This study is currently recruiting participants.
Number
000643-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Fetuses;Pregnant Women;Children
Keywords
Anti-Inflammatory; Fibrosis; Inflammation; Refractory; Systemic Therapy
Recruitment Keyword(s)
None
Condition(s)
Graft vs Host Disease
Investigational Drug(s)
Pacritinib
Investigational Device(s)
Intervention(s)
Drug: Pacritinib
Supporting Site
National Cancer Institute
Chronic graft-versus-host disease (cGVHD) is an immune system disorder that can occur in people who have had a stem cell transplant. cGVHD can affect multiple organs and increase risk of disability and death. New treatments are needed to treat cGVHD after stem cell transplant.
Objective:
To test a drug (pacritinib) in people with moderate or severe cGVHD that has not responded to previous treatment.
Eligibility:
People aged 18 years and older with moderate or severe cGVHD that has not responded to 2 or more lines of previous treatment.
Design:
Participants will be screened. They will have blood and urine tests. They will have tests of their heart and lung function. They may also have a CT scan. Some may have other specialized tests.
Participants will take the study drug at home every day. Pacritinib is a capsule taken by mouth. The study doctor will determine the dosage and schedule.
Participants will keep a medication diary. They will record the date and time of each drug dose and any missed doses.
Participants will visit the clinic every 2 weeks for the first 4 months. Then they will visit the clinic once every 4 weeks. They will have blood and urine tests. During some visits, other screening tests will be repeated, and participants will fill out questionnaires about their quality of life. Photographs may be taken of skin rashes and joints affected by cGVHD.
Participants will give saliva samples. Optional biopsies may be taken of the skin and mouth.
Participants will take pacritinib for 6 to 12 months if no side effects develop. Follow-up visits will continue for up to 2 years.
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INCLUSION CRITERIA: 1.Moderate or severe cGVHD (after allogeneic hematopoietic stem cell transplantation) diagnosed and staged per NIH criteria 2. cGVHD that did not respond to greater than or equal to 2 lines of prior systemic therapy. Disease that has failed prior systemic therapy will be defined as follows: a) For prior corticosteroid-containing regimens, disease that: i) recurs after achievement of a CR, or ii) progresses after achievement of a PR, or iii) progresses after at least 1 week of prednisone equivalent of 1 mg/kg/day, or iv) is stable and persistent after at least 4 weeks of a prednisone equivalent of 0.5 mg/kg/day OR, b) For other systemic therapies, disease that: i) recurs after achievement of CR, or ii) progresses after achievement of a PR, or iii) is stable and persistent despite 4 weeks of therapeutic dosing of systemic therapy 3. Karnofsky performance score greater than or equal to 60% 4. Age >=18 years. 5. If participant is taking systemic therapy for cGVHD at the time of enrollment, they must be on a stable or tapering dose in the preceding 4 weeks. 6. Participants must have adequate organ and marrow function as defined below: -absolute neutrophil count >=1,000/mcL -platelets >=50,000/mcL -total bilirubin <=1.5 X institutional upper limit of normal OR <=3 X institutional upper limit of normal in participants with Gilbert s syndrome -AST(SGOT)/ALT(SGPT) <=3 X institutional upper limit of normal -creatinine clearance >=50 mL/min/1.73 m^2 per Cockroft-Gault 7. Primary malignancy for which the participant received transplant has been in complete clinical remission and stable for 3 months prior to enrollment on study. 8. Women of child-bearing potential and men who are sexually active must agree to use one (1) highly effective (e.g., intrauterine device [IUD], hormonal, surgical) or two (2)effective forms of contraception (e.g., barrier method) at study entry, for the duration of study treatment, and for at least 30 days after last study drug exposure. 9. Ability of participant to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: 1. Acute GVHD that is active as defined by exhibiting current signs or symptoms of disease without any chronic GVHD (classic and late-acute GVHD per NIH consensus criteria); participants with a clinical presentation consistent with overlapping acute GVHD with concurrent chronic GVHD will be eligible 2. Treatment with ruxolitinib, or ibrutinib within the for <= 14 days prior to treatment initiation. 3. Active HIV-1 (detectable HIV viral load), or Hepatitis B (HBV) and/or Hepatitis C (HCV) infection (positive HBV or HCV viral load in the setting of positive HBV core antibody or surface antibody or HCV antibody). 4. Participants with the following cardiac conditions at screening: -symptomatic congestive heart failure -unstable angina pectoris -uncontrolled cardiac dysrhythmias -QTc(F) prolongation >450 ms or other factors that increase the risk for QT prolongation (i.e., heart failure, or a history of long QT interval syndrome). 5. Left ventricular ejection fraction <= 50% by transthoracic echocardiogram (TTE) at screening. 6. Participants with poor pulmonary function as defined by a forced expiratory volume in the first second (FEV1) <= 39% calculated using the USA-ITS-NIH equation. 7. Participants with evidence of ongoing hemorrhage, active signs/symptoms of bleeding, or history of severe bleeding complications in the one year prior to enrollment. 8. Concurrent treatment with any other investigational agents. 9. Concurrent use of strong CYP3A4 inducers or inhibitors, must stop 2 weeks prior study drug initiation. 10. Known hypersensitivity to JAK inhibitors. 11. Participants who are unwilling to accept blood transfusions. 12. Pregnancy or breastfeeding. 13. Participants with any active, uncontrolled viral, bacterial, or fungal infection are excluded. 14. Other malignancy except non-melanoma skin cancer or carcinoma in situ of the cervix or breast which requires active treatment. 15. Uncontrolled intercurrent illness evaluated by history, physical exam and chemistries or situation that would limit compliance with study requirements.
