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Safety Study of BTK Inhibitor, DTRMWXHS-12, Used Singly or in Combination, in CLL and B-cell Lymphomas

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ClinicalTrials.gov Identifier: NCT02900716
Recruitment Status : Recruiting
First Posted : September 14, 2016
Last Update Posted : November 28, 2018
Sponsor:
Information provided by (Responsible Party):
Zhejiang DTRM Biopharma

Brief Summary:

This study will evaluate the safety, antitumor activity and preliminary pharmacokinetics of an investigational drug product, DTRMWXHS-12, in patients with chronic lymphocytic leukemia or other B-cell lymphomas. DTRMWXHS-12 will be evaluated as a single agent, and in combination.

This study will be conducted in two parts: phase Ia and Ib. Both parts will explore escalating doses of DTRMWXHS-12. The phase Ia study will evaluate DTRMWXHS-12 monotherapy. The phase Ib study will evaluate DTRMWXHS-12 combinations.


Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia B-Cell Lymphoma Drug: DTRMWXHS-12 Drug: DTRM-505 Drug: DTRM-555 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ia/Ib Study of a Novel BTK Inhibitor, DTRMWXHS-12, and Combination Products, DTRM-505 and DTRM-555, in Patients With Chronic Lymphocytic Leukemia or Other B-cell Lymphomas
Study Start Date : September 2016
Estimated Primary Completion Date : December 2020


Arm Intervention/treatment
Experimental: Phase Ia
DTRMWXHS-12: oral capsules, daily x 21 days every 28 days
Drug: DTRMWXHS-12
DTRMWXHS-12

Experimental: Phase Ib, DTRM-505
DTRMWXHS-12 oral capsules and everolimus oral tablets: daily x 21 days every 28 days
Drug: DTRM-505
DTRMWXHS-12 and everolimus

Experimental: Phase Ib, DTRM-555

DTRMWXHS-12 and pomalidomide oral capsules, everolimus oral tablets:

daily x 21 days every 28 days

Drug: DTRM-555
DTRMWXHS-12 and everolimus and pomalidomide




Primary Outcome Measures :
  1. Number of patients with adverse events [ Time Frame: Starting from date of first dose up to 30 days after last dose ]
    Safety and tolerability


Secondary Outcome Measures :
  1. Plasma concentration over time [ Time Frame: Days 1-28 (first treatment cycle) ]
    Pharmacokinetics



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a diagnosis of chronic lymphocytic leukemia (CLL) or other B-cell neoplasms including small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL) and follicular B-cell non-Hodgkin's lymphoma (FL) who have no available approved therapies.
  • Age > 18 years.
  • Life expectancy greater than 12 weeks.
  • Patients must have an ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1.
  • Patients must provide written informed consent.
  • Ability to swallow and retain capsules.
  • Absence of uncontrolled intercurrent illnesses, including uncontrolled infections, cardiac conditions, or other organ dysfunctions.
  • 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 who can become pregnant, 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 previous chemotherapy, immunotherapy, radiotherapy or any other investigational therapy within 21 days or 5 half-lives for targeted therapies prior to this study entry.
  • Patients with active infections requiring intravenous (IV) antibiotic/antiviral therapy are not eligible for entry onto the study until resolution of the infection; patients on prophylactic antibiotics, antifungals or antivirals are acceptable
  • Pregnant or lactating individuals.
  • Impaired hepatic or renal function as demonstrated by any of the following laboratory values:

    1. AST or ALT > 2.5 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 1.5 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 (GFR) < 50 mL/min, as assessed using the standard methodology at the investigating center (i.e. Cockroft-Gault), or serum creatinine > 1.5 x ULN
  • INR > 1.5 or other evidence of impaired hepatic synthesis function.
  • Persisting (> 8 weeks) severe pancytopenia due to hematologic disorder or due to previous therapy rather than disease (ANC < 0.5 x 109/L or platelets < 30 x 109/L) - to be confirmed via bone marrow biopsy, as part of normal clinical care, prior to signing of consent.
  • Previous allogeneic bone marrow transplant are restricted, unless there is no evidence of acute or chronic graft versus host disease.
  • CNS involvement with malignancy.
  • 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 HIV, HBV or HCV infection.
  • Documented or known bleeding disorder.
  • Requirement for anticoagulation treatment that increases INR or aPTT above the normal range (low molecular weight heparin and heparin line flush allowed).
  • Patient is receiving any azole.
  • Patients with a significant cardiovascular disease or condition, including:

    • Myocardial infarction within 6 months of study entry
    • NYHA Class III or IV heart failure, or reduced LVEF <50%
    • Uncontrolled dysrhythmias or poorly controlled angina.
    • History of serious ventricular arrhythmia (VT or VF, ≥ 3 beats in a row) and/or risk factors (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
    • Baseline prolongation of QT/QTc interval (repeated demonstration of QTc ≥ 450 msec for men and 470 msec for women, or LVEF ≤ 40% by MUGA or ECHO).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02900716


Locations
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United States, Arizona
Mayo Clinic Recruiting
Phoenix, Arizona, United States, 85054
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Allison Rosenthal, MD         
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06510
Contact: Laura Leary, CCRC    203-737-8884    laura.leary@yale.edu   
Principal Investigator: Scott Huntington, MD         
United States, Florida
Mayo Clinic Recruiting
Jacksonville, Florida, United States, 32224
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Han Tun, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Offic    855-776-0015      
Principal Investigator: Wei Ding, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Danielle Brander, MD    919-684-8964    Danielle.brander@duke.edu   
Principal Investigator: Danielle Brander, MD         
United States, Pennsylvania
University of Pennsylvania Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Kaitlin Kennard, RN       kaitlin.kennard@uphs.upenn.edu   
Contact: Tanya Latorre, RN       Tanya.Latorre@uphs.upenn.edu   
Principal Investigator: Stephen J Schuster, MD         
Sponsors and Collaborators
Zhejiang DTRM Biopharma
Investigators
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Study Director: Wei He, Ph.D. Zhejiang DTRM Biopharma

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Responsible Party: Zhejiang DTRM Biopharma
ClinicalTrials.gov Identifier: NCT02900716     History of Changes
Other Study ID Numbers: D15-11094
First Posted: September 14, 2016    Key Record Dates
Last Update Posted: November 28, 2018
Last Verified: November 2018
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Lymphoma, Non-Hodgkin
Sirolimus
Everolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents