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Relapsed Chronic Lymphocytic LeukemiaPhase 2NCT04305444

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

A Phase 2 study testing DTRM-555 in people with Relapsed Chronic Lymphocytic Leukemia and Refractory Chronic Lymphocytic Leukemia, run by Zhejiang DTRM Biopharma at 8 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
DTRM-555
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
8 sitesUnited States
Study dates
24 Apr 2020to 31 Dec 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
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  • 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.

Who cannot join

  • 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:
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  • 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.
  • 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:
  • myocardial infarction within 6 months of study entry,
  • New York Heart Association Class III or IV heart failure,
  • uncontrolled dysrhythmias or poorly controlled angina,
  • 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),
  • baseline prolongation of QT/QTc interval (repeated demonstration of corrected QT interval (QTc) ≥ 450 msec for men and 470 msec for women), and
  • left ventricular ejection fraction (LVEF) < 45% by multiple gated acquisition (MUGA) and /or echocardiogram (ECHO).

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Duke Cancer Institute

    Durham, North Carolina, 27710

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • VA Medical Center - Memphis

    Memphis, Tennessee, 38104-2127

  • Yale - Smillow Cancer Hospital

    New Haven, Connecticut, 06511

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Pennsylvania Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic

    Phoenix, Arizona, 85054

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

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

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.

Read the 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).

Being tested
DTRM-555
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
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, B-Cell, Leukemia, Leukemia, B-Cell, Lymphatic Diseases, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DTRM-555Drug

    Also called DTRMWXHS-12, everolimus, pomalidomide

    Oral once-daily administration

Study groups in NCT04305444
Study groupRoleWhat they receive
Disease-specific cohortsExperimentalParticipants 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
Receives: Drug: DTRM-555

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 24 months

Secondary outcomes (6)

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

    Percentage of participants with Treatment-Emergent Adverse Events (AEs)

    Measured: 24 months

  2. Overall Response Rate (ORR) 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 iwCLL 2018 criteria for treatment of CLL.

    Measured: 6, 12 and 24 months

  3. 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

    Plasma or blood concentration versus time profiles of DTRMWXHS-12, everolimus and pomalidomide will be evaluated to determine Area Under the Curves (AUC)

    Measured: 24 hours

  4. 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

    Plasma or blood concentration versus time profiles of DTRMWXHS-12, everolimus and pomalidomide will be evaluated to determine Maximum Observed Plasma or Blood Concentrations (Cmax)

    Measured: 24 hours

  5. 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

    Plasma or blood concentration versus time profiles of DTRMWXHS-12, everolimus and pomalidomide will be evaluated to determine the Times to Reach Cmax (tmax)

    Measured: 24 hours

  6. 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

    Plasma or blood concentration versus time profiles of DTRMWXHS-12, everolimus and pomalidomide will be evaluated to determine Elimination Half-Lives (t1/2)

    Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2020
  2. Study start24 Apr 2020
  3. Primary completion31 Dec 2024
  4. Study completion31 Dec 2024

Why it stopped: Despite the efforts of our dedicated team and initial progress, we were unable to secure the necessary financial resources to continue the study. We appreciate the support and participation of all involved.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04305444
Sponsor's protocol ID
DTRM-555_001
Status last verified
Jan 2025
First submitted
6 Mar 2020
Last updated
8 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DTRM-555 in people with Relapsed Chronic Lymphocytic Leukemia and Refractory Chronic Lymphocytic Leukemia, run by Zhejiang DTRM Biopharma at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Despite the efforts of our dedicated team and initial progress, we were unable to secure the necessary financial resources to continue the study. We appreciate the support and participation of all involved.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Responses (CR) and Partial Responses (PR) with DTRM-555 in the five disease-specific cohorts (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04305444.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2025.

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