Recruitment

Recruitment Status
Recruiting
Estimated Enrollment
Same as current

Summary

Conditions
  • Minimal Residual Disease
  • Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes
  • Recurrent Adult Acute Myeloid Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
Type
Interventional
Phase
Phase 1Phase 2
Design
Allocation: N/AIntervention Model: Single Group AssignmentMasking: None (Open Label)Primary Purpose: Treatment

Participation Requirements

Age
Younger than 125 years
Gender
Both males and females

Description

PRIMARY OBJECTIVES: I. To evaluate safety and tolerability of daratumumab and escalating doses of donor lymphocyte infusions (DLI) in post-hematopoietic cell transplantation (HCT) patients with relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) transformed to AML (phase I). II....

PRIMARY OBJECTIVES: I. To evaluate safety and tolerability of daratumumab and escalating doses of donor lymphocyte infusions (DLI) in post-hematopoietic cell transplantation (HCT) patients with relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) transformed to AML (phase I). II. To evaluate overall response rate to daratumumab and DLI in patients with post-HCT relapsed AML and MDS (phase II). SECONDARY OBJECTIVES: I. To assess overall response rates in minimal residual disease (MRD) positive patients and in patients with overt morphological relapse. II. To assess MRD conversion rates from MRD positive to MRD negative. III. To determine the post-relapse 6-month overall response (OS) rates of patients with relapsed AML and MDS following allogeneic hematopoietic stem cell transplantation (allo-HSCT) who are treated with daratumumab. IV. To determine the rates of graft-versus-host disease (GVHD) (both grades II-IV and III-IV) and autoimmune side effects of daratumumab. V. To determine the post-relapse 6-month progression-free survival (PFS) rates of patients with relapsed AML and MDS following allo-HSCT who are treated with daratumumab. EXPLORATORY OBJECTIVES: I. To compare CD38 expression levels in myeloid blasts and interferon gamma (IFN-y) levels in plasma at the time of relapse before starting daratumumab and at progression or relapse after daratumumab. II. To compare peripheral blood T cell number and subsets (CD3, CD4, CD8, (CD38 expression on regulatory T cells [T-regs], CD4 and CD8), T regs, B-regulatory cells, natural killer (NK) cell numbers and bone marrow T cell subsets at the time of relapse before starting daratumumab, at the time of partial/complete response to daratumumab, and at the time of progression or relapse after daratumumab. III. To evaluate whether daratumumab has (i) direct anti-leukemia effects (ii) antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) and (III) immune modulation of autologous immune system (NK cells, T cells, T-regs, B-regulatory cells [B-regs], and myeloid-derived suppressor cells [MDSCS]) in AML. IV. To evaluate the effect of daratumumab on exosome content and clearance along with other soluble factors in AML. V. To evaluate serum interferon (IFN) levels pre-daratumumab, during and post-daratumumab. VI. To evaluate whether fratricide occurs in patients treated with daratumumab. OUTLINE: This is a phase I, dose escalation study of donor lymphocyte infusions followed by a phase II study. Participants receive daratumumab intravenously once a week for 8 weeks and donor lymphocyte infusion in weeks 3 or 4 in the absence of disease progression or unacceptable toxicity. Participants found to be in complete response (CR) at the end of 8 weeks may receive daratumumab IV once every 2 weeks for 8 weeks, and then once monthly for 6 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up for 1 year.

Tracking Information

NCT #
NCT03537599
Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Sumithira Vasu, MBBS Ohio State University Comprehensive Cancer Center