- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT02046122
Adoptive Transfer of Haplo-identical DLI for AML and MDS
Safety and Efficacy of Chemotherapy Combined With Adoptive Transfer of Human Leukocyte Antigen (HLA)-Haploidentical Donor Lymphocyte Infusion (DLI) in Older Patients With Righ-Risk Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Réel)
Phase
- Phase 2
- La phase 1
Contacts et emplacements
Lieux d'étude
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North Carolina
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Durham, North Carolina, États-Unis, 27710
- Duke University Medical Center
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Subjects must have their diagnosis of high-risk AML or high-risk MDS confirmed by pathologic review of bone marrow biopsy according to WHO guidelines
Patients will be defined as high risk AML and thus eligible if they meet one or more of the following criteria:
- Secondary AML (from underlying MDS or therapy related)
- Presence of complex cytogenetic abnormalities (3 or more cytogenetic abnormalities), all monosomies, del 5q, del 7q, inv3, t(3;3), t(6;9), t(9;22), abn 11q23 (excluding t(9;11))
- Fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutation positive
- Age ≥ 65 years given poor outcomes even with favorable cytogenetics
- Patients will be defined as high risk MDS and thus eligible if they have a MD Anderson Comprehensive Cancer MDS Risk Score ≥9
- Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1,or 2; if ECOG 2, they must also have a Charlson comorbidity index of ≤5.
- Subjects must be 55 years of age or older
- Subjects should have a 3-5/6 HLA-matched related haploidentical donor who is evaluated and deemed able to provide DLI.
- Patient should be able to provide informed consent
- Subjects must have a multigated acquisition (MUGA) and /or ECHO or cardiac magnetic resonance imaging (MRI). The required minimum standards include MUGA or ECHO or cardiac MR showing an ejection fraction( EF) of 40%. Those with an EF 40-49% must also have a cardiologist consult and assist with management.
- Pulmonary function tests (PFTs) with diffusing capacity of lung for carbon monoxide (DLCO) are conditional for subjects at the discretion of the physician. The required minimum standards for those who have PFTs include DLCO of 40%. Those with DLCO of 40-49% must have a pulmonologist consult and assist with management.
- Subjects of all genders and races are eligible
Exclusion Criteria:
- Pregnant or lactating women.
- Patients with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol
- Patients with known active central nervous system (CNS) disease
- Patients with acute promyelocytic leukemia (FAB M3)
Plan d'étude
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: Idarubicin + Cytarabine + DLI
Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI)
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Eligible subjects will receive induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who experience no remission or partial remission will receive a second course of the identical induction chemotherapy. Cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who achieve a complete remission (CR) will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after the second consolidation. HLA-mismatched DLI will be administered Day 9, approximately 24-48 hours following completion of chemotherapy at a dose of 1x10^8 cluster of differentiation 3 (CD3+) cells; however, due to logistics of planning infusions with staffing, donor availability, weekends/holidays, etc., it may be necessary to postpone cell infusion up to 96 hours. Given the time constraints presented by the need to start induction chemotherapy as soon as possible, in some cases, it may not be logistically possible to administer cells with induction. In these cases, patients would just receive standard induction chemotherapy and cells would be administered after consolidation 1 in addition to consolidation 2 Subjects who achieve a CR will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after the second consolidation. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Number of Subjects With Unacceptable Toxicity
Délai: up to 8 weeks after last cell infusion
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Unacceptable toxicity is defined as: i. Grade III or IV acute GVHD (aGVHD) of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days; ii. Grade IV Common Terminology Criteria for Adverse Events (CTCAE) toxicity attributable to DLI (e.g. infusion reaction, as opposed to Grade IV CTCAE toxicity from chemotherapy) and lasting >7 days iii. Treatment-related mortality (TRM) |
up to 8 weeks after last cell infusion
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Disease Free Survival
Délai: one year following adoptive transfer
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1 year disease free survival rate following adoptive transfer
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one year following adoptive transfer
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Overall Survival
Délai: 2 years after completing therapy
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Number of participants alive 2 years after completing adoptive transfer therapy.
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2 years after completing therapy
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Percentage of Subjects With Acute GVHD
Délai: 8 weeks after last cell infusion
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Grade III or IV aGVHD of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days
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8 weeks after last cell infusion
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Percentage of Subjects With Unacceptable Toxicity
Délai: 8 weeks after the last cell infusion
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Grade IV CTCAE toxicity attributable to DLI (e.g.
infusion reaction, as opposed to Grade IV CTCAE toxicity from chemotherapy) and lasting >7 days, Grade III or IV aGVHD of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days, or death
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8 weeks after the last cell infusion
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Rate of Efficacy
Délai: 2 years after completing therapy
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Efficacy as measured by the number of subjects with a complete remission.
Responses were evaluated according to standard criteria defined by the National Comprehensive Cancer Network Guidelines for AML (www.nccn.org).
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2 years after completing therapy
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Number of Participants With Immune Recovery
Délai: up to 2 years after completing therapy
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Immune recovery determined by measurements of cytokine profiles, lymphocyte and natural killer (NK) enumeration and flow-based assays, measured prior to induction, prior to each round of consolidation, 8 weeks after the last cycle of consolidation, and every 3 months after treatment for up to 2 years
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up to 2 years after completing therapy
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Number of Days to Hematopoietic Recovery
Délai: 2 years after completion of therapy
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Hematopoietic recovery as measured by the date of the first of three consecutive laboratory values where the absolute neutrophil count (ANC) ≥ 500/μl , the date of the first of three consecutive laboratory values obtained on different days where the platelet count was > 20,000/μl without transfusion.
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2 years after completion of therapy
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Anthony Sung, MD, Duke University
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Tumeurs par type histologique
- Tumeurs
- Maladies de la moelle osseuse
- Maladies hématologiques
- Conditions précancéreuses
- Syndromes myélodysplasiques
- Leucémie
- Leucémie myéloïde
- Leucémie, myéloïde, aiguë
- Préleucémie
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Inhibiteurs d'enzymes
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Inhibiteurs de la topoisomérase II
- Inhibiteurs de la topoisomérase
- Antibiotiques, Antinéoplasiques
- Cytarabine
- Idarubicine
Autres numéros d'identification d'étude
- Pro00043247
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