Testing the Addition of Duvelisib or CC-486 to the Usual Treatment for Peripheral T-Cell Lymphoma

Brief Title

Testing the Addition of Duvelisib or CC-486 to the Usual Treatment for Peripheral T-Cell Lymphoma

Official Title

A Randomized Phase II Study of CHO(E)P vs CC-486-CHO(E)P vs Duvelisib-CHO(E)P in Previously Untreated CD30 Negative Peripheral T-Cell Lymphomas

Brief Summary

      This phase II trial studies the effect of duvelisib or CC-486 and usual chemotherapy
      consisting of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone in
      treating patients with peripheral T-cell lymphoma. Duvelisib may stop the growth of cancer
      cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as
      CC-486, cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone, work in
      different ways to stop the growth of cancer cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. This trial may help find out if this
      approach is better or worse than the usual approach for treating peripheral T-cell lymphoma.
    

Detailed Description

      PRIMARY OBJECTIVE:

      I. To compare the complete remission (CR) rates by positron emission tomography
      (PET)/computed tomography (CT) following completion of treatment with
      duvelisib-cyclophosphamide (C) doxorubicin (H) vincristine (O) (etoposide [E]) prednisone (P)
      versus (vs) CHO(E)P and with oral azacitidine (CC-486)-CHO(E)P vs CHO(E)P in previously
      untreated peripheral T-cell lymphomas that have < 10% expression of CD30.

      SECONDARY OBJECTIVES:

      I. To determine the toxicity and tolerability of the treatment regimens. II. To determine the
      overall response rate (ORR), duration of response, progression free survival (PFS), event
      free survival (EFS), and overall survival (OS) of each treatment regimen.

      III. To determine whether designation of follicular helper T-cell phenotype is correlated
      with response to therapy, PFS, EFS, and OS.

      IV. To assess the toxicity profile of the experimental regimens in untreated CD30 negative
      peripheral T-cell lymphomas using Common Terminology Criteria for Adverse Events (CTCAE) and
      patient reported outcomes (PRO)-CTCAE.

      OUTLINE: Patients are randomized to 1 of 3 arms.

      ARM A: Patients receive cyclophosphamide intravenously (IV) on day 1, doxorubicin IV on day
      1, vincristine IV on day 1, etoposide IV on days 1-3 or etoposide IV on day 1 and orally (PO)
      once daily (QD) on days 2-3 for patients <=60 years old, and prednisone PO QD on days 1-5.
      Patients also receive duvelisib PO twice daily (BID) on days 1-21. Treatment repeats every 21
      days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

      ARM B: Patients receive cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV
      on day 1, etoposide IV on days 1-3 or etoposide IV on day 1 and orally (PO) once daily (QD)
      on days 2-3 for patients <=60 years old, and prednisone PO QD on days 1-5. Patients also
      receive CC-486 PO QD on days -6 to 0 of cycle -1 and days 8-21 of cycles 1-5. Treatment
      repeats every 21 days for up to 6 cycles in the absence of disease progression or
      unacceptable toxicity.

      ARM C: Patients receive cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV
      on day 1, etoposide IV on days 1-3 or etoposide IV on day 1 and orally (PO) once daily (QD)
      on days 2-3 for patients <=60 years old, and prednisone PO QD on days 1-5. Treatment repeats
      every 21 days for up to 6 cycles in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed at 6 weeks after cycle 6 day 1,
      then every 12 weeks for 2 years, then every 24 weeks until 5 years from end of treatment or
      until documented progression of lymphoma. After documented progression of lymphoma, patients
      are followed up every 6 months until 5 years from end of treatment.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Complete remission (CR) rate

Secondary Outcome

 Incidence of adverse events

Condition

Angioimmunoblastic T-cell Lymphoma

Intervention

Cyclophosphamide

Study Arms / Comparison Groups

 Arm A (duvelisib, CHO[E]P)
Description:  Patients receive cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, etoposide IV on day 1 or days 1-3 or PO QD on days 2-3 for patients =< 60 years old, and prednisone PO QD on days 1-5. Patients also receive duvelisib PO BID on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

170

Start Date

July 30, 2021

Completion Date

January 1, 2026

Primary Completion Date

June 30, 2025

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of peripheral T-cell lymphoma (PTCL) with < 10%
             CD30 expression by immunohistochemistry in the following subtypes (by local review):
             nodal T-cell lymphoma with T-follicular helper (TFH) phenotype (TFH-PTCL), follicular
             T-cell lymphoma, PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell
             lymphoma (AITL), enteropathy associated T-cell lymphoma, monomorphic epitheliotropic
             intestinal T-cell lymphoma

