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Combinaison de chimiothérapie, greffe de cellules souches périphériques, thérapie biologique, pamidronate et thalidomide pour le myélome multiple

15 octobre 2026 mis à jour par: City of Hope Medical Center

Melphalan et busulfan/cyclophosphamide séquentiels à haute dose suivis d'un sauvetage de cellules souches du sang périphérique, d'interféron/thalidomide et de pamidronate pour les patients atteints de myélome multiple

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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

77

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

1 seconde à 65 ans (Enfant, Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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 d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Biologique: interféron alfa recombinant
Autres noms:
  • IFN alpha-2B
  • Intron A
Médicament: cyclophosphamide
Autres noms:
  • Cytoxane
  • cytophosphane
Médicament: busulfan
Autres noms:
  • Busulfex
  • Myléran
Procédure: greffe de cellules souches du sang périphérique
Autres noms:
  • greffe de cellules progénitrices du sang périphérique
Biologique: filgrastim
Autres noms:
  • Neupogène
  • facteur de stimulation des colonies de granulocytes (G-CSF)
Médicament: melphalan
Autres noms:
  • Alkeran
  • Évoméla
Médicament: la thalidomide
Autres noms:
  • Thalidomid
  • Immunoprine
Médicament: pamidronate disodique
Autres noms:
  • acide pamidronique

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Best Response Prior to Tandem Autologous Stem Cell Transplant
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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.

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

City of Hope Medical Center

Collaborateurs

National Cancer Institute (NCI)

Les enquêteurs

  • Chercheur principal: George Somlo, MD, City of Hope Medical Center

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

  • 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.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

8 juillet 1999

Achèvement primaire (Réel)

9 janvier 2018

Achèvement de l'étude (Réel)

9 janvier 2018

Dates d'inscription aux études

Première soumission

10 décembre 1999

Première soumission répondant aux critères de contrôle qualité

26 janvier 2003

Première publication (Estimé)

27 janvier 2003

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

3 novembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

15 octobre 2026

Dernière vérification

1 octobre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 99021
  • P30CA033572 (Subvention/contrat des NIH des États-Unis)
  • CHNMC-IRB-99021 (Autre identifiant: City of Hope Institutional Review Board)
  • NCI-G99-1583 (Autre identifiant: National Cancer Institute)
  • CDR0000067301 (Identificateur de registre: NCI PDQ)

Plan pour les données individuelles des participants (IPD)

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Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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