T-Cell Lymphoma Clinical Trials — 2026 Pipeline

Active Phase 2 and Phase 3 recruiting trials — T-cell lymphoma (March 2026)

The table below reflects key recruiting and active trials on ClinicalTrials.gov for PTCL, CTCL, ALCL, AITL, and NK/T-cell lymphoma as of March 2026. DataLookout monitors for new registrations and status changes daily across all T-cell lymphoma subtypes.

Sources: ClinicalTrials.gov. DataLookout monitors for new registrations and status updates daily. Table reflects recruiting and active trials as of March 2026.

What DataLookout monitors in T-cell lymphoma

T-cell lymphoma is a molecularly and clinically heterogeneous disease family. DataLookout tracks all major subtypes and their disease-specific biomarkers across ClinicalTrials.gov, monitoring new registrations, status changes, and result postings daily. Subtypes covered include:

• PTCL-NOS (peripheral T-cell lymphoma, not otherwise specified) — the most common PTCL subtype in Western populations; broadly CD30-variable, treated with CHOP-based or BV+CHP regimens
• AITL (angioimmunoblastic T-cell lymphoma) — Tfh-cell origin; near-universal TET2/DNMT3A mutations; IDH2 R172 (~25%), RHOA G17V (~60%); high sensitivity to epigenetic-targeting combinations
• ALCL ALK+ (anaplastic large cell lymphoma, ALK-positive) — most favorable PTCL prognosis; CD30 universally positive; ALK fusion (most commonly NPM1-ALK) drives constitutive JAK/STAT3 and PI3K activation
• ALCL ALK− (ALK-negative ALCL) — CD30-positive but lacks ALK rearrangement; inferior prognosis vs. ALK+; DUSP22 and TP63 rearrangements define molecular subsets with distinct outcomes; BV+CHP is standard front-line
• CTCL / Mycosis Fungoides (MF) — primary cutaneous T-cell malignancy; CD4+/CD8− malignant T-cell epidermotropism; CCR4-expressing tumor cells in majority of cases; skin-directed therapy (early stages) vs. systemic therapy (advanced/transformed)
• Sézary Syndrome (SS) — leukemic variant of CTCL with circulating Sézary cells; high CCR4 expression; mogamulizumab FDA-approved; extracorporeal photopheresis remains a standard systemic option
• NK/T-cell lymphoma (ENKTL) — EBV-driven; primarily extranodal (nasal cavity, GI tract); anthracycline-resistant (MDR1); L-asparaginase backbone; PD-L1 overexpression drives PD-1 inhibitor sensitivity
• Hepatosplenic T-cell lymphoma (HSTCL) — rare, aggressive gamma-delta or alpha-beta T-cell lymphoma; no standard salvage regimen; clinical trial participation strongly recommended at diagnosis

Treatment landscape: front-line PTCL

CHOP and CHOEP: the historical backbone

CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) has been the default front-line chemotherapy backbone for PTCL subtypes for decades, despite producing inferior outcomes compared to its performance in aggressive B-cell lymphomas (DLBCL). For most PTCL subtypes, CHOP-based regimens achieve complete response (CR) rates of 40–60%, but 5-year PFS is only 20–30% due to high relapse rates. The addition of etoposide (CHOEP) improves outcomes in younger, fit patients — particularly in ALK+ ALCL — and is standard at many European and academic centers for patients under 60 with normal LDH. However, CHOEP has not demonstrated superiority over CHOP in randomized trials in PTCL overall.

Brentuximab vedotin + CHP: the CD30-positive standard of care

The landmark ECHELON-2 Phase 3 trial (NCT01777152) enrolled 452 patients with CD30-positive PTCL (ALCL, PTCL-NOS with CD30 ≥10%, AITL) and randomized them to brentuximab vedotin + CHP (removing vincristine to reduce peripheral neuropathy) versus CHOP. BV + CHP demonstrated a significantly improved PFS: median 48.2 months versus 20.8 months for CHOP (HR 0.71, p=0.011), as well as improved overall survival at 5-year follow-up. This led to FDA approval of BV + CHP in front-line CD30-positive PTCL and established CD30 IHC (using a ≥10% cutoff) as a mandatory diagnostic test in newly diagnosed systemic PTCL.

