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

NCT ID: NCT02900716

Last Updated: 2020-11-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-30

Study Completion Date

2020-11-23

Brief Summary

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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.

Detailed Description

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Conditions

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Chronic Lymphocytic Leukemia B-Cell Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase Ia

DTRMWXHS-12: oral capsules, daily x 21 days every 28 days

Group Type EXPERIMENTAL

DTRMWXHS-12

Intervention Type DRUG

DTRMWXHS-12

Phase Ib, DTRM-505

DTRMWXHS-12 oral capsules and everolimus oral tablets: daily x 21 days every 28 days

Group Type EXPERIMENTAL

DTRM-505

Intervention Type DRUG

DTRMWXHS-12 and everolimus

Phase Ib, DTRM-555

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

daily x 21 days every 28 days

Group Type EXPERIMENTAL

DTRM-555

Intervention Type DRUG

DTRMWXHS-12 and everolimus and pomalidomide

Interventions

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DTRMWXHS-12

DTRMWXHS-12

Intervention Type DRUG

DTRM-505

DTRMWXHS-12 and everolimus

Intervention Type DRUG

DTRM-555

DTRMWXHS-12 and everolimus and pomalidomide

Intervention Type DRUG

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Zhejiang DTRM Biopharma

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Wei He, Ph.D.

Role: STUDY_DIRECTOR

Zhejiang DTRM Biopharma

Locations

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Mayo Clinic

Phoenix, Arizona, United States

Site Status

Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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D15-11094

Identifier Type: -

Identifier Source: org_study_id