Daratumumab for Chemotherapy-Refractory Minimal Residual Disease in T Cell ALL

NCT05289687 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: EA9213
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, the investigators are hypothesizing that daratumumab-hyaluronidase will effectively treat T-ALL in patients who have persistent or recurrent MRD following treatment with chemotherapy.

Conditions

T-cell Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (14)

• Complete Remission (CR)

  Requires that all of the following be present. * Peripheral Blood Counts * Neutrophil count ≥ 1,000/µL. * Platelet count ≥ 100,000/µL. * Reduced hemoglobin concentration or hematocrit has no bearing on remission status. * Leukemic blasts must not be present in the peripheral blood. * Bone Marrow Aspirate and Biopsy * Cellularity of bone marrow biopsy must be \> 20% with maturation of all cell lines. * ≤ 5% T lymphoblasts by flow cytometry. * Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present.

  Day 29

• Complete Remission (CR)

  Requires that all of the following be present. * Peripheral Blood Counts * Neutrophil count ≥ 1,000/µL. * Platelet count ≥ 100,000/µL. * Reduced hemoglobin concentration or hematocrit has no bearing on remission status. * Leukemic blasts must not be present in the peripheral blood. * Bone Marrow Aspirate and Biopsy * Cellularity of bone marrow biopsy must be \> 20% with maturation of all cell lines. * ≤ 5% T lymphoblasts by flow cytometry. * Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present.

  Day 64

• Complete Response with Partial Count Recovery (CRh)

  The same as for CR except with unsupported platelets \> 50,000/μL, hemoglobin \> 7 g/dL, and absolute neutrophil count \> 500/μL.

  Day 29

• Complete Response with Partial Count Recovery (CRh)

  The same as for CR except with unsupported platelets \> 50,000/μL, hemoglobin \> 7 g/dL, and absolute neutrophil count \> 500/μL.

  Day 64

• Complete Remission incomplete (CRi)

  All the same response criteria in peripheral blood and bone marrow as CR with the exception that there is incomplete platelet recovery (platelets \> 75,000/uL but \< 100,000/μL independent of platelet transfusions) or incomplete neutrophil count recovery \> 750/uL but \< 1000/μL.

  Day 29

• Complete Remission incomplete (CRi)

  All the same response criteria in peripheral blood and bone marrow as CR with the exception that there is incomplete platelet recovery (platelets \> 75,000/uL but \< 100,000/μL independent of platelet transfusions) or incomplete neutrophil count recovery \> 750/uL but \< 1000/μL.

  Day 64

• Minimal Residual Disease Negativity (MRD-)

  Bone marrow lymphoblast percent \< 0.01% (\< 10-4) by flow cytometry in a patient that fulfills count requirements for CR/CRh/CRi..

  Day 29

• Minimal Residual Disease Negativity (MRD-)

  Bone marrow lymphoblast percent \< 0.01% (\< 10-4) by flow cytometry in a patient that fulfills count requirements for CR/CRh/CRi..

  Day 64

• Morphologic Relapse

  Bone Marrow Aspirate and Biopsy * Presence of \> 5% T lympho-blasts, not attributable to another cause (e.g., bone marrow regeneration). * If there are no circulating blasts and the bone marrow contains 5% to 20% blasts, then a repeat bone marrow performed ≥ 1 week later documenting more than 5% blasts is necessary to meet the criteria for relapse.

  Day 29

• MRD Relapse

  • Relapse following MRD negativity is defined as bone marrow T lymphoblast percent ≥ 0.01% (10-4).

  Day 29

• Morphologic Relapse

  Bone Marrow Aspirate and Biopsy * Presence of \> 5% T lympho-blasts, not attributable to another cause (e.g., bone marrow regeneration). * If there are no circulating blasts and the bone marrow contains 5% to 20% blasts, then a repeat bone marrow performed ≥ 1 week later documenting more than 5% blasts is necessary to meet the criteria for relapse.

