Daratumumab to clear leftover T‑cell acute lymphoblastic leukemia

Daratumumab for Minimal Residual Disease Eradication in T-Acute Lymphoblastic Leukemia - A Phase 2 Study

This trial will try daratumumab given by IV to see if it can clear leftover cancer (MRD) in adults with T‑ALL who remain MRD‑positive after two induction cycles.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Tata Memorial Centre (Academic / other)
• Drugs / interventions: chemotherapy, Daratumumab
• Locations: 1 site (Navi Mumbai, Maharashtra)
• Trial ID: NCT07021677 on ClinicalTrials.gov

What this trial studies

Adults (18–65) with newly diagnosed T‑ALL who are MRD positive (≥0.01%) after two phases of induction chemotherapy and whose disease expresses CD38 will receive intravenous daratumumab at 16 mg/kg. Participants get two weekly doses and will have a bone marrow MRD test one week after the second dose; patients who remain MRD positive may receive two additional weekly doses with repeat MRD testing. The trial tracks whether patients convert to MRD negativity after two or four doses, monitors safety and adverse events, and follows progression or death up to one year. Outcomes include MRD conversion rates, one‑year progression/death risk, and treatment tolerability.

Who should consider this trial

Good fit: Adults 18–65 with newly diagnosed T‑ALL (including ETP‑ALL) who are MRD positive (≥0.01%) after two induction phases, have CD38‑positive disease, and ECOG performance status ≤2 are the intended participants.

Not a fit: Patients without CD38 expression, with persistent positive CSF or uncontrolled CNS/testicular disease, or those with active systemic infection or severe organ dysfunction are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, daratumumab could turn MRD‑positive T‑ALL patients MRD‑negative and potentially lower their risk of relapse.

How similar studies have performed: Daratumumab is an approved and effective drug in multiple plasma‑cell disorders and has limited case/series data in some T‑cell neoplasms, but its use specifically to clear MRD in T‑ALL is largely untested in formal trials.

Eligibility criteria

Inclusion Criteria:

1. Adults ≥18 - ≤65 years of age
2. Baseline diagnosis of T-ALL, including ETP-ALL
3. MRD positive (≥0.01%) disease (by flow-cytometry) assessed on BM after two phases of induction chemotherapy in CR-1
4. CD38 positive
5. Eastern cooperative oncology group (ECOG) performance status ≤2
6. Acceptable liver functions, as specified below:

   Total bilirubin \<2 times upper limit of normal (ULN); Aspartate transaminase (AST;SGOT), alanine transaminase (ALT;SGPT) \<3 ULN
7. Subject ready to sign an informed consent form
8. Patients with baseline CSF cytology positive, but who have cleared CSF by either modality (cytology or flow cytometry)

Exclusion Criteria:

1. T-LBL (T-lymphoblastic lymphoma) without BM involvement
2. Patients with persistently positive CSF cytology after two phases of induction or baseline testicular involvement
3. Patients with symptomatic obstructive airway disease, as per assessing clinician
4. Presence of an active systemic infection, as per assessing clinician
5. New York Heart Association (NYHA) Class III or IV cardiac disease, or left ventricular ejection fraction \<40%
6. Human immunodeficiency virus (HIV) positive.
7. Pregnant or breastfeeding female
8. HBsAg positive or HBV-DNA positivity

Where this trial is running

Navi Mumbai, Maharashtra

• Dr.Sumeet Mirgh — Navi Mumbai, Maharashtra, India (Recruiting)

Study contacts

• Principal investigator: Sumeet Mirgh, MD, DM — Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) Tata Memorial Centre
• Study coordinator: Sumeet Mirgh, MD, DM

Conditions T Acute Lymphoblastic Leukemia; daratumumab; T-Acute lymphoblastic leukemia; minimal residual disease; MRD; Post induction MRD