A Study of Circulating Tumor DNA (ctDNA) Testing for People With B-Cell Lymphoma

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Enrolling; Phase 2

Conditions: Diffuse Large B Cell Lymphoma of Breast; Diffuse Large B Cell Lymphoma of Testis; Intravascular Large B-Cell Lymphoma; Stage IV High Grade B-Cell Lymphoma; DLBCL - Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma; Stage III High Grade B-Cell Lymphoma; Diffuse Large B Cell Lymphoma; Double Expressor DLBCL; HIV-associated Diffuse Large B Cell Lymphoma

Treatments: Diagnostic Test: Cerebral Spinal Fluid ctDNA

Study type: Interventional

Funder types: Other

Identifiers

NCT06736613

24-336

Details and patient eligibility

About

The purpose of this study is to find out how many people with B-cell lymphoma who are at high risk for central nervous system/CNS relapse test positive for cerebral spinal fluid/CSF ctDNA but test negative for CNS involvement using standard tests. The study will also look at how often CNS relapse happens in people with and without detected CSF ctDNA.

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed Informed Consent.

• Ability and willingness to comply with the requirements of the study protocol.

• Age ≥ 18 years old.

• Diagnosis of the following histologies according to the 2016 WHO Classification for Mature Lymphoid Neoplasms81 along with a specific high-risk criteria for CNS relapse if indicated as certain diagnoses in of themselves are high-risk alone:

  1. Diffuse Large B-cell Lymphoma (DLBCL) with CNS IPI score ≥ 4.
  2. Stage III/IV High Grade B-cell lymphoma (HGBCL) with MYC, BCL2, and/or BCL6 translocations
  3. Primary DLBCL of Breast
  4. Primary DLBCL of Testis
  5. Primary Cutaneous DLBCL, Leg Type
  6. Intravascular Large B-cell Lymphoma
  7. Stage III/IV HIV-associated DLBCL
  8. Double expressor DLBCL (co-expression of MYC ≥ 40% and BCL2 ≥ 50% without translocations) with a CNS IPI score ≥ 3
  9. DLBCL with the following extranodal involvement AND CNS IPI score ≥ 3:

  i. Adrenal ii. Breast iii. Bone Marrow with pathological overt morphological involvement iv. Epidural/Paraspinal v. Nasal/parasinus with local invasion such as bone destruction vi. Renal viii. Uterine ix. Testis xi. Skull involvement without direct invasion into CNS/brain parenchyma

• Transformed DLBCL from any indolent B-cell lymphoma is permitted (as long as there is no prior history of CNS involvement).

• Planned to receive standard chemoimmunotherapy.

• Patient is able to undergo lumbar puncture without any contraindications which include but are not limited to altered mental status, increased intracranial pressure due to any CNS lesion (mass, abscess), overlying skin infection at the site of LP, inability to safely access CSF due to lymphomatous involvement (i.e. epidural mass), or inability to hold antiplatelet or anticoagulation safely for the procedure to be performed.

• No systemic therapy prior to study enrollment for an aggressive B-cell lymphoma is permitted. Treatment for a history of indolent lymphoma is permitted. Systemic corticosteroids are permitted (must be ≤7 days and tapered down to prednisone ≤ 20 mg oral/day or steroid equivalent by first day of anthracycline treatment). Clinical exceptions in regards to steroid management can be made after discussion with PI.

• ECOG performance status of 0 to 2.

Exclusion criteria

• Active systemic therapy for another malignancy (other than indolent B-cell lymphoma) within 2 years; local/regional therapy with curative intent such as surgical resection or localized radiation within 2 years of treatment is permitted.
• Active concurrent malignancy with the exception of basal cell or localized squamous cell skin carcinoma, localized prostate cancer, or other localized carcinomas such as carcinoma in situ of cervix, breast, or bladder.
• Any uncontrolled illness that in the opinion of the investigator would preclude administration of curative intent chemoimmunotherapy (e.g. significant active infections, hypertension, angina, arrhythmias, pulmonary disease, or autoimmune dysfunction).
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 2 weeks prior to Cycle 1, Day 1.
• Psychiatric illness or social situations that would limit the patient's ability to tolerate and/or comply with study requirements.

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

Participants with Diffuse large B-cell lymphoma (DLBCL) i

Experimental group

Description:

Participants will be deemed clinically high-risk for CNS relapse. Participants will be considered to be high-risk for CNS relapse as determined by CNS-IPI score, pathological characteristics such as the presence of MYC, BCL2 and/or BCL6 translocations and specific extranodal involvement such as breast, renal, adrenal, nasopharyngeal, epidural/paraspinal involvement

Treatment:

Diagnostic Test: Cerebral Spinal Fluid ctDNA