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B-Cell MalignanciesPhase 1NCT05275504

Study to Evaluate the Safety and Tolerability of TT-01488 in Patients With B-Cell Malignancies

A Phase 1 study testing TT-01488 in people with B-Cell Malignancies, run by TransThera Sciences (Nanjing), Inc. at 2 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a first-in-human (FIH), multicenter, open-label Phase I dose escalation study to evaluate the safety and preliminary efficacy of the TT-01488 tablet, a non-covalent reversible BTK inhibitor, for the treatment of adult patients with B-cell malignancies. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
B-Cell Malignancies
What is being tested?
TT-01488
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
2 sitesUnited States
Study dates
Jun 2022to Apr 2023
Phase
Phase 1
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

  • Men and women ≥ 18 years of age with histologically or cytologically confirmed R/R B-NHL, including but not limited to chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL), Waldenström macroglobulinemia (WM), follicular lymphoma (FL), marginal zone lymphoma (MZL), diffuse large-b-cell lymphomas (DLBCL), and transformed lymphoma who failed or are intolerant to ≥ 1 prior standard of care regimens.
  • Notes:
  • Patients with prior treatment of BTK inhibitors are eligible
  • Patients with low grade lymphoma must be progressing and requiring treatment:
  • Patients with CLL must have disease requiring treatment as specified in 2018 IWCLL Guidelines (Appendix 5)
  • Patients with B-cell NHL must have measurable disease per 2014 Lugano Classification (Appendix 6)
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  • Patients with WM must have minimum serum immunoglobulin M (IgM) level of ≥ 2 times the upper limit of normal (ULN)
  • Body weight ≥ 40 kg
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Adequate organ function, defined by the following laboratory parameters:
  • Hematologic:
  • Absolute neutrophil count (ANC) ≥ 750/ul, unless due to bone marrow involvement due to disease
  • Platelets ≥ 50,000/ul without transfusion within 7 days
  • Hemoglobin ≥ 80 mg/dl without transfusion within 7 days
  • Coagulation:
  • Prothrombin time (PT) ≤ 1.5 × ULN
  • Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
  • Renal function:
  • o Creatinine clearance ≥ 60 mL/min estimated glomerular filtration rate based on Cockcroft-Gault formula or 24-hour urine collection
  • Liver function:
  • Total bilirubin ≤ 1.5 × ULN (unless due to Gilbert's disease)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × ULN unless disease-related
  • Agreement to use contraception during the study and until at least 6 months after the last dose of study drug if sexually active and able to bear children
  • Willing and able to participate in all required evaluations and procedures in the study protocol including swallowing tablets without difficulty
  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations)

Who cannot join

  • Women who are pregnant or lactating
  • Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years or which will not limit survival to < 2 years (Note: these cases must be discussed with the Medical Monitor and/or Investigator)
  • A life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of TT-01488, or put the study outcomes at undue risk
  • Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or significant screening ECG abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, and corrected QT interval using Fridericia's Formula (QTcF) > 470 msec, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
  • Any immunotherapy, , radiotherapy (limited-field radiation for palliation within 7 days), or experimental therapy within 4 weeks, or 5-half lives for chemotherapy and small molecule agents (whichever is shorter), before first dose of study drug (corticosteroids for disease-related symptoms allowed but require 1-week washout before study drug administration)
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  • History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T-cell (CAR-T) therapy within the past 60 days or with any of the following:
  • Active graft versus host disease (GvHD);
  • Cytopenias from incomplete blood cell count recovery post-transplant;
  • Need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity > Grade 1 from CAR-T therapy;
  • Ongoing immunosuppressive therapy
  • Concomitant use of prohibited medications(Section 6.4.2), including:
  • Therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants
  • Medications with known risk to cause QT prolongation or Torsades de pointes
  • Strong CYP3A inhibitors and inducers (must be discontinued for at least 14 days or 5 half-lives, whichever is longer, before study treatment)
  • Proton pump inhibitors, histamine-2 blockers (H2 blockers), and locally acting antacids (Note: For patients who are dependent upon this class of medications, patients may be considered after consulting with the study investigator and Sponsor. See Section 6.4.2 for more details).
  • Central nervous system involvement by lymphoma
  • Grade ≥ 2 toxicity (other than alopecia) continuing from prior anticancer therapy, including radiation
  • Known history of Human Immunodeficiency Virus (HIV) or active infection with Cytomegalovirus (CMV), Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV), or any uncontrolled active systemic infection
  • Major surgery within 4 weeks before first dose of study drug

Trial locations and contacts

2 sites in 1 country.

Caixia Sun, PhD contact

025-58216298

clinicaltrial@transtherabio.com

United States2 sites, 2 recruiting

  • Gabrail Cancer Center

    Canton, Ohio, 44718

    Recruiting

  • The University of Texas MD Anderson Cancer Center (MDACC)

    Houston, Texas, 77030

    Not yet recruiting

Other trials in United States

About this study

Official title: A Phase I, First-In-Human, Multicenter, Open Label, and Dose-Escalation Study of TT-01488, Administered Orally in Adult Patients With B-Cell Malignancies

This is a first-in-human (FIH), multicenter, open-label Phase I dose escalation study to evaluate the safety and preliminary efficacy of the TT-01488 tablet, a non-covalent reversible BTK inhibitor, for the treatment of adult patients with B-cell malignancies.