For ALCL — where CD30 is universally expressed at high levels — BV + CHP is now the unambiguous standard. For PTCL-NOS and AITL (where CD30 is expressed variably), the ECHELON-2 subgroup data support BV + CHP in CD30-positive cases, though the benefit size varies by subtype. The commercial and BD implication is clear: any sponsor developing a front-line PTCL regimen must either demonstrate superiority over BV + CHP (in CD30-positive disease) or position their drug in the CD30-negative PTCL setting where CHOP remains the comparator.

Approved agents: mogamulizumab, romidepsin, belinostat

Mogamulizumab (Poteligeo, Kyowa Kirin)

Mogamulizumab is an afucosylated humanized anti-CCR4 IgG1 antibody that depletes CCR4-expressing T cells via enhanced ADCC. CCR4 (CC chemokine receptor 4) is a homing receptor expressed on type 2 helper T cells (Th2) and regulatory T cells (Tregs), and is overexpressed on malignant T cells in the majority of CTCL (~90%) and a significant subset of PTCL (~30–40%, particularly PTCL-NOS and AITL).

Mogamulizumab is FDA-approved in two settings: (1) relapsed/refractory mycosis fungoides and Sézary syndrome, based on the Phase 3 MAVORIC trial (NCT01728805), which demonstrated PFS of 7.7 months versus 3.1 months with vorinostat (HR 0.53, p<0.0001); and (2) relapsed/refractory CCR4-positive PTCL based on the MOGAMULIZUMAB-1003 study, which showed an ORR of ~35% and a CR rate of ~14% in heavily pre-treated CCR4-positive PTCL. The drug's dual mechanism — direct tumor cell killing plus Treg depletion in the tumor microenvironment — has motivated combinations with PD-1 checkpoint inhibitors (NCT04128501), with the hypothesis that Treg depletion by mogamulizumab potentiates PD-1 blockade efficacy.

Romidepsin and belinostat (HDAC inhibitors)

Romidepsin (Istodax, BMS) is a bicyclic depsipeptide class I HDAC inhibitor approved in 2011 for relapsed/refractory PTCL and CTCL. In PTCL, its approval was based on a Phase 2 study (NCT00426764) showing an ORR of 25–38% in relapsed disease, with a CR rate of ~15%. Belinostat (Beleodaq, Acrotech) is a hydroxamate pan-HDAC inhibitor approved in 2014 based on the BELIEF Phase 2 trial (NCT01024998), which showed an ORR of 25.8% (CR 10.8%) in relapsed/refractory PTCL. Both agents produce responses in approximately one-quarter of heavily pre-treated patients, but responses are generally not durable as monotherapy.

The most important current investigation of HDAC inhibitors in PTCL is in AITL-specific combinations. Given AITL's near-universal TET2 and DNMT3A mutation burden, the combination of a hypomethylating agent (azacitidine, which partially restores TET2-like function via DNA demethylation) with an HDAC inhibitor (romidepsin, which addresses the HDAC compensatory pathway) has a strong mechanistic rationale. Phase 2 data from azacitidine + romidepsin in PTCL/AITL show ORRs of 55–65% in AITL-enriched cohorts — substantially higher than either agent alone — positioning this combination as a leading investigational approach for relapsed AITL.

Emerging pipeline: duvelisib, cobomarsen, and bispecifics

Duvelisib (Copiktra, Secura Bio) — PI3K-delta/gamma in PTCL

Duvelisib is an oral dual inhibitor of PI3K-delta (lymphocyte-expressed) and PI3K-gamma (myeloid/T-cell-expressed). PI3K-delta/gamma dual inhibition is particularly suited to PTCL: PI3K-delta is activated downstream of BCR/TCR signaling in malignant T cells, while PI3K-gamma inhibition depletes immunosuppressive tumor-associated macrophages in the lymphoma microenvironment. The Phase 2 PRIMO trial (NCT03534505) evaluated duvelisib in relapsed/refractory PTCL and reported an ORR of ~42%, with activity across multiple subtypes (PTCL-NOS, AITL, ALCL). Median duration of response was approximately 6.3 months. The FDA granted duvelisib Breakthrough Therapy designation in T-cell lymphoma, and the PRIMO data supported an NDA submission, though regulatory review is ongoing as of 2026. For BD teams, duvelisib represents the most advanced oral PI3K agent in PTCL and a potential future combination partner for front-line or maintenance strategies.