               -  Patients with expression of CD30 in >= 10% of the tumor (based on local
                  immunohistochemistry review) regardless of histology will not be permitted

               -  Patients with a diagnosis of other PTCL subtype histologies other than those
                  specified in the inclusion criteria are excluded including large cell
                  transformation of mycosis fungoides

               -  Patients will be stratified by presence or absence of TFH phenotype (i.e.
                  diagnosis of AITL, TFH-PTCL, follicular T-cell lymphoma) based on local review of
                  pathology. Determination of TFH phenotype can be defined by expression of two or
                  more of the following markers CD10, BCL6, CXCL13, ICOS, and PD1 by
                  immunohistochemistry

          -  Measurable disease as defined by the Lugano criteria

          -  No prior systemic therapy for lymphoma (excluding corticosteroids)

          -  Not pregnant and not nursing, because this study involves an investigational agent
             whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn
             are unknown. Therefore, for women of childbearing potential only, a negative urine or
             serum pregnancy test done =< 7 days prior to registration is required

          -  Age >= 18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Platelet count >= 75,000/mm^3 (>= 50,000/mm^3 if secondary to bone marrow involvement
             from lymphoma per investigator assessment; the first 12 patients on each arm of the
             study must have platelets >= 75,000/mm^3 regardless of bone marrow involvement)

          -  Absolute neutrophil count (ANC) >= 1,000/mm^3

          -  Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or
             alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 3.0 x
             upper limit of normal (ULN)

             * Except in subjects with documented liver involvement by lymphoma

          -  Calculated creatinine clearance >= 30 mL/min by Cockcroft-Gault formula

          -  Total bilirubin =< 2.0 x ULN

             * Except in cases of Gilbert's Syndrome or documented liver or pancreatic involvement
             by lymphoma

          -  Archival tissue must be available for submission

          -  Patients known to have HTLV 1/2 are excluded

          -  Patients with known central nervous system involvement are excluded

          -  No active viral infection with human immunodeficiency virus (HIV), hepatitis B, or
             hepatitis C. Those who are seropositive (e.g. hepatitis B core antibody [Ab] positive)
             are permitted if they are negative by polymerase chain reaction (PCR). Those who are
             seropositive for hepatitis B and are negative for hepatitis B virus (HBV)
             deoxyribonucleic acid (DNA) by PCR must receive concomitant hepatitis B directed
             antiviral therapy. Those who have hepatitis C Ab positivity who have completed
             curative therapy for hepatitis C with negative hepatitis C PCR are eligible

          -  Patients with history of HIV are eligible if they have an undetectable viral load for
             at least 6 months

          -  No active uncontrolled systemic fungal, bacterial or viral infection (defined as
             ongoing signs/symptoms related to the infection without improvement despite
             appropriate antibiotics, antiviral therapy and/or other treatment). Patients with
             Epstein-Barr virus (EBV) viremia related to their lymphoma are permitted

          -  No concurrent malignancy requiring active therapy within the last 3 years with the
             exception of basal cell carcinoma limited to the skin, squamous cell carcinoma limited
             to the skin, carcinoma in situ of the cervix, breast or localized prostate cancer.
             Adjuvant hormonal therapy for cancer previously treated for curative intent is
             permitted

          -  Patients must have documented left ventricular ejection fraction of >= 45%

          -  No significant active cardiac disease within the previous 6 months including:

               -  New York Heart Association (NYHA) class III or IV congestive heart failure

               -  Unstable angina or angina requiring surgical or medical intervention; and/or

               -  Myocardial infarction

          -  No contraindication to any drug in the chemotherapy regimen, including neuropathy >=
             grade 2

          -  Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this
             study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days
             prior to registration on the study. Chronic concomitant treatment with strong CYP3A4
             inducers is not allowed. Patients must discontinue the drug 14 days prior to the start
             of study treatment
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Neha Mehta-Shah, MD, MSCI, 314-747-7510, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04803201

Organization ID

A051902

Secondary IDs

NCI-2021-01380

Responsible Party

Sponsor

Study Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Neha Mehta-Shah, MD, MSCI, Study Chair, Washington University School of Medicine


Verification Date

September 2021