ADAM17 Inhibitor/ Rituximab After Auto HCT for DLBCL

NCT02141451 | Completed Phase 1 Results DMC

• 2 other identifiers: 2013LS081HM2013-24
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Diffuse Large B Cell Non-Hodgkin Lymphoma

Keywords

DLBCL

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicity Events

  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.

  2 weeks

• Number of Participants With Progression Free Survival at 6 Months

  This primary end point will be estimated with Kaplan-Meier curves.

  6 months

Secondary Outcomes (3)

• Incidence of Serious Adverse Events

  1 year

• Overall Survival

  1 year

• Time to Progression

  1 year

Study Arms (4)

INCB7839 100 mg (Phase I)

EXPERIMENTAL

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 Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab

Drug: Rituximab; Drug: INCB7839

INCB7839 200 mg (Phase I)

EXPERIMENTAL

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 Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab

Drug: Rituximab; Drug: INCB7839

INCB7839 300 mg (Phase I)

EXPERIMENTAL

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 Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab

Drug: Rituximab; Drug: INCB7839

INCB7839 (Phase II)

EXPERIMENTAL

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 Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab

Drug: Rituximab; Drug: INCB7839

Interventions

Rituximab DRUG

Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later

Also known as: Rituxan

INCB7839 (Phase II); INCB7839 100 mg (Phase I); INCB7839 200 mg (Phase I); INCB7839 300 mg (Phase I)

INCB7839 DRUG

INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab

INCB7839 (Phase II); INCB7839 100 mg (Phase I); INCB7839 200 mg (Phase I); INCB7839 300 mg (Phase I)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Interventions

Rituximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Veronika Bachanova
• Organization: Masonic Cancer Center, University of Minnesota

bach0173@umn.edu

612-625-5469

Study Officials

• Veronika Bachanova, MD

  University of Minnesota Medical Center, Fairview

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A Fast-Track Design with 1 patient enrolled per dose level until a grade 2 or greater treatment emergent adverse event occurs. A treatment emergent adverse event is any event not present prior to the initiation of the treatment (INCB7839) or any event already present that worsens in either intensity or frequency following exposure to the treatment. At that point, dose escalation will convert to a standard 3+3 design with two additional patients enrolled at the same 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 300mg bid, 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 Record Dates

• First Submitted: May 15, 2014
• First Posted: May 19, 2014
• Study Start: May 1, 2014
• Primary Completion: January 23, 2019
• Study Completion: June 1, 2019
• Last Updated: February 19, 2020
• Results First Posted: February 19, 2020

Record last verified: 2020-02

Locations

US (1)