Cobomarsen (MRG-106) — miR-155 inhibitor in CTCL

Cobomarsen is a first-in-class antisense oligonucleotide inhibitor of microRNA-155 (miR-155), an oncogenic microRNA that is overexpressed in CTCL (particularly MF), DLBCL, and other lymphoid malignancies. miR-155 promotes lymphoma cell survival by suppressing multiple tumor suppressor targets including SHIP1, SOCS1, and PTP1B. The Phase 2 SOLAR trial (NCT03768505) evaluated cobomarsen in relapsed/refractory MF, representing the first clinical validation of miRNA-targeting in a hematologic malignancy. miRagen Therapeutics' program generated proof-of-concept for this mechanism, though development timelines and regulatory strategy have evolved. For medical affairs and BD professionals, cobomarsen is a landmark program in epigenetic/post-transcriptional oncology and a closely watched precedent for the miRNA therapeutic class.

CD30 bispecific antibodies and next-generation ADCs

Beyond brentuximab vedotin, the CD30 targeting space is evolving. CD30-directed bispecific T-cell engagers (BiTEs) and bispecific antibodies are in early clinical development, seeking to harness T-cell-mediated cytotoxicity against CD30-positive ALCL and PTCL cells. The mechanistic rationale differs from BV (which relies on ADC-mediated MMAE delivery): bispecific approaches redirect cytotoxic T cells or NK cells to CD30-expressing targets, potentially overcoming BV resistance mediated by MDR1-driven MMAE efflux or CD30 downregulation. Several IND-stage CD30 bispecific programs are active as of 2026, with Phase 1 data anticipated in ALCL and CD30-positive PTCL cohorts within the next 12–18 months.

CAR-T in T-cell lymphoma: the CD7 and CD4 frontiers

The fundamental challenge of CAR-T in T-cell malignancies — fratricide — has not prevented clinical development; it has redirected it toward engineered solutions. CD7 is expressed on approximately 95% of T-cell lymphomas and leukemias, making it the most broadly applicable T-cell target for CAR-T therapy. The fratricide problem (CD7 CAR-T cells killing each other via their own CD7 surface expression) is addressed by CRISPR/Cas9 knockout of the CD7 gene in the CAR-T product, generating cells that express the CD7-targeting CAR but no longer express the CD7 target on their surface.

Phase 1 data from CD7 CAR-T programs (NCT04689659 at Baylor; additional programs at the Chinese PLA General Hospital and University of Minnesota) have shown complete responses in heavily pre-treated T-cell lymphoma and leukemia patients, including some with prior alloSCT failure. These early signals have driven rapid expansion of CD7 CAR-T IND filings. Allogeneic (off-the-shelf) CD7 CAR-T programs address a second critical problem in autologous T-cell malignancy CAR-T manufacturing: using the patient's own malignant T cells as the starting material risks manufacturing a product contaminated with tumor cells. Allogeneic programs use healthy donor T cells with CRISPR deletion of both TCR (to prevent GvHD) and CD7 (to prevent fratricide).

CD4-directed CAR-T offers an alternative approach in CD4-positive PTCL subtypes (PTCL-NOS, AITL, ALCL). CD4 is more restricted in its expression than CD7, potentially reducing off-target toxicity, but CD4+ normal T-cell depletion creates significant immunosuppression. Phase 1 programs evaluating CD4 CAR-T in R/R CD4-positive T-cell lymphomas are actively enrolling as of 2026.

Who uses DataLookout for T-cell lymphoma monitoring

T-cell lymphoma is a high-complexity, multi-subtype landscape where competitive intelligence and trial monitoring require consistent, subtype-aware tracking. DataLookout serves three primary professional audiences:

• Pharma and biotech BD teams — Tracking competitor programs across CD30, CD7, CCR4, PI3K-delta/gamma, and HDAC inhibitor spaces; monitoring Phase 2 data readouts that signal NDA-readiness for potential licensing or acquisition targets; evaluating indication expansion opportunities (e.g., CD30 programs in ALCL extending to other CD30-positive subtypes)
• KOL hematologists and medical affairs — Identifying available trials for patients with relapsed PTCL or CTCL who have failed BV or mogamulizumab; monitoring change notifications for trials they are actively enrolling (protocol amendments, enrollment holds, primary completion date changes); staying current on HDAC inhibitor and IDH2 inhibitor combination data in AITL
• Healthcare investors and analysts — Monitoring Phase 2/3 enrollment velocity and trial completion timing for CAR-T, bispecific, and PI3K programs with potential NDA/BLA events; tracking which sponsors are adding PTCL cohorts to existing oncology programs (indicating pipeline optionality)

Related clinical trials and monitoring resources

T-cell lymphoma overlaps significantly with adjacent hematologic oncology pipelines. DataLookout monitors related areas including:

