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ADAM17 Inhibitor/ Rituximab After Auto HCT for DLBCL

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ClinicalTrials.gov Identifier: NCT02141451
Recruitment Status : Active, not recruiting
First Posted : May 19, 2014
Last Update Posted : January 28, 2019
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE May 15, 2014
First Posted Date  ICMJE May 19, 2014
Last Update Posted Date January 28, 2019
Study Start Date  ICMJE May 2014
Actual Primary Completion Date January 23, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2014)
  • Maximum Tolerated Dose of INCB7839 [ Time Frame: 2 weeks ]
    The Phase I design will continue until the MTD is declared or until the first dose is declared to be above MTD. Phase I dose limiting toxicity (DLT) is defined as Grade 3-5 non-hematologic, non-infectious toxicity including thromboembolic complications and select hematologic events including: grade 4 neutropenia lasting for ≥ 7 days, febrile neutropenia, grade 4 thrombocytopenia lasting ≥ 7 days despite dose delay or grade 3 thrombocytopenia associated with bleeding.
  • Rate of progression free survival [ Time Frame: 6 months ]
    This Phase 2 primary end point will be estimated with Kaplan-Meier curves.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02141451 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2014)
  • Incidence of Serious Adverse Events [ Time Frame: 1 year ]
    To determine incidence of serious adverse events
  • Rate of disease free survival [ Time Frame: 1 year ]
    To evaluate 1 year disease-free survival
  • Rate of overall survival [ Time Frame: 1 year ]
    To evaluate 1 year overall survival
  • Mean time to progression [ Time Frame: 1 year ]
    To determine mean time to relapse/progression
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE ADAM17 Inhibitor/ Rituximab After Auto HCT for DLBCL
Official Title  ICMJE 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)
Brief 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.

Study Type  ICMJE Interventional
Study Phase Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diffuse Large B Cell Non-Hodgkin Lymphoma
Intervention  ICMJE
  • Drug: Rituximab
    Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later
    Other Name: Rituxan
  • Drug: INCB7839
    INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab
Study Arms Experimental: Treatment
Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab
Interventions:
  • Drug: Rituximab
  • Drug: INCB7839
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 24, 2019)
30
Original Estimated Enrollment  ICMJE
 (submitted: May 15, 2014)
33
Estimated Study Completion Date May 2020
Actual Primary Completion Date January 23, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
    • Hepatic: Alanine transaminase (ALT, SGPT) and aspartate aminotransferase (SGOT, AST) < 3 x upper limit of institutional normal and total bilirubin < 3.0 mg/dl (if total bilirubin is ≥ 3.0 patient is eligible if direct bilirubin is within normal limits)
    • 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)
  • Females are either postmenopausal for at least 1 year, are surgically sterile for at least 3 months, or must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through 12 months after the last dose of rituximab if of childbearing potential. (Note: Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed).
  • Males must agree to take appropriate precautions to avoid fathering a child (with at least 99% certainty) from screening through 12 months after the last dose of rituximab. (Note: Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed).
  • Voluntary written consent signed before performance of any study-related procedure not part of normal medical care

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02141451
Other Study ID Numbers  ICMJE 2013LS081
HM2013-24 ( Other Identifier: University of Minnesota Blood and Marrow Transplant Program )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Veronika Bachanova, MD University of Minnesota Medical Center, Fairview
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP