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Phase I/II Study of 5-Azacytidine With Ara-C in Patients With Relapsed/Refractory Acute Myelogenous Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)

26 juillet 2012 mis à jour par: M.D. Anderson Cancer Center

Randomized Phase I/II Study of 5-Azacytidine in Combination With Cytosine Arabinoside in Patients With Relapsed/Refractory Acute Myelogenous Leukemia or High Risk Myelodysplastic Syndrome - "SPORE"

The goal of this clinical research study is to find the highest tolerable dose of Azacytidine (5-azacytidine) combined with cytosine arabinoside (ara-C) for the treatment of patients with relapsed and/or refractory Acute Myeloid Leukemia (AML) or high-risk Myelodysplastic Syndrome (MDS). The safety and effectiveness of this treatment combination will also be studied.

Aperçu de l'étude

Description détaillée

5-azacytidine is designed to "turn off" the growth of cancer cells. This may be increased by ara-C, which is designed to kills leukemia cells by helping to stop the cells from dividing.

If you are found to be eligible to take part in this study, you will be assigned to a treatment group. You will be randomly assigned (as in the toss of a coin) to one of the 4 treatment groups. The first 3 to 6 patients will be assigned to Group 1. If no serious side effects are experienced, the next 3 to 6 patients will be assigned to Group 2. If no serious side effects are experienced, the next 3 to 6 patients will be assigned to Group 3. If no serious side effects are experienced, the next 3 to 6 patients will be assigned to Group 4.

If you are in Group 1, you will receive low-dose 5-azacytidine as an infusion by vein over 20 to 30 minutes every day for 7 days. You will also receive low-dose ara-C as a continuous infusion by vein for 7 days.

If you are in Group 2, you will receive high-dose 5-azacytidine as an infusion by vein over 20 to 30 minutes every day for 7 days. You will also receive low-dose ara-C as a continuous infusion by vein for 7 days.

If you are in Group 3, you will receive low-dose 5-azacytidine as an infusion by vein over 20 to 30 minutes every day for 7 days. You will also receive high-dose ara-C as a continuous infusion by vein for 3 days (if you are 65 years of age or older) or for 4 days (if you are younger than 65 years of age).

If you are in Group 4, you will receive high-dose 5-azacytidine as an infusion by vein over 20 to 30 minutes every day for 7 days. You will also receive high-dose ara-C as a continuous infusion by vein for 3 days (if you are 65 years of age or older) or for 4 days (if you are younger than 65 years of age).

Each group's treatment will be repeated every 4 to 8 weeks (this is considered 1 cycle of treatment), depending on your blood counts and how well your bone marrow is recovering. You will receive at least 2 cycles of treatment. You will continue to receive treatment, unless your disease gets worse or if you experience intolerable side effects. If your disease gets worse or you experience intolerable side effects, you may be taken off this study.

This is an investigational study. 5-azacytidine has been approved by the FDA for the treatment of MDS. Ara-C has been approved by the FDA for the treatment of AML. Up to 80 patients will take part in this study. All will be enrolled at M. D. Anderson.

Type d'étude

Interventionnel

Inscription (Réel)

36

Phase

  • Phase 2
  • La phase 1

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

    • Texas
      • Houston, Texas, États-Unis, 77030
        • U.T.M.D. Anderson 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

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  1. Patients must have histologically confirmed Acute Myeloid Leukemia (AML) or high risk and previously treated Myelodysplastic Syndrome (MDS).
  2. Patients with (1) refractory disease or (2) first relapse within 6 months of therapy or (3) 2nd or more of relapse of Acute Myelogenous Leukemia (AML) or high risk Myelodysplastic Syndrome MDS will be considered for the study.
  3. Patients must have been off chemotherapy for 4 weeks prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease.
  4. Age >=18 years. Deoxyribonucleic acid (DNA) methylation plays a significant role in development, and the effects of azacitidine in children are not well described.
  5. Patients must have normal organ as defined: Total bilirubin <2 mg, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) <2.5 x institutional upper limit of normal, Creatinine <2 mg
  6. Ability to understand and the willingness to sign a written informed consent document.
  7. Women of child bearing potential must have a negative serum pregnancy test prior to azacitidine treatment.
  8. Women of child bearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with azacytidine.
  9. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

Exclusion Criteria:

  1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier, unless there is evidence of rapidly progressive disease. Patients may have received hydroxyurea prior to entering the study.
  2. Patients may not be receiving any other investigational agents for their leukemias.
  3. Patients with active brain or meningeal disease should be excluded.
  4. Known or suspected hypersensitivity to azacitidine or mannitol
  5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
  6. Pregnant women are excluded from this study because azacitidine is a Deoxyribonucleic acid (DNA) methyltransferase inhibitor which has teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with azacitidine, breastfeeding should be discontinued if the mother is treated with azacitidine.

