Chronic Graft-versus-host-diseasePhase 1/2NCT03689894
Ibrutinib Plus Rituximab for cGVHD Following Allo-SCT
A Phase 1/2 study testing Ibrutinib and Rituximab in people with Chronic Graft-versus-host-disease, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
Trial summary
Allogeneic stem cell transplant is used to treat a variety of blood cancers. However, graft-versus-host disease (GVHD) is a common condition that may occur after transplant. GVHD happens when the donor cells attack and damage the recipients' tissue. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Graft-versus-host-disease
- What is being tested?
- Ibrutinib and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Apr 2019to 20 Sep 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women ≥18 years old who are recipients of an allogeneic bone marrow, cord blood or peripheral blood stem cell transplant. (There will be no restrictions based upon underlying disease, donor source, degree of human leukocyte antigen (HLA) match, intensity of pre-transplant conditioning regimen or use of prior donor lymphocyte infusion(s).)
- Chronic GVHD that is confirmed by clinical assessment and/or biopsy.
- Either steroid-refractory or steroid-dependent cGVHD.
- Karnofsky performance status ≥ 60.
Who cannot join
- History of treatment with a tyrosine kinase inhibitor (eg, imatinib) or other moderate-to-significant Cyclophilin A4 inhibitor within 2 weeks of enrollment.
- Renal insufficiency as follows: creatinine > 2.5 mg/deciliters (dL) or Creatinine Clearance < 30 ml/min.
- Hepatic insufficiency as follows: serum bilirubin >3 mg/dL or transaminitis >3x upper limit of normal (ULN) (unless deemed due to GVHD).
- History of cardiac dysrhythmias or known cardiovascular disease without formal Cardiology clearance.
- History of cerebro-vascular accident or intracranial hemorrhage within 6 months prior to enrollment.
- History of non-intracranial hemorrhage and/or coagulopathy without formal Coagulation clearance.
Show all 12Show fewer
- Uncontrolled infections not responsive to antibiotics, anti-viral medicines, or anti-fungal medicines; or infection requiring systemic treatment that was completed ≤14 days before enrollment.
- History of other hematologic malignancy.
- History of human immunodeficiency virus (HIV).
- History of active hepatitis B virus (HBV) or hepatitis C virus (HCV) without formal Infectious Disease clearance.
- Patients incapable of complying with routine follow up schedule or unable to be compliant with study therapy.
- Active or within 3 months use of prohibited medications or substances (e.g., illicit drugs).
Trial locations and contacts
1 site in 1 country.
United States1 site
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
About this study
Official title: Combination Ibrutinib and Rituximab for the Treatment of Chronic Graft-Versus-Host Disease Following Allogeneic Stem Cell Transplant
Allogeneic stem cell transplant is used to treat a variety of blood cancers. However, graft-versus-host disease (GVHD) is a common condition that may occur after transplant. GVHD happens when the donor cells attack and damage the recipients' tissue.
The standard medication to treat chronic graft-versus-host-disease (cGVHD) is corticosteroids. However, there are long-term side effects of steroid therapy, including risk of infection, bone loss and other health problems. In addition, some patients with cGVHD do not respond to standard steroid therapy. In these cases, medications to suppress the immune system may be used.
Read more
The purpose of this study is to learn about the effects, both good and bad, of combining the drugs ibrutinib and rituximab for the treatment of cGVHD.
Ibrutinib is Food and Drug Administration (FDA)-approved for the treatment of cGVHD which has not responded to steroid therapy.
Rituximab is an investigational drug, which means it is not FDA approved for this particular use. Rituximab is currently approved for treatment of Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), and other conditions, but is not FDA approved for the treatment of cGVHD.
However, rituximab has been used in a clinic setting for the treatment of cGVHD in a number of patients over the past few years, and has generally been well tolerated and shown some benefit.
The combination of ibrutinib and rituximab is being studied in the treatment of certain types of lymphoma and chronic leukemia, but it has not yet been combined for patients with cGVHD. Because ibrutinib is not approved for this use when combined with rituximab, it is considered investigational in this study.
In this form, the term "study drug" refers to ibrutinib and rituximab.
This study will involve people who have chronic GVHD, have previously taken corticosteroids, and have either not benefited from treatment with corticosteroids or have been unable to successfully taper off steroids.
- Conditions
- Chronic Graft-versus-host-disease
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Subjects will receive oral (PO) Ibrutinib 140 mg once daily with Rituximab 375 mg per meter squared IV weekly x4 (with pre-medications and infusion procedure as per standard protocol) Rituximab Pre-medications:Acetaminophen 650 mg PO; Diphenhydramine 25 mg PO/IV; Dexamethasone 20 mg IV.