Read the detailed description

The study will consist of two parts, dose escalation and dose expansion. A modified 3+3 design will be used to guide the dose escalation and the determination of the dose recommended for dose expansion (DRDE). A sentinel cohort comprising of one subject will be enrolled at a starting dose of 50 mg q.d. Subsequently, patients will be enrolled according to the standard 3+3 dose escalation design to determine the DRDE. Once the DRDE has been selected, TT-01488 of DRDE will be further tested in the dose expansion cohort to verify the safety and preliminary efficacy as observed in the dose escalation cohorts. A recommended Phase II dose (RP2D) may be determined based on the totality of safety, pharmacokinetics, and efficacy data from the dose escalation cohorts and dose expansion cohort.

Being tested
TT-01488
Keywords
B-Cell Malignancies, Non-Hodgkin's Lymphomas (NHL), BTK inhibitor, C481S mutation

What participants receive

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

  • TT-01488Drug

    TT-01488 tablet will be administered orally once daily per protocol defined schedule.

Study groups in NCT05275504
Study groupRoleWhat they receive
Dose Escalation for TT-01488ExperimentalTT-01488 tablets will be administered once daily in a 28-day cycle in increasing strength in order to determine the recommended dose for dose expansion.
Receives: Drug: TT-01488
Dose Expansion for TT-01488ExperimentalTT-01488 tablets will be administered once daily in 28-day cycles to verify the safety and preliminary efficacy as observed in the dose escalation cohorts.
Receives: Drug: TT-01488

What is being measured

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

  1. Dose-Limiting Toxicity (DLT) of TT-01488

    Safety and tolerability of TT-01488 as a single agent

    Measured: Up to 28 days after first dose

  2. Dose recommend for dose expansion (DRDE)

    Safety and tolerability of TT-01488 as a single agent

    Measured: 1 - 1.5 years

  3. Maximum Tolerated Dose (MTD), if reached, of TT-01488

    Safety and tolerability of TT-01488 as a single agent

    Measured: Up to 28 days after first dose

Secondary outcomes (13)

  1. Number of participants with treatment-related adverse events (AEs)

    Safety and tolerability of TT-01488 as a single agent. AEs will be assessed per CTCAE v5.0 and may include, but is not limited to, clinically abnormal laboratory tests, physical exams, vital signs, electrocardiograms, and ECOG performance status.

    Measured: 1 - 1.5 years

  2. Objective Response Rate (ORR)

    Preliminary efficacy profile of TT-01488 as a single agent

    Measured: 1 - 1.5 years

  3. Disease Control Rate (DCR)

    Preliminary efficacy profile of TT-01488 as a single agent

    Measured: 1 - 1.5 years

  4. Duration of Response (DOR)

    Preliminary efficacy profile of TT-01488 as a single agent

    Measured: 1 - 1.5 years

  5. Progression free survival (PFS)

    Preliminary efficacy profile of TT-01488 as a single agent

    Measured: 1 - 1.5 years

  6. Overall survival (OS)

    Preliminary efficacy profile of TT-01488 as a single agent

    Measured: 1 - 1.5 years

  7. Recommended Phase 2 dose (RP2D)

    Safety and tolerability of TT-01488 as a single agent

    Measured: 1 - 1.5 years

  8. Area under the concentration time curve (AUC 0-last)

    Pharmacokinetic (PK) profile of TT-01488 as a single agent

    Measured: 1 - 1.5 years

  9. Maximum plasma concentration (Cmax)

    Pharmacokinetic (PK) profile of TT-01488 as a single agent

    Measured: 1 - 1.5 years

  10. Time to Maximum Plasma Concentration (Tmax)

    Pharmacokinetic (PK) profile of TT-01488 as a single agent

    Measured: 1 - 1.5 years

  11. Half-life (T1/2)

    Pharmacokinetic (PK) profile of TT-01488 as a single agent

    Measured: 1 - 1.5 years

  12. Mean Residence Time (MRT)

    Pharmacokinetic (PK) profile of TT-01488 as a single agent

    Measured: 1 - 1.5 years

  13. Volume of Distribution (Vd)

    Pharmacokinetic (PK) profile of TT-01488 as a single agent

    Measured: 1 - 1.5 years

Timeline

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

  1. First posted11 Mar 2022
  2. Study startJun 2022 (estimated)
  3. Primary completionSep 2022 (estimated)
  4. Study completionApr 2023 (estimated)

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
37 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05275504
Sponsor's protocol ID
TT01488US01
Status last verified
Jun 2022
First submitted
21 Feb 2022
Last updated
9 Jun 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TT-01488 in people with B-Cell Malignancies, run by TransThera Sciences (Nanjing), Inc. at 2 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 25 inclusion and 20 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: status not confirmed, as of the sponsor's last update on 9 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

Results are not available in the source record.

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

Contact Caixia Sun, PhD (025-58216298, clinicaltrial@transtherabio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-Limiting Toxicity (DLT) of TT-01488 (time frame: Up to 28 days after first dose). The study lists 3 primary outcomes in all. 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 NCT05275504.

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 9 Jun 2022.

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