Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin’s Lymphomas

Learn more about:
Related Clinical Trial
A Study of PRT2527 in Participants With Relapsed/Refractory Hematologic Malignancies Lisocabtagene Maraleucel, Nivolumab and Ibrutinib for the Treatment of Richter’s Transformation Acalabrutinib, Venetoclax and Durvalumab for the Treatment of Richter Transformation From Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Safety & Efficacy Study of Epcoritamab in Subjects With R/R Chronic Lymphocytic Leukemia and Richter’s Syndrome ALX148, Rituximab and Lenalidomide for the Treatment of Indolent and Aggressive B-cell Non-Hodgkin Lymphoma R-EPOCH in Combination With Ibrutinib for Patients With Classical RT of CLL Phase 1 Study VIP152 in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia or Richter Syndrome A Study to Evaluate the Efficacy and Safety of Obinutuzumab, Ibrutinib, and Venetoclax in Patients With Richter’s Syndrome; Study of Cosibelimab in Subjects With Relapsed or Refractory Lymphoma CD19-Directed CAR-T Cell Therapy for the Treatment of Relapsed/Refractory B Cell Malignancies Study of TG-1801 Alone or in Combination With Ublituximab in Subjects With B-Cell Lymphoma or Chronic Lymphocytic Leukemia Study of Oral Administration of LP-118 in Patients With Relapsed or Refractory NHL, RT, MM, T-PLL, Acute Leukemia (AML, ALL), MDS, MDS/MPN, and MF Ipilimumab, Ibrutinib, and Nivolumab for the Treatment of Chronic Lymphocytic Leukemia and Richter Transformation Polatuzumab Vedotin in Combination With Chemotherapy in Subjects With Richter’s Transformation Autologous Stem Cell Transplant Followed by Polatuzumab Vedotin in Patients With B-cell Non-Hodgkin and Hodgkin Lymphoma Venetoclax in Combination With Ublituximab and Umbralisib (TGR-1202) in Patients With Relapsed or Refractory CLL/SLL Ex Vivo-activated Autologous Lymph Node Lymphocytes in Treating Patients With Chronic Lymphocytic Leukemia Allogeneic Stem Cell Transplant for CLL Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin’s Lymphomas Atezolizumab, Gemcitabine, Oxaliplatin, and Rituximab in Treating Patients With Relapsed or Refractory Transformed Diffuse Large B-Cell Lymphoma Atezolizumab, Obinutuzumab, and Venetoclax in Treating Patients With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Relapsed or Refractory Richter Syndrome Duvelisib and Nivolumab in Treating Patients With Richter Syndrome or Transformed Follicular Lymphoma Sotrastaurin Acetate in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, Prolymphocytic Leukemia, or Richter’s Transformation Registry of the German CLL Study Group Nivolumab and Ibrutinib in Treating Patients With Relapsed, Refractory, or High-Risk Untreated Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Richter Transformation ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (Btk) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia A Study of Acalabrutinib and Vistusertib in Subjects With Relapsed/Refractory B-cell Malignancies Study of Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone (CHOP) With Ofatumumab in Patients With Richter’s Syndrome PNT2258 for Treatment of Patients With Richter’s Transformation (Brighton) Study of Immunotherapy in Combination With Ublituximab and Umbralisib in Patients With Relapsed-refractory CLL or Richter’s Transformation Efficacy and Safety of Zanubrutinib Plus Tislelizumab for Treatment of Patients With Richter Transformation BLINAtumomab After R-CHOP Debulking Therapy for Patients With Richter Transformation Oxaliplatin, Fludarabine, Cytarabine, and Rituximab in Patients With Richter’s Transformation and Leukemias Obinutuzumab Containing Conditioning Regimen for Patients With Poor Risk CLL or Richter`s Transformation Requiring Allogeneic Stem Cell Transplantation Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma or Relapsed or Refractory Richter Syndrome (MK-3475-170/KEYNOTE-170) Duvelisib and Venetoclax in Relapsed or Refractory CLL or SLL or RS Study of Blinatumomab in Richter Transformation Genomic and Proteomic Study of Richter Syndrome (CGPSR) CRC043: A Phase II Study of Venetoclax in Combination With Dose-adjusted EPOCH-R for Patients With Richter’s Syndrome Study of Ibrutinib & Obinutuzumab With/Without CHOP for Richter’s Transformation or Richter’s Syndrome Patients Obinutuzumab, High Dose Methylprednisolone (HDMP), and Lenalidomide for the Treatment of Patients With Richter’s Syndrome A Trial of CHOP-R Therapy, With or Without Acalabrutinib, in Patients With Newly Diagnosed Richter’s Syndrome Selinexor in Initial or Refractory and/or Relapsed Richter’s Transformation