If no adverse events >Grade 3+ are noted after 1 week, the Ibrutinib dose schedule will be increased to 280 mg daily. If no adverse events >Gr3+ are noted after an additional 1 week, the Ibrutinib dose will be increased to 420 mg daily.
RituximabDrug
Subject will receive an intravenous infusion of 375mg per meter squared weekly for 4 weeks, which may be repeated 8 weeks after initial therapy if only a suboptimal response is achieved.
| Study group | Role | What they receive |
|---|---|---|
| Ibrutinib plus Rituximab | Experimental | Rituximab
*375 milligrams (mg) per meter squared intravenous infusion weekly for 4 (may repeat 8 weeks after initial therapy, if suboptimal response)
Ibrutinib
* 420 mg (140 mg capsule x3) by mouth daily
* May be given beyond 3-6 months (for maintenance). Receives: Drug: Ibrutinib; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate Dose-limiting Toxicities Experienced in Subjects Treated With Ibrutinib Plus Rituximab
During dose escalation, subjects will be assessed for dose-limiting toxicities at each dose level.
Measured: Start of treatment through Week 4 of treatment
Secondary outcomes (2)
Assess the Response Rate of cGVHD to Treatment With Ibrutinib Plus Rituximab
Response rate of clinically significant GVHD will be assessed using NIH criteria (from 2014 NIH Consensus Development Project).
Measured: 6 weeks, 3 months, and 6 months after initiation of treatment
Identify Relevant Laboratory Correlates Underlying Clinical Response, or Lack Thereof.
Plasma ST2 and CD4CD25FOXp3 correlates will be measured at identified intervals to determine if either correlate demonstrates an affect on clinical response.
Measured: 6 weeks, 3 months, and 6 months after initiation of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2018
- Study start11 Apr 2019
- Primary completion20 Sep 2021
- Study completion20 Sep 2021
Why it stopped: Insufficient accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for Chronic Graft-versus-host-diseaseStudies of the same condition, open and under way.
- More trials run by Dartmouth-Hitchcock Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John M. Hill, Jr., MD, Dartmouth-Hitchcock Medical Center
- Investigators
- John M Hill, MD, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03689894
- Sponsor's protocol ID
- D17120
- Status last verified
- Nov 2023
- First submitted
- 27 Sep 2018
- Last updated
- 28 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jaglowski SM, Devine SM. Graft-versus-host disease: why have we not made more progress? Curr Opin Hematol. 2014 Mar;21(2):141-7. doi: 10.1097/MOH.0000000000000026.
PubMed 24468835Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.
PubMed 16338616Wolff D, Schleuning M, von Harsdorf S, Bacher U, Gerbitz A, Stadler M, Ayuk F, Kiani A, Schwerdtfeger R, Vogelsang GB, Kobbe G, Gramatzki M, Lawitschka A, Mohty M, Pavletic SZ, Greinix H, Holler E. Consensus Conference on Clinical Practice in Chronic GVHD: Second-Line Treatment of Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2011 Jan;17(1):1-17. doi: 10.1016/j.bbmt.2010.05.011. Epub 2010 May 26.
PubMed 20685255Sarantopoulos S, Blazar BR, Cutler C, Ritz J. B cells in chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2015 Jan;21(1):16-23. doi: 10.1016/j.bbmt.2014.10.029. Epub 2014 Nov 12.
PubMed 25452031Cutler C, Miklos D, Kim HT, Treister N, Woo SB, Bienfang D, Klickstein LB, Levin J, Miller K, Reynolds C, Macdonell R, Pasek M, Lee SJ, Ho V, Soiffer R, Antin JH, Ritz J, Alyea E. Rituximab for steroid-refractory chronic graft-versus-host disease. Blood. 2006 Jul 15;108(2):756-62. doi: 10.1182/blood-2006-01-0233. Epub 2006 Mar 21.
PubMed 16551963Arai S, Sahaf B, Narasimhan B, Chen GL, Jones CD, Lowsky R, Shizuru JA, Johnston LJ, Laport GG, Weng WK, Benjamin JE, Schaenman J, Brown J, Ramirez J, Zehnder JL, Negrin RS, Miklos DB. Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence. Blood. 2012 Jun 21;119(25):6145-54. doi: 10.1182/blood-2011-12-395970. Epub 2012 May 4.
