Ibrutinib in Combination With Corticosteroids vs Placebo in Combination With Corticosteroids in Participants With New Onset Chronic Graft Versus Host Disease (cGVHD) (iNTEGRATE)

Pharmacyclics

Status and phase: Completed; Phase 3

Conditions: Chronic Graft Versus Host Disease

Treatments: Drug: Prednisone; Drug: Placebo; Drug: ibrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02959944

PCYC-1140-IM

Details and patient eligibility

About

To evaluate the safety and efficacy of ibrutinib in combination with prednisone in subjects with newly diagnosed moderate to severe cGVHD.

Enrollment: 193 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• New onset moderate or severe cGVHD as defined by the 2014 National Institutes of Health (NIH) Consensus Development Project Criteria
• Need for systemic treatment with corticosteroids for cGVHD
• No previous systemic treatment for cGVHD (including extracorporeal photopheresis [ECP])
• Participants 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
• Age ≥12 years old
• Karnofsky or Lansky (subjects <16 years) performance status ≥60

Key Exclusion Criteria:

• Received any previous systemic treatment for cGVHD with the exception of corticosteroids administered for cGVHD within the 72 hours prior to signing the informed consent form.
• Inability to begin a prednisone dose ≥0.5 mg/kg/d for the treatment of cGVHD
• Any uncontrolled infection or active infection requiring ongoing systemic treatment
• Progressive underlying malignant disease or any post-transplant lymphoproliferative disease
• Known bleeding disorders
• Active hepatitis C virus (HCV) or hepatitis B virus (HBV)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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193 participants in 2 patient groups, including a placebo group

Ibrutinib + Prednisone

Experimental group

Description:

Ibrutinib (420 mg) given orally once daily continuously starting on Week 1 Day 1 until cGVHD progression, progression of underlying malignancy, participant begins another systemic treatment for cGVHD or unacceptable toxicity. The 420 mg dose was adjusted for cytochrome P450 \[CYP\] inhibitors or hepatic dysfunction as applicable. Prednisone 1 mg/kg/d given orally once daily continuously starting on Week 1 Day 1 until unacceptable toxicity or until participant is successfully tapered from the prednisone. Starting prednisone dose may be as low as 0.5 mg/kg/d if a participant cannot tolerate higher doses.

Treatment:

Drug: ibrutinib

Drug: Prednisone

Placebo + Prednisone

Placebo Comparator group

Description:

Placebo given orally once daily continuously starting on Week 1 Day 1 until cGVHD progression, progression of underlying malignancy, participant begins another systemic treatment for cGVHD or unacceptable toxicity. Prednisone 1 mg/kg/d given orally once daily continuously starting on Week 1 Day 1 until unacceptable toxicity or until participant is successfully tapered from the prednisone. Starting prednisone dose may be as low as 0.5 mg/kg/d if a participant cannot tolerate higher doses.

Treatment:

Drug: Prednisone

Drug: Placebo