NCT03537599

Daratumumab and Donor Lymphocyte Infusion in Treating Participants With Relapsed Acute Myeloid Leukemia After Stem Cell Transplant

Phase I/II Clinical Trial of Daratumumab and Donor Lymphocyte Infusion in Patients With Relapsed Acute Myeloid Leukemia Post-Allogeneic Hematopoietic Stem Cell Transplant

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 4 (actual)
• Sponsor: Sumithira Vasu · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of donor lymphocyte infusions when given together with daratumumab and to see how well they work in treating participants with acute myeloid leukemia that has come back after a stem cell transplant. A donor lymphocyte infusion is a type of therapy in which lymphocytes (white blood cells) from the blood of a donor are given to a participant who has already received a stem cell transplant from the same donor. The donor lymphocytes may kill remaining cancer cells. Monoclonal antibodies, such as daratumumab, may interfere with the ability of cancer cells to grow and spread. Giving daratumumab and donor white blood cells may work better in treating participants with acute myeloid leukemia.

Detailed 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. 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.

Conditions

• Minimal Residual Disease
• Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes
• Recurrent Adult Acute Myeloid Leukemia
• Recurrent Childhood Acute Myeloid Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	Daratumumab	Given IV
PROCEDURE	Donor Lymphocyte Infusion	Given via infusion
OTHER	Laboratory Biomarker Analysis	Correlative studies

Timeline

• Start date: 2020-01-10
• Primary completion: 2021-08-04
• Completion: 2022-02-03
• First posted: 2018-05-25
• Last updated: 2025-05-21
• Results posted: 2025-05-21

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study