PubMed 22563089Cutler C, Kim HT, Bindra B, Sarantopoulos S, Ho VT, Chen YB, Rosenblatt J, McDonough S, Watanaboonyongcharoen P, Armand P, Koreth J, Glotzbecker B, Alyea E, Blazar BR, Soiffer RJ, Ritz J, Antin JH. Rituximab prophylaxis prevents corticosteroid-requiring chronic GVHD after allogeneic peripheral blood stem cell transplantation: results of a phase 2 trial. Blood. 2013 Aug 22;122(8):1510-7. doi: 10.1182/blood-2013-04-495895. Epub 2013 Jul 16.
PubMed 23861248Krenger W, Ferrara JL. Graft-versus-host disease and the Th1/Th2 paradigm. Immunol Res. 1996;15(1):50-73. doi: 10.1007/BF02918284.
PubMed 8739565Dubovsky JA, Beckwith KA, Natarajan G, Woyach JA, Jaglowski S, Zhong Y, Hessler JD, Liu TM, Chang BY, Larkin KM, Stefanovski MR, Chappell DL, Frissora FW, Smith LL, Smucker KA, Flynn JM, Jones JA, Andritsos LA, Maddocks K, Lehman AM, Furman R, Sharman J, Mishra A, Caligiuri MA, Satoskar AR, Buggy JJ, Muthusamy N, Johnson AJ, Byrd JC. Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013 Oct 10;122(15):2539-49. doi: 10.1182/blood-2013-06-507947. Epub 2013 Jul 25.
PubMed 23886836Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, Chang BY, Sukbuntherng J, Izumi R, Hamdy A, Hedrick E, Fowler NH. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013 Jan 1;31(1):88-94. doi: 10.1200/JCO.2012.42.7906. Epub 2012 Oct 8.
PubMed 23045577Wang Y, Zhang LL, Champlin RE, Wang ML. Targeting Bruton's tyrosine kinase with ibrutinib in B-cell malignancies. Clin Pharmacol Ther. 2015 May;97(5):455-68. doi: 10.1002/cpt.85. Epub 2015 Apr 3.
PubMed 25669675Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Li L, Zhang L, Newberry K, Ou Z, Cheng N, Fang B, McGreivy J, Clow F, Buggy JJ, Chang BY, Beaupre DM, Kunkel LA, Blum KA. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013 Aug 8;369(6):507-16. doi: 10.1056/NEJMoa1306220. Epub 2013 Jun 19.
PubMed 23782157Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, Grant B, Sharman JP, Coleman M, Wierda WG, Jones JA, Zhao W, Heerema NA, Johnson AJ, Sukbuntherng J, Chang BY, Clow F, Hedrick E, Buggy JJ, James DF, O'Brien S. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013 Jul 4;369(1):32-42. doi: 10.1056/NEJMoa1215637. Epub 2013 Jun 19.
PubMed 23782158Schutt SD, Fu J, Nguyen H, Bastian D, Heinrichs J, Wu Y, Liu C, McDonald DG, Pidala J, Yu XZ. Inhibition of BTK and ITK with Ibrutinib Is Effective in the Prevention of Chronic Graft-versus-Host Disease in Mice. PLoS One. 2015 Sep 8;10(9):e0137641. doi: 10.1371/journal.pone.0137641. eCollection 2015.
PubMed 26348529Miklos D, Cutler CS, Arora M, Waller EK, Jagasia M, Pusic I, Flowers ME, Logan AC, Nakamura R, Blazar BR, Li Y, Chang S, Lal I, Dubovsky J, James DF, Styles L, Jaglowski S. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017 Nov 23;130(21):2243-2250. doi: 10.1182/blood-2017-07-793786. Epub 2017 Sep 18.
PubMed 28924018
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Ibrutinib and Rituximab for the Treatment of Chronic Graft-Versus-Host Disease Following Allogeneic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT03689894
- Acronym / sponsor ID
- D17120
- Conditions
- Chronic Graft-versus-host-disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient accrual
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Study start
- 11 Apr 2019 (actual)
- Primary completion
- 20 Sep 2021 (actual)
- Study completion
- 20 Sep 2021 (actual)
- First posted
- 1 Oct 2018 (actual)
- Results
- Posted 28 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Allogeneic stem cell transplant is used to treat a variety of blood cancers. However, graft-versus-host disease (GVHD) is a common condition that may occur after transplant. GVHD happens when the donor cells attack and damage the recipients' tissue.
The standard medication to treat chronic graft-versus-host-disease (cGVHD) is corticosteroids. However, there are long-term side effects of steroid therapy, including risk of infection, bone loss and other health problems. In addition, some patients with cGVHD do not respond to standard steroid therapy. In these cases, medications to suppress the immune system may be used.
