ADAM17 Inhibitor/ Rituximab After Auto HCT for DLBCL

Study of the ADAM17 Inhibitor INCB7839 Combined With Rituximab After Autologous Hematopoietic Cell Transplantation (HCT) For Patients With Diffuse Large B Cell Non-Hodgkin Lymphoma (DLBCL)

NCT02141451•Masonic Cancer Center, University of Minnesota

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Summary

This is a single institution phase I/II study using an ADAM17 inhibitor (INCB7839) with rituximab as consolidation therapy after an autologous hematopoietic cell transplant (HCT) for patients with diffuse large B cell lymphoma (DLBCL). The study consists of two phases. The dose finding phase is a modified version of a phase I trial and the extended phase is a modified version of a phase II trial.

Detailed Description

The primary goal of the dose finding phase is to determine the maximum tolerated dose (MTD) of INCB7839. Up to three dose levels will be tested (100 mg bid, 200 mg bid, and 300 mg bid). As the 300 mg bid has been proven safe in the non-transplant setting, dose escalation follows a Fast-Track Design with 1 patient enrolled per dose level unless a grade 2 or greater treatment emergent event occurs within the 1st 14 days of INCB7839. At that point, dose escalation converts to a standard 3+3 design and two additional patients are enrolled at the current dose level. If dose level 3 is completed without dose limiting toxicity (DLT) in the 1st 3 patients, an additional 3 patients will be enrolled at this level (without the staggering required by the DLT rules) prior to moving to the phase II component. Once the phase I dose escalation is completed, an additional 12 patients will be enrolled at the MTD (or dose level 3, if no DLT) to obtain a more detailed toxicity profile as well as a preliminary estimate of progression free survival at 6 months post-transplant.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients 18 years or older who have undergone an autologous HCT for the treatment of DLBCL and are in a complete remission (CR), partial remission (PR) or have stable disease (SD) at the day 28 post-transplant reassessment
•Karnofsky Score of ≥ 70% (appendix II)
•Able to start the protocol therapy (1st dose of rituximab) between day 28-75 post-transplant
•Adequate organ function defined as:
•* Hematologic: platelets ≥ 50,000 x 109/L; ANC ≥ 1000 x 109/L unsupported by G-CSF or GM-CSF for 3 days
•* Renal: creatinine \< 1.5 mg/dl or glomerular filtration rate \> 50 ml/min
•* Pulmonary: clinically no evidence of pulmonary disease
•* Cardiac: no symptoms of uncontrolled cardiac disease
•If post-transplant consolidation radiation therapy is given, the patient must be at least 14 days between last radiation treatment and 1st dose of rituximab
•Able to take daily aspirin (325 mg) for the duration of INCB7839 treatment and 1 week after the last dose to reduce the risk of thrombosis (not applicable if on other anti-coagulant therapy at time of study enrollment)
+3 more criteria

Exclusion Criteria

•Pregnant or lactating - Studies to evaluate the potential for embryo toxicity and teratogenicity have not been performed for INCB7839. Until additional information is available, women of childbearing potential should use appropriate precautions to avoid becoming pregnant. Rituximab is Pregnancy Category C: There are no adequate and well-controlled studies of rituximab in pregnant women. Females of childbearing potential must have a negative urine or serum pregnancy test within 14 days of study treatment start
•Recent venous thrombosis within 4 weeks prior to study enrollment. Patients at high risk for thrombotic events due to inherited risk factors (i.e. factor V Leiden) or DVT/PE in the past 12 months should be on secondary prophylaxis with anti-coagulant therapy (i.e. warfarin or low molecular weight heparin) prior to enrollment
•Active uncontrolled infection
•Active CNS disease
•Previous severe or life-threatening allergic reaction with rituximab or known allergy to the compounds found in INCB7839
•Any gastrointestinal condition causing malabsorption or obstruction (eg, celiac sprue, gastric bypass surgery, strictures, adhesions, history of small bowel resection, blind loop syndrome)
•Unwilling or unable to swallow tablets BID
•Serologic or clinical evidence of current active hepatitis B or C infection, defined as elevated levels of Hep B antigen or Hep C antibody (unless active infection is ruled out by nucleic acid tests)
•Known HIV infection

Locations (1)

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, United States

Key Dates

Start Date

May 1, 2014

Primary Completion Date

January 23, 2019

Completion Date

June 1, 2019

Last Updated

February 19, 2020

Enrollment

ACTUAL participants

Conditions

Diffuse Large B Cell Non-Hodgkin Lymphoma

Interventions

Rituximab

DRUG

INCB7839

DRUG

A Combination of Rituximab and CC-99282 as Front-line Therapy for Older Frail Patients With Diffuse Large B-cells Non-Hodgkin Lymphoma Evaluated With a Simplified Geriatric Assessment (sGA): a Phase II Study of the Fondazione Italiana Linfomi (FIL)

NCT06835530

Diffuse Large B Cell Non-Hodgkin Lymphoma

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 19, 2020Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

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