ADAM17 Inhibitor/ Rituximab After Auto HCT for DLBCL

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT02141451
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 4
• Duration (Months): 61
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B Cell Non-Hodgkin Lymphoma	Drug: Rituximab; Drug: INCB7839	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: 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.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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Jan 23, 2019
• Actual Study Completion Date: Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INCB7839 100 mg (Phase I) 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; Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later; Other Names: Rituxan ; Drug: INCB7839; INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab
Experimental: INCB7839 200 mg (Phase I) 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; Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later; Other Names: Rituxan ; Drug: INCB7839; INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab
Experimental: INCB7839 300 mg (Phase I) 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; Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later; Other Names: Rituxan ; Drug: INCB7839; INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab
Experimental: INCB7839 (Phase II) 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; Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later; Other Names: Rituxan ; Drug: INCB7839; INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose Limiting Toxicity Events [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.

2. Number of Participants With Progression Free Survival at 6 Months [6 months]

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

Secondary Outcome Measures

1. Incidence of Serious Adverse Events [1 year]

   To determine incidence of serious adverse events

2. Overall Survival [1 year]

   To evaluate 1 year overall survival

3. Time to Progression [1 year]

   Time to relapse/progression in days

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Minnesota Medical Center, Fairview	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Veronika Bachanova, MD, University of Minnesota Medical Center, Fairview

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 12, 2018

More Information

Publications

None provided.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT02141451
• Other Study ID Numbers: 2013LS081; HM2013-24
• First Posted: May 19, 2014
• Last Update Posted: Feb 19, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Masonic Cancer Center, University of Minnesota: DLBCL
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Rituximab

Study Results

Participant Flow

Arm/Group Title	INCB7839 100 mg (Phase I)	INCB7839 200 mg (Phase I)	INCB7839 300 mg (Phase I)	INCB7839 300 mg (Phase II)
Arm/Group Description	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	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	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	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
Period Title: Overall Study
STARTED	3	4	7	16
COMPLETED	3	2	2	7
NOT COMPLETED	0	2	5	9

Baseline Characteristics

Arm/Group Title	INCB7839 100 mg (Phase I)	INCB7839 200 mg (Phase I)	INCB7839 300 mg (Phase I)	INCB7839 300 mg (Phase II)	Total
Arm/Group Description	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	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	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	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	Total of all reporting groups
Overall Participants	3	4	7	16	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	3 75%	4 57.1%	10 62.5%	20 66.7%
>=65 years	0 0%	1 25%	3 42.9%	6 37.5%	10 33.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.67 (4.78)	59.25 (8.79)	53.86 (14.67)	57.19 (11)	56.93 (11.45)
Sex: Female, Male (Count of Participants)
Female	3 100%	1 25%	2 28.6%	7 43.8%	13 43.3%
Male	0 0%	3 75%	5 71.4%	9 56.3%	17 56.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	3 100%	4 100%	7 100%	16 100%	30 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	3 100%	4 100%	7 100%	16 100%	30 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%	4 100%	7 100%	16 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicity Events
Description	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.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	INCB7839 100 mg (Phase I)	INCB7839 200 mg (Phase I)	INCB7839 300 mg (Phase I)
Arm/Group Description	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	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	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
Measure Participants	3	4	7
Count of Participants [Participants]	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With Progression Free Survival at 6 Months
Description	This primary end point will be estimated with Kaplan-Meier curves.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	INCB7839 100 mg (Phase I)	INCB7839 200 mg (Phase I)	INCB7839 300 mg (Phase I)	INCB7839 300 mg (Phase II)
Arm/Group Description	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	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	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	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
Measure Participants	3	4	7	16
Count of Participants [Participants]	3 100%	3 75%	6 85.7%	15 93.8%

3. Secondary Outcome

Title	Incidence of Serious Adverse Events
Description	To determine incidence of serious adverse events
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	INCB7839 100 mg (Phase I)	INCB7839 200 mg (Phase I)	INCB7839 300 mg (Phase I)	INCB7839 300 mg (Phase II)
Arm/Group Description	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	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	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	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
Measure Participants	3	4	7	16
Count of Participants [Participants]	0 0%	0 0%	1 14.3%	3 18.8%

4. Secondary Outcome

Title	Overall Survival
Description	To evaluate 1 year overall survival
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	INCB7839 100 mg (Phase I)	INCB7839 200 mg (Phase I)	INCB7839 300 mg (Phase I)	INCB7839 300 mg (Phase II)
Arm/Group Description	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	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	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	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
Measure Participants	3	4	7	16
Count of Participants [Participants]	3 100%	3 75%	7 100%	16 100%

5. Secondary Outcome

Title	Time to Progression
Description	Time to relapse/progression in days
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Only 3 participants experienced disease progression by 1 year on study

Arm/Group Title	INCB7839 100 mg (Phase I)	INCB7839 200 mg (Phase I)	INCB7839 300 mg (Phase I)	INCB7839 300 mg (Phase II)
Arm/Group Description	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	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	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	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
Measure Participants	0	1	1	1
Number [days]	105	136	259