Brief Title

Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin's Lymphomas

Official Title

Phase II Expansion Cohorts Studies of a Novel Triple Combination Therapy, DTRM-555, in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia or Relapsed/Refractory Non-Hodgkin's Lymphomas

Brief Summary

      Targeted drug therapies have greatly improved outcomes for patients with relapsed or
      refractory (R/R) chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma. However,
      single drug therapies have limitations, therefore, the current study is evaluating a novel
      oral combination of targeted drugs as a way of overcoming these limitations. This study will
      determine the efficacy of the triple combination therapy, DTRM-555, in patients with R/R CLL
      or R/R non-Hodgkin's lymphoma.

Detailed Description

      This study is being conducted in three parts: Phase Ia, Phase Ib and Phase II,
      disease-specific expansion cohorts. Phase Ia explored escalating doses of a monotherapy of a
      novel Bruton's Tyrosine Kinase (BTK) inhibitor, DTRMWXHS-12. Phase Ib explored two
      combination therapies, DTRM-505 (DTRMWXHS-12 and everolimus) and DTRM-555 (DTRMWXHS-12,
      everolimus and pomalidomide).

      The current Phase II study will further examine the investigational triple combination
      treatment, DTRM-555 for efficacy and safety. The study is being conducted in five
      disease-specific cohorts: Activated B-Cell (ABC) Diffuse Large B-Cell Lymphoma, Germinal
      Center B-Cell (GCB) Diffuse Large B-Cell Lymphoma, Richter's Transformation, transformed
      Follicular Lymphoma, and relapsed or refractory Chronic Lymphocytic Leukemia.

      The Primary Objective of the Phase II study is to determine the efficacy of the triple
      combination therapy, DTRM-555, in the five disease-specific cohorts. The Secondary Objectives
      are (1) to determine the safety of DTRM-555 in the cohorts and (2) to obtain the
      pharmacokinetics of DTRM-555 (i.e., DTRMWXHS-12, everolimus and pomalidomide).

Study Phase

Phase 2

Study Type


Primary Outcome

Complete Responses (CR) and Partial Responses (PR) with DTRM-555 in the five disease-specific cohorts

Secondary Outcome

 Treatment-Emergent Adverse Events (AEs) in the five disease-specific cohorts


Relapsed Chronic Lymphocytic Leukemia



Study Arms / Comparison Groups

 Disease-specific cohorts
Description:  Participants will be administered the oral triple-combination therapy, DTRM-555 (comprised of 200mg of DTRMWXHS-12, 5mg of everolimus and 2mg of pomalidomide), once-daily for 21 consecutive days every 28 days


* 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


Estimated Enrollment


Start Date

April 24, 2020

Completion Date

March 2024

Primary Completion Date

March 2024

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must provide written informed consent.

          -  Patients with a diagnosis of R/R CLL or other B-cell neoplasms (i.e., ABC DLBCL, GCB
             DLBCL, Richter's transformation and tFL) who have no available approved therapies, or
             patients with a diagnosis of non-Hodgkin's lymphoma, which has relapsed and/or is
             refractory to standard therapy.

             a. Patients with R/R CLL must have been exposed to Bruton's tyrosine kinase (BTK) or
             B-Cell CLL/Lymphoma 2 (BCL2) inhibitor-based therapy in prior lines of therapy but
             must not have known Cys481 resistance mutation prior to study enrollment.

          -  Age ≥ 18 years.

          -  Life expectancy greater than 12 weeks.

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0 or 1.

          -  Ability to swallow and retain capsules and/or tablets.

          -  Absence of uncontrolled intercurrent illnesses, including uncontrolled infections,
             cardiac conditions, or other organ dysfunctions.

          -  If the patient consents to an optional tumor biopsy, he/she must have a tumor that can
             be safely biopsied and undergo a baseline tumor biopsy procedure, or be willing to
             provide available archival tissue collected within 6 months of signing the Informed
             Consent Form (ICF), and one post-Cycle 1 treatment biopsy.

