Clinical Trials /

Adoptive Transfer of Haplo-identical DLI for AML and MDS

NCT02046122

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: Pro00043247
  • NCT ID: NCT02046122

Conditions

  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome

Interventions

DrugSynonymsArms
IdarubicinIdarubicin + Cytarabine + DLI
CytarabineIdarubicin + Cytarabine + DLI
DLIIdarubicin + Cytarabine + DLI

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Idarubicin + Cytarabine + DLIExperimentalChemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI)
  • Idarubicin
  • Cytarabine

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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:55 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Subjects With Unacceptable Toxicity
Time Frame:up to 8 weeks after last cell infusion
Safety Issue:
Description: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)

Secondary Outcome Measures

Measure:Disease Free Survival
Time Frame:one year following adoptive transfer
Safety Issue:
Description:1 year disease free survival rate following adoptive transfer
Measure:Overall Survival
Time Frame:2 years after completing therapy
Safety Issue:
Description:Overall survival 2 years after completing adoptive transfer therapy
Measure:Percentage of Subjects With Acute GVHD
Time Frame:8 weeks after last cell infusion
Safety Issue:
Description:Grade III or IV aGVHD of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days
Measure:Percentage of Subjects With Unacceptable Toxicity
Time Frame:8 weeks after the last cell infusion
Safety Issue:
Description: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
Measure:Rate of Efficacy
Time Frame:2 years after completing therapy
Safety Issue:
Description:Efficacy as measured by the percentage of subjects with a complete remission.
Measure:Rate of Immune Recovery
Time Frame:2 years after completing therapy
Safety Issue:
Description: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
Measure:Rate of Hematopoietic Recovery
Time Frame:2 years after completion of therapy
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Duke University

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