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: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Low-Dose Ara-C + AZA-Level 0

Group 1 = Low-Dose Ara-C + Azacitidine-Level 0

Low-Dose Ara-C: 100 mg/m^2 Daily continuous intravenous infusion (CIV) for 7 days Azacitidine (AZA): 37.5 mg/m^2 intravenous (IV) Over 20-30 minutes Daily for 7 Days

Group 1 and 3 at Level 0 = 37.5 mg/m^2 IV Over 20-30 minutes Daily for 7 Days Group 2 and 4 at Level 1 = 75.0 mg/m^2 IV Over 20-30 minutes Daily for 7 days
Autres noms:
  • Vidaza

Group 1 and 2 at Low-Dose = 100 mg/m^2 Daily continuous intravenous infusion (CIV) for 7 days

Arms 3 and 4 at High-dose = 1 g/m^2 Daily CIV for 4 days (age<65 years) or 3 days (age>=65 years)

Autres noms:
  • Cytosar-U
  • la cytarabine
  • cytosine Arabinoside
Expérimental: Low-Dose Ara-C + AZA-Level 1

Group 2 = Low-Dose Ara-C + Azacitidine-Level 1

Low-Dose Ara-C: 100 mg/m^2 Daily continuous intravenous infusion (CIV) for 7 days AZA: Level 1 = 75.0 mg/m^2 IV Over 20-30 minutes Daily for 7 days

Group 1 and 3 at Level 0 = 37.5 mg/m^2 IV Over 20-30 minutes Daily for 7 Days Group 2 and 4 at Level 1 = 75.0 mg/m^2 IV Over 20-30 minutes Daily for 7 days
Autres noms:
  • Vidaza

Group 1 and 2 at Low-Dose = 100 mg/m^2 Daily continuous intravenous infusion (CIV) for 7 days

Arms 3 and 4 at High-dose = 1 g/m^2 Daily CIV for 4 days (age<65 years) or 3 days (age>=65 years)

Autres noms:
  • Cytosar-U
  • la cytarabine
  • cytosine Arabinoside
Expérimental: High-Dose Ara-C + AZA-Level 0
Group 3 = High-Dose Ara-C + Azacitidine-Level 0 High-dose Ara-C: 1 g/m^2 Daily CIV for 4 days (age<65years) or 3 days (age>=65years) AZA: 37.5 mg/m^2 IV Over 20-30 minutes Daily for 7 Days
Group 1 and 3 at Level 0 = 37.5 mg/m^2 IV Over 20-30 minutes Daily for 7 Days Group 2 and 4 at Level 1 = 75.0 mg/m^2 IV Over 20-30 minutes Daily for 7 days
Autres noms:
  • Vidaza

Group 1 and 2 at Low-Dose = 100 mg/m^2 Daily continuous intravenous infusion (CIV) for 7 days

Arms 3 and 4 at High-dose = 1 g/m^2 Daily CIV for 4 days (age<65 years) or 3 days (age>=65 years)

Autres noms:
  • Cytosar-U
  • la cytarabine
  • cytosine Arabinoside
Expérimental: High-Dose Ara-C + AZA-Level 1

Group 4 = High-Dose Ara-C + Azacitidine-Level 1

High-dose Ara-C: 1 g/m^2 Daily CIV for 4 days (age<65years) or 3 days (age>=65 years) AZA:Level 1 = 75.0 mg/m^2 IV Over 20-30 minutes Daily for 7 days

Group 1 and 3 at Level 0 = 37.5 mg/m^2 IV Over 20-30 minutes Daily for 7 Days Group 2 and 4 at Level 1 = 75.0 mg/m^2 IV Over 20-30 minutes Daily for 7 days
Autres noms:
  • Vidaza

Group 1 and 2 at Low-Dose = 100 mg/m^2 Daily continuous intravenous infusion (CIV) for 7 days

Arms 3 and 4 at High-dose = 1 g/m^2 Daily CIV for 4 days (age<65 years) or 3 days (age>=65 years)

Autres noms:
  • Cytosar-U
  • la cytarabine
  • cytosine Arabinoside

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Number of Participants With Complete Remission
Délai: 6 weeks
Clinical response is determined by achievement of a complete remission (CR) as judged by morphological criteria (< 1% blasts in bone marrow with neutrophil recovery) according to International Working Group (IWG) criteria.
6 weeks

Collaborateurs et enquêteurs

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

Collaborateurs

Les enquêteurs

  • Chercheur principal: Jean-Pierre Issa, MD, M.D. Anderson Cancer 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.

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

1 décembre 2005

Achèvement primaire (Réel)

1 octobre 2009

Achèvement de l'étude (Réel)

1 octobre 2009

Dates d'inscription aux études

Première soumission

5 décembre 2007

Première soumission répondant aux critères de contrôle qualité

5 décembre 2007

Première publication (Estimation)

6 décembre 2007

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

1 août 2012

Dernière mise à jour soumise répondant aux critères de contrôle qualité

26 juillet 2012

Dernière vérification

1 juillet 2012

Plus d'information

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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