The purpose of this study is to learn about the effects, both good and bad, of combining the drugs ibrutinib and rituximab for the treatment of cGVHD.
Ibrutinib is Food and Drug Administration (FDA)-approved for the treatment of cGVHD which has not responded to steroid therapy.
Rituximab is an investigational drug, which means it is not FDA approved for this particular use. Rituximab is currently approved for treatment of Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), and other conditions, but is not FDA approved for the treatment of cGVHD.
However, rituximab has been used in a clinic setting for the treatment of cGVHD in a number of patients over the past few years, and has generally been well tolerated and shown some benefit.
The combination of ibrutinib and rituximab is being studied in the treatment of certain types of lymphoma and chronic leukemia, but it has not yet been combined for patients with cGVHD. Because ibrutinib is not approved for this use when combined with rituximab, it is considered investigational in this study.
In this form, the term "study drug" refers to ibrutinib and rituximab.
This study will involve people who have chronic GVHD, have previously taken corticosteroids, and have either not benefited from treatment with corticosteroids or have been unable to successfully taper off steroids.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ibrutinib plus Rituximab | Experimental | Drug: Ibrutinib, Drug: RituximabRituximab *375 milligrams (mg) per meter squared intravenous infusion weekly for 4 (may repeat 8 weeks after initial therapy, if suboptimal response) Ibrutinib * 420 mg (140 mg capsule x3) by mouth daily * May be given beyond 3-6 months (for maintenance). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Men and women ≥18 years old who are recipients of an allogeneic bone marrow, cord blood or peripheral blood stem cell transplant. (There will be no restrictions based upon underlying disease, donor source, degree of human leukocyte antigen (HLA) match, intensity of pre-transplant conditioning regimen or use of prior donor lymphocyte infusion(s).)
- Chronic GVHD that is confirmed by clinical assessment and/or biopsy.
- Either steroid-refractory or steroid-dependent cGVHD.
- Karnofsky performance status ≥ 60.
Key exclusion criteria (12 listed)
- History of treatment with a tyrosine kinase inhibitor (eg, imatinib) or other moderate-to-significant Cyclophilin A4 inhibitor within 2 weeks of enrollment.
- Renal insufficiency as follows: creatinine > 2.5 mg/deciliters (dL) or Creatinine Clearance < 30 ml/min.
- Hepatic insufficiency as follows: serum bilirubin >3 mg/dL or transaminitis >3x upper limit of normal (ULN) (unless deemed due to GVHD).
- History of cardiac dysrhythmias or known cardiovascular disease without formal Cardiology clearance.
- History of cerebro-vascular accident or intracranial hemorrhage within 6 months prior to enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbrutinibSubjects will receive oral (PO) Ibrutinib 140 mg once daily with Rituximab 375 mg per meter squared IV weekly x4 (with pre-medications and infusion procedure as per standard protocol) Rituximab Pre-medications:Acetaminophen 650 mg PO; Diphenhydramine 25 mg PO/IV; Dexamethasone 20 mg IV. If no adverse events >Grade 3+ are noted after 1 week, the Ibrutinib dose schedule will be increased to 280 mg daily. If no adverse events >Gr3+ are noted after an additional 1 week, the Ibrutinib dose will be increased to 420 mg daily. | Drug | Ibrutinib plus Rituximab |
| RituximabSubject will receive an intravenous infusion of 375mg per meter squared weekly for 4 weeks, which may be repeated 8 weeks after initial therapy if only a suboptimal response is achieved. | Drug | Ibrutinib plus Rituximab |
Primary outcome
Evaluate Dose-limiting Toxicities Experienced in Subjects Treated With Ibrutinib Plus Rituximab
Time frame: Start of treatment through Week 4 of treatment
During dose escalation, subjects will be assessed for dose-limiting toxicities at each dose level.
2 secondary outcomes
Assess the Response Rate of cGVHD to Treatment With Ibrutinib Plus Rituximab
Time frame: 6 weeks, 3 months, and 6 months after initiation of treatment
Identify Relevant Laboratory Correlates Underlying Clinical Response, or Lack Thereof.
Time frame: 6 weeks, 3 months, and 6 months after initiation of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24468835Jaglowski SM, Devine SM. Graft-versus-host disease: why have we not made more progress? Curr Opin Hematol. 2014 Mar;21(2):141-7. doi: 10.1097/MOH.0000000000000026.
- Background: PubMed 16338616Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.
