A Phase II Study of Daratumumab-Hyaluronidase for Chemotherapy-Relapsed/Refractory Minimal Residual Disease (MRD) in T Cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL/T-LBL)

By Shira Dinner, MD

T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) are rare, aggressive hematologic malignancies arising from early T-cell progenitors. The historical treatment approach is chemotherapy and possibly a stem cell transplant. However, relapse often occurs during active therapy, and salvage rates are poor due to limited treatment options. Whether T-ALL and T-LBL represent a single disease or two different diseases is a matter of current scientific debate. Nonetheless, more effective treatments to increase relapse-free survival and overall survival rates for T-ALL/T-LBL are needed.

EA9213 is a single-arm phase 2 study testing if the monoclonal antibody daratumumab-hyaluronidase will effectively eliminate minimal residual disease (MRD) in patients with T-ALL or T-LBL. Daratumumab-hyaluronidase is already approved by the US Food and Drug Administration (FDA) for multiple myeloma and light chain amyloidosis.

The study’s primary objective is to evaluate the rate of complete MRD response by flow cytometry after 4 weekly doses of daratumumab-hyaluronidase among patients with MRD-positive T-ALL or T-LBL. These patients may be in morphologic complete remission (CR), complete remission with incomplete hematologic recovery (CRi), or complete response with partial hematologic count recovery (CRh).

Amendment #2 (v.02/24/25) was recently activated, and includes several key changes to the eligibility criteria and treatment plan:

Eligibility:

• The trial now includes:
  • Patients with T-cell lymphoblastic lymphoma (T-LBL)
  • Patients in complete response with partial count recovery (CRh)
  • Pediatric patients ≥ 12 years of age
• The protocol reflects updates to distinguish pediatric and adult-specific criteria, requirements, procedures, and treatment details

Treatment Planning:

• Treatment must start within 14 days of Step 1 registration (previously within 14 days of receiving central MRD results)
• Nelarabine and calaspargase pegol have been added to study treatment options
• New dose modification specifications were added for high-dose cytarabine, methotrexate, and nelarabine
• Patients will discontinue treatment if MRD positive by MRD, or clonoSEQ if they enrolled with clonoSEQ positive results, after Day 64
• Updates have been made to definitions of CR, CRi, CRh, MRD negativity, relapse, and refractory disease
• Updates have been made to daratumumab ordering procedures and information

This is not a complete list of all changes to the protocol; please review the updated protocol carefully for complete details to avoid protocol deviations. Study resources have been revised to reflect Amendment #2, and are available for download at CTSU.org or on the EA9213 Educational Materials page.

Learn more about the EA9213 trial at ecog-acrin.org.

Dr. Dinner (Northwestern University) is the study chair for this trial. Dr. Talha Badar (Mayo Clinic Florida) is the study co-chair and Dr. Teena Bhatla (Robert Wood Johnson Barnabas Health) from the Children’s Oncology Group is the pediatric study co-chair.