Phase 1/2 Dose Finding, Safety and Efficacy Study of Ibrutinib in Pediatric Subjects with Chronic Graft Versus Host Disease (cGVHD)
- Conditions
- Chronic Graft Versus Host Disease
- Registration Number
- NL-OMON54762
- Lead Sponsor
- Pharmacyclics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 2
1. Part A: Subjects with moderate or severe cGVHD after failure of 1
or more lines of systemic therapy.
2. Part B: Subjects with moderate or severe cGVHD after failure of 1
or more lines of systemic therapy, or subjects with new onset
moderate or severe cGVHD and in need of systemic
immunosuppression.
a. Subjects with new onset moderate or severe cGVHD must not
have received previous systemic therapy for cGVHD with the
exception of corticosteroids received within 72 hours prior to
signing the informed consent form.
b. Subjects with newly diagnosed cGVHD may be receiving
other immunosuppressants for the prophylaxis or treatment of
acute GVHD, but if the subject is receiving prednisone for
prophylaxis or treatment of acute GVHD it must be at or below
0.5 mg/kg/d at the time of enrollment.
3. History of allogeneic stem cell transplantation
4. Age
• Part A: >=1 to <12 years of age at the time of enrollment
• Part B: >=1 to <22 years of age at the time of enrollment
5.Written informed consent or parental or guardian permission and
assent of children capable of understanding the nature of the study,
per country-specific or site-specific standards
6. Ability of subject or, if a minor, parent/guardian to understand the
purpose and risks of the study and to provide a signed and dated
parental permission and authorization to use protected health
information (in accordance with national and local subject privacy
regulations); willingness of child to provide an assent, if
developmentally able to do so.
Disease-Related
1. Presence of single organ genito-urinary involvement as the only
manifestation of cGVHD.
Concurrent Conditions
2. Received an investigational agent within 28 days before enrollment.
3. Received donor lymphocyte infusion (DLI) within 56 days before
enrollment.
4. Progressive underlying malignant disease or active post-transplant
lymphoproliferative disease.
5. Ongoing anticoagulation treatment with warfarin or equivalent
vitamin K antagonist.
6. History of other malignancy (not including the underlying
malignancy that was the indication for transplant), with the
following exceptions:
• Malignancy treated with curative intent and with no evidence of
active disease present for more than 3 years prior to enrollment
and felt to be at low risk for recurrence by treating physician
• Adequately treated non-melanomatous skin cancer or lentigo
maligna melanoma without current evidence of disease
• Adequately treated cervical carcinoma in situ without current
evidence of disease
7. History of major surgery within 28 days before enrollment or lack
of full recovery from surgery.
8. Any life-threatening illness, medical condition, or organ system
dysfunction that, in the investigator*s opinion, could compromise
the subject*s safety or put the study outcomes at undue risk.
9. Female subject who is pregnant, breastfeeding, or planning to
become pregnant while enrolled in this study or within 3 months of
the last dose of study drug. Male subject who plans to father a child
while enrolled in this study or within 3 months after the last dose of
study drug.
10. Unwilling or unable to participate in all required study evaluations
and procedures.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoints:<br /><br>Part A: PK (area under the plasma concentration-time curve [AUC]) to determine<br /><br>the RPED of ibrutinib for use in pediatric subjects (age >= 1 to<br /><br>< 12 years) with cGVHD.<br /><br>Part B: PK (AUC) and safety (treatment-emergent AEs and laboratory<br /><br>abnormalities) of ibrutinib in pediatric subjects (age >= 1 and < 22 years)<br /><br>with cGVHD.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints:<br /><br><br /><br>Part A:<br /><br>* Safety, including treatment-emergent AEs, laboratory abnormalities and other<br /><br>safety endpoints.<br /><br>* Pharmacodynamics (Bruton*s tyrosine kinase occupancy)<br /><br>* For those subjects continuing therapy after dose escalation (Part A<br /><br>Continuation Cohort), secondary endpoints will be the same as<br /><br>outlined under Part B below.<br /><br><br /><br>Part B:<br /><br>* Response rate at 24 weeks<br /><br>* Duration of response<br /><br>* Overall survival rate<br /><br>* Growth and development<br /><br>* Immune reconstitution</p><br>