Adverse Events

Time Frame	105 days or 1 week after last dose of INCB7839 if it is discontinued earlier
Arm/Group Title	INCB7839 100 mg (Phase I)		INCB7839 200 mg (Phase I)		INCB7839 300 mg (Phase I)		INCB7839 300 mg (Phase II)
Arm/Group Description	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		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		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		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
All Cause Mortality
	INCB7839 100 mg (Phase I)		INCB7839 200 mg (Phase I)		INCB7839 300 mg (Phase I)		INCB7839 300 mg (Phase II)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		1/4 (25%)		2/7 (28.6%)		2/16 (12.5%)
Serious Adverse Events
	INCB7839 100 mg (Phase I)		INCB7839 200 mg (Phase I)		INCB7839 300 mg (Phase I)		INCB7839 300 mg (Phase II)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/4 (0%)		1/7 (14.3%)		3/16 (18.8%)
General disorders
Pain	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Infections and infestations
Norovirus and C-Diff	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian Cancer	0/3 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/16 (0%)	0
Vascular disorders
Thromboembolic event	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Other (Not Including Serious) Adverse Events
	INCB7839 100 mg (Phase I)		INCB7839 200 mg (Phase I)		INCB7839 300 mg (Phase I)		INCB7839 300 mg (Phase II)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/4 (75%)		7/7 (100%)		15/16 (93.8%)
Blood and lymphatic system disorders
Anemia	0/3 (0%)	0	1/4 (25%)	1	0/7 (0%)	0	2/16 (12.5%)	4
D-dimer increased	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Ear and labyrinth disorders
External ear pain	0/3 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/16 (0%)	0
Eye disorders
Eye pain	0/3 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/16 (0%)	0
Gastrointestinal disorders
Abdominal Pain	2/3 (66.7%)	2	0/4 (0%)	0	0/7 (0%)	0	0/16 (0%)	0
Diarrhea	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	8/16 (50%)	15
Dry Mouth	0/3 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	2/16 (12.5%)	2
Dysphagia	0/3 (0%)	0	1/4 (25%)	1	0/7 (0%)	0	0/16 (0%)	0
Gastroesophageal reflux disease	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Nausea	0/3 (0%)	0	1/4 (25%)	1	0/7 (0%)	0	8/16 (50%)	12
Vomiting	0/3 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	2	3/16 (18.8%)	5
General disorders
Chills	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	2/16 (12.5%)	2
Fatigue	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	3/16 (18.8%)	4
Leg cramps	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Restless legs / leg pain	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Pain	0/3 (0%)	0	1/4 (25%)	1	2/7 (28.6%)	2	6/16 (37.5%)	13
Immune system disorders
Allergic Reaction	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Infections and infestations
C. difficile	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Norovirus	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Shingles	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Infection - HSV	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Infection - VZV	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Sinusitis	0/3 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	1/16 (6.3%)	1
Upper respiratory infection	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	2/16 (12.5%)	2
Investigations
Alanine aminotransferase increased	0/3 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	2/16 (12.5%)	4
Alkaline phosphate increased	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Aspartate aminotransferase increased	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	2/16 (12.5%)	2
D-dimer increased	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Lymphocyte count decreased	3/3 (100%)	15	2/4 (50%)	3	1/7 (14.3%)	5	1/16 (6.3%)	1
Neutrophil count decreased	3/3 (100%)	5	1/4 (25%)	2	1/7 (14.3%)	2	4/16 (25%)	6
Platelet count decreased	0/3 (0%)	0	1/4 (25%)	1	3/7 (42.9%)	4	3/16 (18.8%)	10
Vital capacity abnormal	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Weight gain	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Weight loss	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	4/16 (25%)	5
White blood cell decreased	3/3 (100%)	8	1/4 (25%)	2	1/7 (14.3%)	1	5/16 (31.3%)	8
Metabolism and nutrition disorders
Anorexia	0/3 (0%)	0	0/4 (0%)	0	3/7 (42.9%)	4	7/16 (43.8%)	9
Hypocalcemia	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Hypomagnesemia	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Musculoskeletal and connective tissue disorders
Arthalgia	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	3/16 (18.8%)	5
Back pain	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Generalized muscle weakness (hands)	0/3 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/16 (0%)	0
Myalgia	0/3 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	5/16 (31.3%)	6
Pain in extremity	0/3 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	1/16 (6.3%)	1
Nervous system disorders
Akathisia	0/3 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/16 (0%)	0
Headache	1/3 (33.3%)	1	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Syncope	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Psychiatric disorders
Depression	0/3 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	2	0/16 (0%)	0
Renal and urinary disorders
Acute Kidney Injury	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	2
Dyspnea	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Hypoxia	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Laryngeal inflammation	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders
Pain of skin	0/3 (0%)	0	0/4 (0%)	0	1/7 (14.3%)	1	0/16 (0%)	0
Rash-pruritic	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1
Vascular disorders
Hypertension	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	2/16 (12.5%)	3
Hypotension	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	2/16 (12.5%)	2
Thromboembolic event	0/3 (0%)	0	0/4 (0%)	0	0/7 (0%)	0	1/16 (6.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.