Using daratumumab to treat very high-risk T-ALL

Daratumumab in Very High-Risk T-Lineage Acute Lymphoblastic Leukemia (ALL) Treated According to the ALL National Treatment Program (DARATALL-VHR)

This study is testing if adding daratumumab to a special chemotherapy plan can help adults with very high-risk T-lymphoblastic leukemia achieve better treatment results.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 31 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto (Academic / other)
• Drugs / interventions: chemotherapy, cyclophosphamide, daratumumab
• Locations: 3 sites (Firenze and 2 other locations)
• Trial ID: NCT06253637 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of daratumumab in combination with a pediatric-inspired chemotherapy regimen for adults diagnosed with very high-risk T-lymphoblastic leukemia (T-ALL). The study will assess whether this combination can increase the rate of minimal residual disease (MRD)-negative patients following induction therapy. Eligible participants will be treated according to the national treatment program, and the trial includes a safety run-in phase to monitor for adverse reactions. The study focuses on patients with specific immunophenotypes and high white blood cell counts, ensuring a targeted approach to treatment.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18-65 with a diagnosis of very high-risk T-ALL or T-Myeloid MPAL.

Not a fit: Patients with low-risk T-ALL or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with very high-risk T-ALL by increasing the rate of MRD negativity.

How similar studies have performed: While the use of daratumumab in this context is novel, previous studies have shown promising results with similar approaches in treating high-risk leukemias.

Eligibility criteria

Inclusion Criteria:

1. Age 18-65 years.
2. A diagnosis of T-ALL according to the 2022 International Consensus Classification (ICC) is required, either de novo or secondary to chemo-radiotherapy for another cancer. Pre-treatment with low-dose corticosteroids +/- cyclophosphamide in patients presenting with hyperleukocytosis is allowed.
3. Availability of fresh bone marrow (BM) (or peripheral blood (PB) in patients with hyperleukocytosis) samples to perform diagnostic procedures. ).
4. Bone marrow blast percentage at diagnosis ≥20%.
5. CD38 positivity on ALL blasts (any level of positivity).
6. ETP and near ETP at diagnosis according to internationally accepted criteria (appendix G) at diagnosis or other VHR T-ALL subtypes (WBC count \>100 x109/L; complex karyotype with ≥5 unrelated anomalies; other CD1a-negative immunophenotypes). T-Myeloid MPAL according to the 2022 ICC of Acute Leukemias of Ambiguous Lineage (appendix H) can also be eligible and considered as VHR.
7. Availability of full cytological, cytochemical, immunophenotypic, cytogenetic and molecular disease characterization according to the EGIL and WHO classifications.
8. An ECOG performance status 0-2, unless a performance of 3 is unequivocally caused by the disease itself, (and not by pre-existing comorbidities,) and is considered and/or documented to be reversible following the application of anti-leukemic therapy and appropriate supportive measures.
9. For females of childbearing potential, a negative pregnancy test must be documented. Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from enrollment through 12 months after the end of treatment.
10. Signed written informed consent according to ICH/E U/GCP and national local laws.

Exclusion Criteria:

1. Diagnosis of B-lineage ALL, and Ph+ ALL.
2. Down's syndrome.
3. Prior systemic chemotherapy for ALL (excluding cyclophosphamide during pre-phase).
4. Pre-existing, uncontrolled pathology such as heart failure (congestive/ischemic, acute myocardial infarction within the past 3 months, untreatable arrhythmias, NYHA classes III and IV), severe liver disease with serum direct bilirubin \>3 mg/dL (unless attributable to Gilbert' syndrome or ALL) and/or ALT \>5x upper normal limit (unless attributable to ALL), kidney function impairment with serum creatinine \>2 mg/dL (unless attributable to ALL), and severe neuropsychiatric disorder that impairs the patient's ability to understand and sign the informed consent, or to cope with the intended treatment plan. N.B. For altered liver and kidney function tests, eligibility criteria can be reassessed at 24-96 hours, following the institution of adequate supportive measures.
5. Presence of serious, active, uncontrolled infections.
6. A history of cancer that is not in a remission phase following surgery and/or radiotherapy and/or chemotherapy, with a life expectancy \<2 years.
7. Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.

Where this trial is running

Firenze and 2 other locations

• Ematologia AOU Careggi — Firenze, Italy (Recruiting)
• Ematologia P.O. Vito Fazzi - Lecce — Lecce, Italy (Recruiting)
• Ematologia AOU Policlinico Umberto I — Roma, Italy (Recruiting)

Study contacts

• Principal investigator: Sabina Chiaretti — University of Roma La Sapienza
• Study coordinator: Paola Fazi

Conditions T-Lymphocytic Leukemia, Acute