. Stable disease (SD): 25-49% decrease in protein and 25% decrease in urine M-component. Progressive disease (PD): Greater than 25% increase in myeloma protein, or hypercalcemia. Relapse: 1) increase greater than 100% of myeloma protein; 2) More than 25% increase of myeloma protein; 3) reappearance of the myeloma peaks; 4) increase in lytic bone lesions on radiographs.
Six months after day 0 of the first cycle of the tandem autologous stem cell transplant. This will be used to determine administration of thalidomide.
Best Response After Tandem Autologous Stem Cell Transplant and Maintenance
Ramy czasowe: Response after six months after day 0 of the first cycle of the tandem transplant, after administration of maintenance thalidomide if necessary, until three years post-day 0 of the first cycle of the tandem transplant.

Response gradations are specified in the "Blade criteria", Br J Haematol 1998; 102: 1115-1123. Serum myeloma protein is measured 2x at least six weeks apart, and urine M-component is measured 2x at least 3 weeks apart. Complete response (CR): less than 3% plasma cells in bone marrow or blood. Very good partial response (VGPR): Greater than 90% decrease in myeloma protein, and urine M-component less than 0.1 gm/day. Partial response (PR) Greater than 50% decrease in myeloma protein; urine M-component less than 0.2 gm/day. Lytic skeletal lesions must not increase, and serum calcium level must remain normal. Stable disease (SD): 25-49% decrease in protein and 25% decrease in urine M-component. Progressive disease (PD): Greater than 25% increase in myeloma protein, or hypercalcemia. Relapse: 1) increase greater than 100% of myeloma protein; 2) More than 25% increase of myeloma protein; 3) reappearance of the myeloma peaks; 4) increase in lytic bone lesions on radiographs.
Response after six months after day 0 of the first cycle of the tandem transplant, after administration of maintenance thalidomide if necessary, until three years post-day 0 of the first cycle of the tandem transplant.

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

City of Hope Medical Center

Współpracownicy

National Cancer Institute (NCI)

Śledczy

  • Główny śledczy: George Somlo, MD, City of Hope Medical Center

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

  • Long-term Progression-free (PFS) and Overall Survival (OS) with Tandem Autologous Transplant (TASCT) After High-dose Induction With Melphalan (MEL) and Busulfan/cyclophosphamide (BU/CY), or a Novel Regimen of MEL and Total Marrow Irradiation (TMI), Followed by Maintenance With Interferon A-2 (IF) and/or Thalidomide (THAL). Haematologica 96(s1), 2011, s103. G. Somlo, J. Palmer, A. Dagis, M. O'Donnell, D. Snyder, F. Sahebi, N. Kogut, A. Brown, R. Spielberger, P.Parker, C. Karanes, L. Popplewell, A. Stein, A. Krishnan, J. Alvarnas, J. Wong, S. Forman.

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

8 lipca 1999

Zakończenie podstawowe (Rzeczywisty)

9 stycznia 2018

Ukończenie studiów (Rzeczywisty)

9 stycznia 2018

Daty rejestracji na studia

Pierwszy przesłany

10 grudnia 1999

Pierwszy przesłany, który spełnia kryteria kontroli jakości

26 stycznia 2003

Pierwszy wysłany (Szacowany)

27 stycznia 2003

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

3 listopada 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

15 października 2026

Ostatnia weryfikacja

1 października 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • 99021
  • P30CA033572 (Grant/umowa NIH USA)
  • CHNMC-IRB-99021 (Inny identyfikator: City of Hope Institutional Review Board)
  • NCI-G99-1583 (Inny identyfikator: National Cancer Institute)
  • CDR0000067301 (Identyfikator rejestru: NCI PDQ)

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

NIE

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