1.Moderate or severe cGVHD (after allogeneic hematopoietic stem cell transplantation) diagnosed and staged per NIH criteria
2. cGVHD that did not respond to greater than or equal to 2 lines of prior systemic therapy.
Disease that has failed prior systemic therapy will be defined as follows:
a) For prior corticosteroid-containing regimens, disease that:
i) recurs after achievement of a CR, or
ii) progresses after achievement of a PR, or
iii) progresses after at least 1 week of prednisone equivalent of 1 mg/kg/day, or
iv) is stable and persistent after at least 4 weeks of a prednisone equivalent of 0.5 mg/kg/day
OR,
b) For other systemic therapies, disease that:
i) recurs after achievement of CR, or
iii) is stable and persistent despite 4 weeks of therapeutic dosing of systemic therapy
3. Karnofsky performance score greater than or equal to 60%
4. Age >=18 years.
5. If participant is taking systemic therapy for cGVHD at the time of enrollment, they must be on a stable or tapering dose in the preceding 4 weeks.
6. Participants must have adequate organ and marrow function as defined below:
-absolute neutrophil count >=1,000/mcL
-platelets >=50,000/mcL
-total bilirubin <=1.5 X institutional upper limit of normal
OR
<=3 X institutional upper limit of normal in participants with Gilbert s syndrome
-AST(SGOT)/ALT(SGPT) <=3 X institutional upper limit of normal
-creatinine clearance >=50 mL/min/1.73 m^2 per Cockroft-Gault
7. Primary malignancy for which the participant received transplant has been in complete clinical remission and stable for 3 months prior to enrollment on study.
8. Women of child-bearing potential and men who are sexually active must agree to use one (1) highly effective (e.g., intrauterine device [IUD], hormonal, surgical) or two (2)effective forms of contraception (e.g., barrier method) at study entry, for the duration of study treatment, and for at least 30 days after last study drug exposure.
9. Ability of participant to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
1. Acute GVHD that is active as defined by exhibiting current signs or symptoms of disease without any chronic GVHD (classic and late-acute GVHD per NIH consensus criteria); participants with a clinical presentation consistent with overlapping acute GVHD with concurrent chronic GVHD will be eligible
2. Treatment with ruxolitinib, or ibrutinib within the for <= 14 days prior to treatment initiation.
3. Active HIV-1 (detectable HIV viral load), or Hepatitis B (HBV) and/or Hepatitis C (HCV) infection (positive HBV or HCV viral load in the setting of positive HBV core antibody or surface antibody or HCV antibody).
4. Participants with the following cardiac conditions at screening:
-symptomatic congestive heart failure
-unstable angina pectoris
-uncontrolled cardiac dysrhythmias
-QTc(F) prolongation >450 ms or other factors that increase the risk for QT prolongation (i.e., heart failure, or a history of long QT interval syndrome).
5. Left ventricular ejection fraction <= 50% by transthoracic echocardiogram (TTE) at screening.
6. Participants with poor pulmonary function as defined by a forced expiratory volume in the first second (FEV1) <= 39% calculated using the USA-ITS-NIH equation.
7. Participants with evidence of ongoing hemorrhage, active signs/symptoms of bleeding, or history of severe bleeding complications in the one year prior to enrollment.
8. Concurrent treatment with any other investigational agents.
9. Concurrent use of strong CYP3A4 inducers or inhibitors, must stop 2 weeks prior study drug initiation.
10. Known hypersensitivity to JAK inhibitors.
11. Participants who are unwilling to accept blood transfusions.
12. Pregnancy or breastfeeding.
13. Participants with any active, uncontrolled viral, bacterial, or fungal infection are excluded.
14. Other malignancy except non-melanoma skin cancer or carcinoma in situ of the cervix or breast which requires active treatment.
15. Uncontrolled intercurrent illness evaluated by history, physical exam and chemistries or situation that would limit compliance with study requirements.
Principal Investigator
Referral Contact
For more information: