Clinical trial NCT02046122: Adoptive Transfer of Haplo-identical DLI for AML and MDS
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndrome
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2014-01-27
Enrollment: 19
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary hypothesis is that chemotherapy followed by donor lymphocyte infusion (DLI) from HLA-haploidentical donors is a safe procedure that will not cause Graft versus Host Disease (GVHD) or increased treatment-related mortality. The Investigator further believes that this will improve outcomes of elderly patients with high-risk AML or MDS compared to chemotherapy alone, and that that this benefit will be even greater in donor-recipient pairs that share maternal-fetal microchimerism or non-inherited maternal antigen (NIMA) mismatch. A large part of this trial will include immune function assays as well as assessments of efficacy, toxicity, and GVHD. Because this therapy may be a tolerable alternative to allogeneic hematopoietic stem cell transplantation (alloHSCT) for elderly patients, the Investigator will validate functional measurements (e.g. Comprehensive Geriatric Assessment (CGA)) with biologic correlates (cytokine and genomic profiles) and clinical outcomes.


Eligibility criteria: Inclusion Criteria:

1. 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
2. Patients will be defined as high risk AML and thus eligible if they meet one or more of the following criteria:

   1. Secondary AML (from underlying MDS or therapy related)
   2. 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))
   3. Fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutation positive
   4. Age ≥ 65 years given poor outcomes even with favorable cytogenetics
3. Patients will be defined as high risk MDS and thus eligible if they have a MD Anderson Comprehensive Cancer MDS Risk Score ≥9
4. 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.
5. Subjects must be 55 years of age or older
6. Subjects should have a 3-5/6 HLA-matched related haploidentical donor who is evaluated and deemed able to provide DLI.
7. Patient should be able to provide informed consent
8. 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.
9. 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.
10. Subjects of all genders and races are eligible

Exclusion Criteria:

1. Pregnant or lactating women.
2. Patients with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol
3. Patients with known active central nervous system (CNS) disease
4. Patients with acute promyelocytic leukemia (FAB M3)

Primary outcomes:
measure: Number of Subjects With Unacceptable Toxicity
timeFrame: up to 8 weeks after last cell infusion
Secondary outcomes:
measure: Disease Free Survival
timeFrame: one year following adoptive transfer
measure: Overall Survival
timeFrame: 2 years after completing therapy
measure: Percentage of Subjects With Acute GVHD
timeFrame: 8 weeks after last cell infusion
measure: Percentage of Subjects With Unacceptable Toxicity
timeFrame: 8 weeks after the last cell infusion
measure: Rate of Efficacy
timeFrame: 2 years after completing therapy
measure: Number of Participants With Immune Recovery
timeFrame: up to 2 years after completing therapy
measure: Number of Days to Hematopoietic Recovery
timeFrame: 2 years after completion of therapy
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Anthony Sung, MD
role: PRINCIPAL_INVESTIGATOR
References: