Adoptive Transfer of Haplo-identical DLI for AML and MDS
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|ClinicalTrials.gov Identifier: NCT02046122|
Recruitment Status : Completed
First Posted : January 27, 2014
Results First Posted : July 18, 2018
Last Update Posted : December 3, 2020
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Myelodysplastic Syndrome||Drug: Idarubicin Drug: Cytarabine Biological: DLI||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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)|
|Study Start Date :||July 2014|
|Actual Primary Completion Date :||June 15, 2017|
|Actual Study Completion Date :||July 31, 2019|
Experimental: Idarubicin + Cytarabine + DLI
Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI)
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.
- Number of Subjects With Unacceptable Toxicity [ Time Frame: up to 8 weeks after last cell infusion ]
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)
- Disease Free Survival [ Time Frame: one year following adoptive transfer ]1 year disease free survival rate following adoptive transfer
- Overall Survival [ Time Frame: 2 years after completing therapy ]Number of participants alive 2 years after completing adoptive transfer therapy.
- Percentage of Subjects With Acute GVHD [ Time Frame: 8 weeks after last cell infusion ]Grade III or IV aGVHD of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days
- Percentage of Subjects With Unacceptable Toxicity [ Time Frame: 8 weeks after the last cell infusion ]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
- Rate of Efficacy [ Time Frame: 2 years after completing therapy ]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).
- Number of Participants With Immune Recovery [ Time Frame: up to 2 years after completing therapy ]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
- Number of Days to Hematopoietic Recovery [ Time Frame: 2 years after completion of therapy ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02046122
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Anthony Sung, MD||Duke University|