Idelalisib Post Allogeneic Hematopoietic Stem Cell Transplant (HSCT) in B Cell Derived Malignancies

Phase 1

Terminated

Conditions: B Cells-Tumors
Mantle Cell Lymphoma
Large B-Cell Diffuse Lymphoma of Bone (Diagnosis)
B Cell Chronic Lymphocytic Leukemia
Follicular Lymphoma

Brief Summary: This is a study to evaluate the safety of idelalisib as post-transplantation maintenance in patients with B cell hematologic malignancies undergoing a allogeneic hematopoietic stem cell transplant (HSCT). Safety will be evaluated through the assessment of cytopenias, effect on donor chimerism, effect on the incidence and severity of acute graft versus host disease, and gastro-intestinal tolerance.

Detailed Description: Currently, to improve overall survival, the focus of the BMT program at JHH the introduction of anti-neoplastic therapy post transplantation: where the allo BMT serves as a platform to allowing a new intolerant immune system to interact with the post allo BMT intervention.

The importance of post BMT therapy has been made evident with tyrosine kinase inhibition (TKI) in Philadelphia chromosome positive acute lymphocytic leukemia (ALL) and chronic myeloid leukemia(CML), where patients who had disease progression while on TKI therapy pre-allo BMT enjoy marked improvement in overall survival when TKI is part of a maintenance program; the use of DNA hypomethylation agents after allo BMT for relapsed myeloid malignances; or the use of rituximab after allo BMT in follicular lymphoma.

Idelalisib, an orally-administered, selective inhibitor of Phosphoinositide 3 kinase (PI3K), is extremely effective in inducing partial responses to complete responses in many B-cell derived malignancies and should be studied in the post alloHSCT setting. Johns Hopkins Hospital has one of the world's largest experiences with alloHSCT. This study proposes a double blinded randomized phase I placebo trial where all patients who have undergone alloHSCT for a B-cell derived hematologic malignancy be offered either idelalisib 100mg or placebo twice daily for 180 days starting approximately 90 days after their HSCT.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Idelalisib 100mg	Idelalisib 100 MG	Idelalisib is an orally-administered, selective inhibitor of Phosphoinositide 3 kinase (PI3K)-delta which has been shown to be extremely effective in inducing partial to complete responses in many B-cell derived malignancies. intervention: 100mg Idelalisib twice daily beginning +90(+/- 10) days after allo HSCT and continued through Day 270 post transplant
Placebo oral tablet	Placebo Oral Tablet	Placebo to be taken twice daily beginning +90(+/- 10) days after allo HSCT and continued through Day 270 post transplant

Primary Outcome Measures

Name	Time	Method
Treatment-limiting Toxicities Will be Defined as Idelalisib Interruption for >14 Days, or Other >3 Adverse Events as Defined by CTCAE IV Not Captured in the Protocol for Dose De-escalation.	Day 90 - Day 270 post transplant	The evaluation of the safety of Idelalisib as post-transplantation maintenance in patients with B cell hematologic malignancies

Secondary Outcome Measures

Name	Time	Method
Identify Potential Predictive Biomarker Candidates Based on Exploratory Gene Expression Analysis of Immune Biomarkers in Bone Marrow Aspirates and Whole or Targeted Exome Sequencing of Lymphoma Cells	Beginning Day 90 post transplant until Day 270	Search for Biomarkers which could better identify which patients would respond to treatment with Idelalisib in the post-transplant setting.
Event Free Survival at One Year.	Beginning Day 90 post transplant until Day 360	Impact of Idelalisib on aGVHD, relapse, and non-relapse mortality