• Non-Hodgkin lymphoma clinical trials — broader NHL pipeline including B-cell and T-cell subtypes
• Hodgkin lymphoma clinical trials — shares brentuximab vedotin (CD30 ADC) and checkpoint immunotherapy landscape
• DLBCL clinical trials — aggressive B-cell lymphoma pipeline; CAR-T approvals and bispecific antibody programs inform T-cell lymphoma CAR-T strategy
• CLL clinical trials — BTK inhibitors and BCL-2 inhibitor combinations provide context for PI3K targeting in T-cell lymphoma; BTK and PI3K signaling node overlap in T-cell receptor pathway

Frequently asked questions

What are the main subtypes of peripheral T-cell lymphoma (PTCL)?

PTCL encompasses over 20 recognized subtypes under the WHO 2022 classification. The major categories are PTCL-NOS (~25–30%), AITL (~15–20%), ALK+ ALCL (~6–7%, favorable prognosis), ALK− ALCL (~6%), and cutaneous T-cell lymphomas (CTCL: mycosis fungoides and Sézary syndrome). NK/T-cell lymphoma (ENKTL) is biologically distinct and particularly prevalent in Asia. Each subtype has distinct genetic drivers, immunophenotype, and treatment implications — a single diagnostic category like "PTCL" is insufficient for trial monitoring; subtype-level tracking is necessary for accurate competitive intelligence.

What is the role of CD30 and CCR4 as biomarkers in T-cell lymphoma?

CD30 is expressed at high levels in ALCL (>90%) and variably in PTCL-NOS and AITL. CD30 positivity (IHC ≥10%) is the eligibility criterion for brentuximab vedotin + CHP in front-line PTCL per ECHELON-2 trial data. CCR4 is expressed in ~90% of CTCL/Sézary syndrome and ~30–40% of PTCL, and is the target of mogamulizumab (Poteligeo), approved in both settings. Routine IHC testing for CD30 and CCR4 at diagnosis is now standard practice, and both markers are key eligibility criteria in active clinical trials evaluating next-generation targeted agents in T-cell lymphoma.

Why is CAR-T cell therapy challenging in T-cell lymphomas?

CAR-T therapy in T-cell malignancies faces fratricide — when targeting a shared T-cell antigen (such as CD7 or CD3), the engineered CAR-T cells kill each other during manufacturing, eliminating the product before it can be infused. Solutions include CRISPR/Cas9 knockout of the target antigen in the CAR-T product (fratricide-resistant CD7 CAR-T), use of allogeneic donor-derived products (avoiding malignant T-cell contamination in autologous manufacturing), and protein expression blocker (PEBL) constructs. Phase 1 CD7 CAR-T programs have demonstrated early CRs in R/R T-cell lymphoma; this is one of the most active CAR-T development areas in hematologic oncology without an approved product.

How do HDAC inhibitors work and what is their current role in PTCL?

HDAC inhibitors (romidepsin, belinostat) work by preventing histone deacetylation, re-expressing silenced tumor suppressor genes and inducing apoptosis in T-cell lymphoma cells. Both are FDA-approved for relapsed/refractory PTCL with ORRs of ~25%. As monotherapy in relapsed disease, responses are not durable. The most promising current investigation is the combination of azacitidine + romidepsin in AITL, where the near-universal TET2/DNMT3A epigenetic mutation burden creates a rational target for dual HMA + HDAC inhibitor co-treatment; Phase 2 data show ORRs of 55–65% in AITL-enriched cohorts, substantially exceeding either agent alone.

What are the key molecular features of AITL relevant to clinical trials?

AITL is characterized by near-universal epigenetic mutations: TET2 (~75–80%), DNMT3A (~30%), RHOA G17V (~50–70%), and IDH2 R172 (~20–30%). IDH2 R172 mutations generate 2-hydroxyglutarate (2-HG), an oncometabolite that further suppresses TET2 — creating a "double-hit" epigenetic blockade unique to AITL. IDH2 R172 is actionable with enasidenib (Idhifa, FDA-approved in AML), which has shown ORRs of ~40–50% in IDH2-mutant PTCL/AITL cohorts in Phase 1/2 trials. AITL's SYK/PI3K signaling dependencies (driven by RHOA G17V activating VAV1 and downstream PI3K) make duvelisib (PI3K-delta/gamma) and cerdulatinib (SYK/JAK) rationally targeted agents with documented Phase 2 activity in this subtype.