Kombinovaná chemoterapie, transplantace periferních kmenových buněk, biologická léčba, pamidronát a thalidomid pro mnohočetný myelom
Sekvenční vysoké dávky melfalanu a busulfanu/cyklofosfamidu následované záchranou progenitorových buněk periferní krve, interferonem/thalidomidem a pamidronátem pro pacienty s mnohočetným myelomem
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.
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Detailní popis
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 studie
Typ studie
Zápis (Aktuální)
Zápis
Fáze
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
-
-
Arizona
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Phoenix, Arizona, Spojené státy, 85006
- Banner Good Samaritan Medical Center
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-
California
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Duarte, California, Spojené státy, 91010-3000
- City of Hope Comprehensive Cancer Center
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-
Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
DISEASE CHARACTERISTICS:
-
Histologically proven stage I-III multiple myeloma
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Less than 18 months since diagnosis
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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
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Nonquantifiable monoclonal proteins allowed if other criteria for multiple myeloma or smoldering myeloma are met
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Response/status after induction therapy:
- Responding or stable disease AND no greater than 40% myelomatous involvement of bone marrow
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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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
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Experimentální: 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. |
Ostatní jména:
Ostatní jména:
Ostatní jména:
Ostatní jména:
Ostatní jména:
Ostatní jména:
Ostatní jména:
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Best Response Prior to Tandem Autologous Stem Cell Transplant
Časové okno: 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
|
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Response After Tandem Autologous Stem Cell Transplant
Časové okno: 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.
|
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Three-year Overall Survival
Časové okno: 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
Časové okno: 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.
|
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Best Response at 6 Months Post Tandem Autologous Stem Cell Transplant
Časové okno: 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
Časové okno: 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.
|
Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Spolupracovníci
Spolupracovníci
Vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: George Somlo, MD, City of Hope Medical Center
Publikace a užitečné odkazy
Obecné publikace
- 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.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Začátek studia
Primární dokončení (Aktuální)
Primární dokončení
Dokončení studie (Aktuální)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhadovaný)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Cévní onemocnění
- Kardiovaskulární choroby
- Novotvary
- Onemocnění imunitního systému
- Novotvary podle histologického typu
- Hematologická onemocnění
- Lymfoproliferativní poruchy
- Imunoproliferativní poruchy
- Hemostatické poruchy
- Paraproteinémie
- Poruchy krevních bílkovin
- Hemoragické poruchy
- Hemická a lymfatická onemocnění
- Mnohočetný myelom
- Novotvary, plazmatické buňky
- Peptidy
- Aminokyseliny, peptidy a proteiny
- Proteiny
- Sloučeniny síry
- Organické chemikálie
- Heterocyklické sloučeniny, 1 kruh
- Heterocyklické sloučeniny
- Heterocyklické sloučeniny, 2-prsten
- Heterocyklické sloučeniny, fúzované kroužek
- Terapeutika
- Chirurgické postupy, operativní
- Uhlovodíky, acyklické
- Uhlovodíky
- Biologické faktory
- Uhlohydráty
- Karboxylové kyseliny
- Transplantace
- Piperidiny
- Aminokyseliny
- Alkany
- Alkoholy
- Butylenglykoly
- Glykoly
- Mesyláty
- Alkanesulfonáty
- Alkanesulfonové kyseliny
- Kyseliny sulfonové
- Kyseliny síry
- Komponenty genomu
- Genom
- Genetické struktury
- Genetické jevy
- Fosforamidové hořčice
- Sloučeniny hořčice dusíku
- Hořčičné sloučeniny
- Uhlovodíky, halogenované
- Fosforamidy
- Organofosforové sloučeniny
- Mezibuněčné signalizační peptidy a proteiny
- Glykoproteiny
- Glykokonjugáty
- Transplantace buněk
- Terapie na bázi buněk a tkání
- Biologická terapie
- Fenylalanin
- Aminokyseliny, aromatické
- Aminokyseliny, cyklické
- Organofosfonáty
- Fthalimidy
- Kyseliny ftalové
- Kyseliny, karbocyklické
- Piperidony
- Isoindoly
- Faktory stimulující kolonie
- Růstové faktory hematopoetických buněk
- Cytokiny
- Transplantace kmenových buněk
- Interferon typu I.
- Interferony
- Transplantace hematopoetických kmenových buněk
- Difosfonáty
- Genové komponenty
- Geny
- DNA, intergenní
- Pamidronát
- Cyklofosfamid
- Melfalan
- Busulfan
- Thalidomid
- Interferon-alfa
- Faktor stimulující kolonie granulocytů
- Filgrastim
- Transplantace kmenových buněk periferní krve
- Introny
Další identifikační čísla studie
Další identifikační čísla studie
- 99021
- P30CA033572 (Grant/smlouva NIH USA)
- CHNMC-IRB-99021 (Jiný identifikátor: City of Hope Institutional Review Board)
- NCI-G99-1583 (Jiný identifikátor: National Cancer Institute)
- CDR0000067301 (Identifikátor registru: NCI PDQ)
Plán pro data jednotlivých účastníků (IPD)
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