- Background: PubMed 20685255Wolff D, Schleuning M, von Harsdorf S, Bacher U, Gerbitz A, Stadler M, Ayuk F, Kiani A, Schwerdtfeger R, Vogelsang GB, Kobbe G, Gramatzki M, Lawitschka A, Mohty M, Pavletic SZ, Greinix H, Holler E. Consensus Conference on Clinical Practice in Chronic GVHD: Second-Line Treatment of Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2011 Jan;17(1):1-17. doi: 10.1016/j.bbmt.2010.05.011. Epub 2010 May 26.
- Background: PubMed 25452031Sarantopoulos S, Blazar BR, Cutler C, Ritz J. B cells in chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2015 Jan;21(1):16-23. doi: 10.1016/j.bbmt.2014.10.029. Epub 2014 Nov 12.
- Background: PubMed 16551963Cutler C, Miklos D, Kim HT, Treister N, Woo SB, Bienfang D, Klickstein LB, Levin J, Miller K, Reynolds C, Macdonell R, Pasek M, Lee SJ, Ho V, Soiffer R, Antin JH, Ritz J, Alyea E. Rituximab for steroid-refractory chronic graft-versus-host disease. Blood. 2006 Jul 15;108(2):756-62. doi: 10.1182/blood-2006-01-0233. Epub 2006 Mar 21.
- Background: PubMed 22563089Arai S, Sahaf B, Narasimhan B, Chen GL, Jones CD, Lowsky R, Shizuru JA, Johnston LJ, Laport GG, Weng WK, Benjamin JE, Schaenman J, Brown J, Ramirez J, Zehnder JL, Negrin RS, Miklos DB. Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence. Blood. 2012 Jun 21;119(25):6145-54. doi: 10.1182/blood-2011-12-395970. Epub 2012 May 4.
- Background: PubMed 23861248Cutler C, Kim HT, Bindra B, Sarantopoulos S, Ho VT, Chen YB, Rosenblatt J, McDonough S, Watanaboonyongcharoen P, Armand P, Koreth J, Glotzbecker B, Alyea E, Blazar BR, Soiffer RJ, Ritz J, Antin JH. Rituximab prophylaxis prevents corticosteroid-requiring chronic GVHD after allogeneic peripheral blood stem cell transplantation: results of a phase 2 trial. Blood. 2013 Aug 22;122(8):1510-7. doi: 10.1182/blood-2013-04-495895. Epub 2013 Jul 16.
- Background: PubMed 8739565Krenger W, Ferrara JL. Graft-versus-host disease and the Th1/Th2 paradigm. Immunol Res. 1996;15(1):50-73. doi: 10.1007/BF02918284.
- Background: PubMed 23886836Dubovsky JA, Beckwith KA, Natarajan G, Woyach JA, Jaglowski S, Zhong Y, Hessler JD, Liu TM, Chang BY, Larkin KM, Stefanovski MR, Chappell DL, Frissora FW, Smith LL, Smucker KA, Flynn JM, Jones JA, Andritsos LA, Maddocks K, Lehman AM, Furman R, Sharman J, Mishra A, Caligiuri MA, Satoskar AR, Buggy JJ, Muthusamy N, Johnson AJ, Byrd JC. Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013 Oct 10;122(15):2539-49. doi: 10.1182/blood-2013-06-507947. Epub 2013 Jul 25.
- Background: PubMed 23045577Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, Chang BY, Sukbuntherng J, Izumi R, Hamdy A, Hedrick E, Fowler NH. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013 Jan 1;31(1):88-94. doi: 10.1200/JCO.2012.42.7906. Epub 2012 Oct 8.
- Background: PubMed 25669675Wang Y, Zhang LL, Champlin RE, Wang ML. Targeting Bruton's tyrosine kinase with ibrutinib in B-cell malignancies. Clin Pharmacol Ther. 2015 May;97(5):455-68. doi: 10.1002/cpt.85. Epub 2015 Apr 3.
- Background: PubMed 23782157Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Li L, Zhang L, Newberry K, Ou Z, Cheng N, Fang B, McGreivy J, Clow F, Buggy JJ, Chang BY, Beaupre DM, Kunkel LA, Blum KA. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013 Aug 8;369(6):507-16. doi: 10.1056/NEJMoa1306220. Epub 2013 Jun 19.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John M Hill, MD principal investigator
Dartmouth-Hitchcock Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ibrutinib and Rituximab in people with Chronic Graft-versus-host-disease, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate Dose-limiting Toxicities Experienced in Subjects Treated With Ibrutinib Plus Rituximab (time frame: Start of treatment through Week 4 of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03689894, which also lists 26 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2023.