  Day 64

• MRD Relapse

  • Relapse following MRD negativity is defined as bone marrow T lymphoblast percent ≥ 0.01% (10-4).

  Day 64

• Refractory

  Failure to achieve MRD negativity as defined by bone marrow with CR/CRh/CRi with T lymphoblast percent ≥ 0.01% (10-4).

  Day 29

• Refractory

  Failure to achieve MRD negativity as defined by bone marrow with CR/CRh/CRi with T lymphoblast percent ≥ 0.01% (10-4).

  Day 64

Study Arms (1)

Course 1

EXPERIMENTAL

Daratumumab-hyaluronidase

Drug: Daratumumab / Hyaluronidase Injection

Interventions

Daratumumab / Hyaluronidase Injection DRUG

Daratumumab-hyaluronidase 1800mg/ 30,000 units once weekly for 4 doses on Days 1, 8, 15, and 22

Course 1

Eligibility Criteria

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

You may qualify if:

• Patient must have documented T cell ALL and must be in first or later hematologic CR or CRi after a minimum of 2 blocks of intensive chemotherapy.
• Patients in hematologic CR or CRi must have persistent or recurrent MRD ≥ 10-4.
• Institution must have received central MRD status test results confirming persistent or recurrent MRD ≥ 10-4 by flow cytometry.
• Patient may have undergone a prior allogeneic stem cell transplant, but patient may not have Grafts Versus Host Disease (GVHD) that requires ongoing immunosuppressive therapy. Patient may receive prednisone if the dose is ≤ 10 mg per day.
• Patient must have an ECOG performance status 0-2.
• All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 1 registration to rule out pregnancy.
• Patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and continue to 3 months after the last dose of protocol treatment. Patients must also agree to abstain from donating sperm, even if they have had a successful vasectomy, or donating eggs while on study treatment and for 3 months after the last dose of protocol treatment.
• Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.
• Patient must have adequate organ and marrow function as defined below (these labs must be obtained ≤ 7 days prior to Step 1 registration).
• Absolute neutrophil count (ANC) ≥ 750/μL
• Platelets ≥ 75,000/μL
• Total or Direct bilirubin ≤ 2 mg/dL
• AST(SGOT)/ALT(SGPT) ≤ 3.0 × institutional ULN
• Creatinine ≤ 1.5 x institutional ULN or Creatinine Clearance \> 30 ml/min
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.

You may not qualify if:

• Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used

Sponsors & Collaborators

• Janssen, LP: collaborator
• Eastern Cooperative Oncology Group: lead

Study Sites (1)

Northwestern

Chicago, Illinois, 60611, United States

RECRUITING

Related Publications (24)

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  PMID: 22442346 BACKGROUND

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  PMID: 23808872 BACKGROUND

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  BACKGROUND

• Wood BL, Winter SS, Dunsmore KP, Devidas M, Chen S, Asselin B, et al. Patients with early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL) have high levels of minimal residual disease (MRD) at the end of induction-a Children's oncology group (COG) study [abstract]. Blood. 2009;114.

  BACKGROUND

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  BACKGROUND

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

daratumumab; Hyaluronoglucosaminidase

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases

Study Officials

• Shira Dinner, MD

  Northwestern University

  STUDY CHAIR

Central Study Contacts

Shira Dinner, MD

CONTACT

312-695-6180; shira.dinner@nm.org

Talha Badar, MD

CONTACT

904-953-7556; badar.talha@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: This is a single arm study of daratumumab-hyaluronidase in T-ALL patients in morphologic CR with persistent or relapsed MRD. MRD will be assessed centrally for eligibility and response by flow cytometry. All patients will receive daratumumab-hyaluronidase once weekly for up to 4 doses during Course 1. .

Study Record Dates

• First Submitted: February 18, 2022
• First Posted: March 21, 2022
• Study Start: May 25, 2023
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (1)