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

NCT03537599 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: OSU-17102NCI-2018-00616
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Safety and Feasibility Defined as the Establishment of the Appropriate Dose Level of Donor Lymphocyte Infusion When Given With a Fixed Dose of Daratumumab

  Up to 6 months

Secondary Outcomes (4)

• Rates of Complete Remission

  Up to 6 months

• Post-relapse Progression-free Survival

  At 6 months

• Post-relapse Overall Survival

  Up to 6 months

• Minimal Residual Disease (MRD) Conversion Rates

  Up to 6 months

Other Outcomes (13)

• Expression of CD38 on Bone Marrow

  Up to 6 months

• Expression of CD38 in Lymphocytes in Bone Marrow

  Baseline to 6 months

• Phenotypic Studies to Evaluate T Cell Exhaustion/Function

  Baseline to 6 months

Study Arms (1)

Treatment (DLI, daratumumab)

EXPERIMENTAL

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.

Biological: Daratumumab; Procedure: Donor Lymphocyte Infusion; Other: Laboratory Biomarker Analysis

Interventions

Daratumumab BIOLOGICAL

Given IV

Also known as: Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414

Treatment (DLI, daratumumab)

Donor Lymphocyte Infusion PROCEDURE

Given via infusion

Also known as: DLI, Donor Leukocyte Infusion

Treatment (DLI, daratumumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (DLI, daratumumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• AML relapse following Allo-HSCT (Morphological relapse, or MRD positive verified by flow cytometry, cytogenetics, and molecular mutations)
• Relapsed/Refractory AML must not be candidates for available therapies known to be effective for treatment of their AML.
• MDS transformed to AML following Allo-HCT
• Patients who received a 10/10 HLA-matched allogeneic HCT either from sibling donors or unrelated donors or atleast a 5/10 haploidentical transplant.
• Engraftment must have occurred as defined by platelet (PLT) count \> 20,000/µL and ANC
• Eastern Cooperative Oncology Group (ECOG) performance status \< 3
• Creatinine clearance \> 40 ml/min (calculated or measured)
• Aspartate aminotransferase (AST) \< 3 x upper limit of normal (ULN), alanine aminotransferase (ALT) \< 3 x ULN
• Total bilirubin \< 1.5 x ULN
• Off calcineurin inhibitors for at least 2 weeks
• Prednisone dose ≤ 20 mg/day
• Patients with proliferative disease can be cytoreduced with cytotoxic chemotherapy at Investigator discretion, but there should be at least a 14 day window between start of cytoreductive therapy and start of daratumumab
• Blast count ˂20K/day (hydrea use is allowed)

You may not qualify if:

• No demonstrable evidence of donor chimerism (˂ 55% donor CD3 or CD33 chimerism)
• Patients with a molecular mutation without chromosomal abnormalities or declining chimerisms (MRD status must be verified by surface marker and mutational analyses)
• Active graft-versus-host disease (GvHD) grades II-IV; prior acute GVHD could have occurred but resolved at time of initiation of daratumumab
• Extensive chronic GvHD requiring ongoing immunosuppression with calcineurin inhibitors
• Patients with FLT3+ AML or blast crisis CML who have not yet received post-transplant TKI therapy
• Active central nervous system (CNS) disease testicular disease
• EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.; seropositive for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy).
• Patients must not have moderate or severe persistent asthma within the past 2 years and must not have currently uncontrolled asthma of any classification.
• History of grade IV anaphylactic reaction to monoclonal antibody therapy
• Active autoimmune disease prior to transplant
• Concurrent use of any other investigational drugs

Sponsors & Collaborators

• Sumithira Vasu: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Neoplasm, Residual; Leukemia, Myeloid, Acute

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Dr. Sumithira Vasu
• Organization: The Ohio State University Comprehensive Cancer Center

Sumithira.Vasu@osumc.edu

614-293-9869

Study Officials

• Sumithira Vasu, MBBS

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 15, 2018
• First Posted: May 25, 2018
• Study Start: January 10, 2020
• Primary Completion: August 4, 2021
• Study Completion: February 3, 2022
• Last Updated: May 21, 2025
• Results First Posted: May 21, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)