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

NCT04305444 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: DTRM-555_001
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 8

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.

Conditions

Relapsed Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Diffuse Large B Cell Lymphoma; Follicular Lymphoma; Richter's Transformation

Keywords

B-Cell Lymphoma; Diffuse Large B Cell Lymphoma; Everolimus; Follicular Lymphoma; Immunosuppressive Agents; Leukemia; B-Cell Leukemia; Chronic Lymphocytic Leukemia; Lymphatic Diseases; Lymphoma; Malignant Lymphoma; Non-Hodgkin Lymphoma; Lymphoproliferative Disorders; Neoplasms; Tyrosine Protein Kinase; Bruton's Tyrosine Kinase Inhibitor; Pomalidomide

Outcome Measures

Primary Outcomes (1)

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

  Response in lymphoma patients will be assessed according to Lugano 2014 criteria guidelines for response assessment of Hodgkin and non-Hodgkin lymphoma. Response in CLL patients will be assessed according to International Workshop on CLL (iwCLL) 2018 criteria for treatment of CLL.

  24 months

Secondary Outcomes (6)

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

  24 months

• Overall Response Rate (ORR) with DTRM-555 in the five disease-specific cohorts

  6, 12 and 24 months

• Plasma or blood concentration versus time profiles of DTRMWXHS-12, everolimus and pomalidomide will be evaluated to determine key pharmacokinetic parameters for the three drugs

  24 hours

• Plasma or blood concentration versus time profiles of DTRMWXHS-12, everolimus and pomalidomide will be evaluated to determine key pharmacokinetic parameters for the three drugs

  24 hours

• Plasma or blood concentration versus time profiles of DTRMWXHS-12, everolimus and pomalidomide will be evaluated to determine key pharmacokinetic parameters for the three drugs

  24 hours

Study Arms (1)

Disease-specific cohorts

EXPERIMENTAL

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

Drug: DTRM-555

Interventions

DTRM-555 DRUG

Oral once-daily administration

Also known as: DTRMWXHS-12, everolimus, pomalidomide

Disease-specific cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Received prior systemic anticancer treatment within the following time frames:
• Chemotherapy, immunotherapy, radiotherapy or any other investigational therapy within 21 days prior to starting study treatment.
• Targeted therapies within 5 biological half-lives prior to starting study treatment.
• 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 values:
• Aspartate transaminase (AST) or alanine transaminase (ALT) \> 2.5 x upper limit of normal (ULN); for patients with liver involvement, \> 5 x ULN
• 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)
• Alkaline phosphatase \> 2.5 x ULN
• 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.

Sponsors & Collaborators

• Zhejiang DTRM Biopharma: lead

Study Sites (8)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Yale - Smillow Cancer Hospital

New Haven, Connecticut, 06511, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

VA Medical Center - Memphis

Memphis, Tennessee, 38104-2127, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, B-Cell; Leukemia; Leukemia, B-Cell; Lymphatic Diseases; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoproliferative Disorders; Neoplasms

Interventions

DTRMWXHS-12; Everolimus; pomalidomide

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All patients, regardless of disease-specific cohort, will receive the same dose of DTRM-555. There are two stages to the study, and there is the potential for 120 patients in total (potentially 24 patients in each of the 5 cohorts) to participate in the study.

Study Record Dates

• First Submitted: March 6, 2020
• First Posted: March 12, 2020
• Study Start: April 24, 2020
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 8, 2025

Record last verified: 2025-01

Locations

US (8)