New Treatment for Systemic and Cutaneous T-cell Lymphomas: Antibody-drug Conjugate Brentuximab Vedotin

jruanBy Jia Ruan, MD

The peripheral T-cell lymphomas (PTCL) are uncommon lymphoid diseases that account for 5-10% of all non-Hodgkin lymphomas in adults in North America.  Compared to B-cell non-Hodgkin lymphomas, the PTCLs are generally aggressive and less responsive to current treatment options. Relapsed and refractory diseases are common.  Novel and target therapies are in much need to improve quality and duration of response.  At the 2012 American Society of Hematology (ASH) meeting in Atlanta, several research groups reported encouraging study results with the antibody-drug conjugate Brentuximab vedotin for T-cell lymphomas. Brentuximab vedotin (BV) is an anti-CD30 chimeric antibody conjugated by a protease-cleavable linker to the microtubule-disrupting agent monomethyl auristatin E. BV received accelerated FDA approval in 2011 for relapsed Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), 2 diseases that express abundant CD30.  Several new studies have looked at the treatment outcome of BV in patients with systemic or cutaneous T-cell lymphomas that express variable amount of CD30.

Studies in Systemic T-cell Lymphomas

Dr. Jacobsen from Dana Farber Cancer Institute reported an interim analysis of a phase II multicenter study which evaluated the antitumor activity of BV in patients with relapsed or refractory CD30-positive NHL. BV was administered at 1.8 mg/kg every 3 weeks by IV infusion. The study also explored the correlation between antitumor activity and quantitative CD30 expression.  Fifty-three patients with various CD30-positive NHLs have been enrolled, including 18 patients with mature T-/NK-cell lymphomas. Of the T-cell lymphoma patients enrolled, 9 have angioimmunoblastic T-cell lymphoma (AITL), 8 have PTCL-NOS, and 1 has cutaneous T-cell lymphoma.  The ORR was 27% (3/11) for mature T-/NK-cell NHLs.  Thus far, response was particularly noteworthy in in AITL where 3 of 5 patients (60%) have responded (2 CR, 1 PR).   Treatment-emergent adverse events were generally mild and moderate (grade 1/2), and expected including peripheral neuropathy and cytopenias, which was consistent with the safety profile of BV.  CD30 expression levels for patients with a CR or PR were widely variable and ranged from <1% to 90%.  Preliminary data seems to suggest that BV may be beneficial for patients with T-cell lymphomas that have low CD30 expression. Dr. Fanale from MD Anderson Cancer Center reported a phase I study with BV administered concurrently with multi-agent chemotherapy as frontline treatment of systemic ALCL and other CD30 positive T-cell lymphomas.  The study was Continue reading “New Treatment for Systemic and Cutaneous T-cell Lymphomas: Antibody-drug Conjugate Brentuximab Vedotin”

New Clinical Trial: Alisertib (MLN8237) or Investigator’s Choice for Relapsed/Refractory Peripheral T-Cell Lymphoma

A Phase 3, Randomized, Two-Arm, Open-Label, Multicenter, International Trial of Alisertib (MLN8237) or Investigator’s Choice (Selected Single Agent) in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma

Update: this study is closed to enrollment. 

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for people with relapsed or refractory Peripheral T-Cell Lymphoma (PTCL). The sponsor is Millennium Pharmaceuticals, and the principal investigator at Weill Cornell is Dr. Jia Ruan. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Study Details

The purpose of the study is to assess how well people with PTCL respond to treatment with the experimental drug Alisertib (also known as MLN8237) as compared to other PTCL treatments.

Study participants will be randomly assigned to receive Alisertib or one of the following drugs used to treat PTCL: pralatrexate, romidepsin or gemcitabine.

Alisertib has been developed to interfere with cell division, which is required for normal and cancer cell growth. By blocking an enzyme that cells need to reproduce, alistertib may slow the growth of cancer cells.

Key Eligibility

  • PTCL relapsed or refractory to at least 1 prior systemic, cytoxic therapy for PTCL
  • Must have received convential therapy (not experimental) as prior therapy

Treatment Plan

Study participants will be randomly assigned to one of two study arms:

  • Arm A: Alisertib tablet twice daily by mouth for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle for up to 32 cycles of treatment (2 years)
  • Arm B: Single-arm comparator. Participants will be assigned by the investigator to receive 1 of the following for up to 2 years:
    • Pralatrexate via infusion once weekly for 6 weeks in 7-week cycles. Cycles repeated every 7 weeks
    • Romidepsin via infusion on Days 1, 8 and 15 of a 28-day cycle. Cycles repeated every 28 days
    • Gemcitabine via infusion on Days 1, 8 and 15 of a 28-day cycle. Cycles repeated every 28 days

New Weill Cornell Study: Aurora Kinase A Inhibitor MLN8237 in Peripheral T-Cell non-Hodgkin Lymphoma

Update: this study is closed to enrollment. 
The Weill Cornell Lymphoma Program is now enrolling people in a new clinical trial for patients with peripheral T-cell lymphoma, a type of non-Hodgkin lymphoma that generally has a poor outcome with conventional chemotherapy.

The purpose of this study is to determine the effect of the experimental drug MLN8237 on patients with relapsed or refractory peripheral T-cell lymphoma. MLN8237 is an Aurora Kinase A inhibitor that has been developed to interfere with cell division, which is required for cancer to grow. It has been shown to have anti-cancer activity in laboratory studies as well as in patients who have non-Hodgkin lymphoma including peripheral T-cell lymphoma in earlier phase I/II studies.

MLN8237 is available as a tablet. Patients will take MLN8237 on Days 1-7, twice a day with 8 ounces of water. Patients will continue with this treatment every 3 weeks for up to a year as long as their disease does not get worse. Whether patients remain on study treatment or not, the study physician will follow their health status for a maximum of 2 years from study enrollment.

Key eligibility:

  • Relapsed/refractory peripheral T-cell non-Hodgkin lymphoma
  • Must have received at least one course of prior systemic therapy which may include chemotherapy, antibody therapy or immunotherapy
  • May have received prior radiation in combination with systemic therapy
  • Must not have received a previous allogeneic stem cell transplant or be within 90 days of autologous stem cell transplant
  • Detailed eligibility reviewed when you contact the study team

For more information about the study, call June Greenberg, RN at (212) 746-2651 or email June at jdg2002@med.cornell.edu.

The physician leading the study at Weill Cornell is Dr. Jia Ruan. Click here to read Dr. Ruan’s clinical and research profile.

Click here to view all current lymphoma clinical trials at Weill Cornell Medical College.

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