          -  Patients must have at least one target lesion according to Lugano Classification.
             Patients with R/R CLL are exempt from this requirement.

          -  Women of child-bearing potential must have a negative serum or urine pregnancy test.

          -  Women of child-bearing potential must agree to use 2 reliable methods of contraception
             beginning 4 weeks prior to the initiation of treatment, during therapy, and for at
             least 4 weeks after the last drug administration.

          -  Men must agree to use a latex or synthetic condom during sexual contact with a
             pregnant female or a female of child-bearing potential, for the duration of the study
             and for at least 4 weeks after the last drug administration, even if they have
             undergone a successful vasectomy.

        Exclusion Criteria:

          -  Received prior systemic anticancer treatment within the following time frames:

               1. Chemotherapy, immunotherapy, radiotherapy or any other investigational therapy
                  within 21 days prior to starting study treatment.

               2. Targeted therapies within 5 biological half-lives prior to starting study

          -  Patients with active infections requiring therapy are not eligible for entry into the
             study until resolution of the infection; however, patients on prophylactic
             antibiotics, antifungals or antivirals are eligible for entry into the study.

          -  Pregnant or lactating individuals.

          -  Impaired hepatic or renal function as demonstrated by any of the following laboratory

               1. Aspartate transaminase (AST) or alanine transaminase (ALT) > 2.5 x upper limit of
                  normal (ULN); for patients with liver involvement, > 5 x ULN

               2. Total bilirubin > 1.5 x ULN (Patients with a history of Gilbert's syndrome may
                  participate if total bilirubin is less than or equal to 3 x ULN and the AST/ALT
                  and alkaline phosphatase meet the protocol-specified levels for eligibility)

               3. Alkaline phosphatase > 2.5 x ULN

               4. Glomerular filtration rate < 50 mL/min, as assessed using the standard
                  methodology at the investigating center (i.e., Cockcroft-Gault), or serum
                  creatinine > 1.5 x ULN

          -  International normalized ratio (INR) > 1.5 or other evidence of impaired hepatic
             synthesis function.

          -  Absolute neutrophil count < 1.0 x 109/L or platelets < 100 x 109/L, unless due to
             disease-related bone marrow impairment as confirmed by bone marrow biopsy during
             screening or due to standard of care treatment within 2 months prior to signing of
             informed consent. Patients with bone marrow impairment will be excluded if their
             absolute neutrophil count (ANC) is < 0.5 x 109/L and platelets < 50 x 109/L.

          -  Previous allogeneic bone marrow transplant is restricted, unless transplant was
             greater than 3 months prior and there is no evidence of acute or chronic graft versus
             host disease.

          -  Central nervous system involvement with malignancy.

          -  Patients who have poorly controlled diabetes mellitus or whose glucose values cannot
             be controlled with medical treatment.

          -  Current malignancies of another type, with the exception of adequately treated in situ
             cervical cancer and basal cell skin cancer, squamous cell carcinoma of the skin or
             other malignancies with no evidence of disease for 2 years or more.

          -  Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus
             (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core
             antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative
             polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive
             will be excluded.

          -  Documented or known bleeding disorder.

          -  Requirement for anticoagulation treatment that increases INR or activated partial
             thromboplastin time above the normal range (low molecular weight heparin and heparin
             line flush allowed).

          -  Patients requiring the use of strong CYP3A4, CYP1A2, or P-gp inhibitors.

          -  Patients with a significant cardiovascular disease or condition, including:

               1. myocardial infarction within 6 months of study entry,

               2. New York Heart Association Class III or IV heart failure,

               3. uncontrolled dysrhythmias or poorly controlled angina,

               4. history of serious ventricular arrhythmia (ventricular fibrillation or
                  ventricular tachycardia, ≥ 3 beats in a row) and/or risk factors (e.g., heart
                  failure, hypokalemia, or family history of Long QT Syndrome),

               5. baseline prolongation of QT/QTc interval (repeated demonstration of corrected QT
                  interval (QTc) ≥ 450 msec for men and 470 msec for women), and

               6. left ventricular ejection fraction (LVEF) < 45% by multiple gated acquisition
                  (MUGA) and /or echocardiogram (ECHO).




18 Years - N/A

Accepts Healthy Volunteers



, (215) 337-3168, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Zhejiang DTRM Biopharma

Study Sponsor

, , 

Verification Date

April 2022