Clinical trial NCT03151057: Idelalisib Post Allogeneic Hematopoietic Stem Cell Transplant (HSCT) in B Cell Derived Malignancies
Official title: Idelalisib Post Allogeneic Hematopoietic Stem Cell Transplant (HSCT) in B Cell Derived Malignancies: A Phase 1 Double Blinded Randomized Placebo Toxicity Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: B Cells-Tumors
B Cell Chronic Lymphocytic Leukemia
Follicular Lymphoma
Mantle Cell Lymphoma
Large B-Cell Diffuse Lymphoma of Bone (Diagnosis)
Keywords: Idelalisib
Zydelig
allo transplant
PI3K inhibitor
post transplant maintenance therapy
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2017-05-12
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Idelalisib 100mg or placebo twice daily, starting day +90 (+-/ 10 days) after transplant until day +270.
Primary purpose: TREATMENT

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.

Eligibility criteria: INCLUSION CRITERIA

1. \>18 years of age
2. Has undergone allo HSCT to treat a B-cell derived hematologic malignancy: accepted alloHSCT regimens include: myeloablative or reduced intensity conditioning from any donor (matched, partially mismatched or cord) and any source (peripheral blood, bone marrow, or cord).
3. T bili ≤ 1.5 mg/dL except for patients with Gilbert's syndrome or hemolysis
4. AST, ALT and alk phos all \< 2.5X ULN
5. Karnofsky performance score ≥ 40
6. ECOG ≤3
7. For women of childbearing potential, a negative serum or urine pregnancy test with sensitivity less than 50 mIU/m within 72 hours before the start of study medication.
8. Use of two forms of contraception with less than a 5% failure rate or abstinence by all transplanted patients for a minimum of 1 month after the last dose of Idelalisib. For the first 60 days post-transplant, transplant recipients should be encouraged to use non-hormonal contraceptives due to the potential adverse effect of hormones on bone marrow engraftment.
9. Ability to receive oral medication.
10. Ability to understand and provide informed consent.

EXCLUSION CRITERIA

1. ECOG \>3 (Karnofsky \<40%)
2. ALT, AST \>2.5 ULN or total bilirubin \>1.5 ULN (not attributable to Gilbert's)
3. Women who are pregnant or breastfeeding.
4. Exclude if patient has cirrhosis or is currently being actively treated for hepatitis C.
5. History of positive HIV-1 or HIV-2 serologies or nucleic acid test.
6. Active hepatitis B infection as documented by positive Hepatitis B PCR assay
7. Use of investigational drug, other than the study medications specified by the protocol, within 30 days of transplantation.
8. Receipt of a live vaccine within 30 days of receipt of study therapy.
9. ≥ Grade II aGVHD
10. The presence of any medical condition that the Investigator deems incompatible with participation in the trial
11. Subjects who are required to use a medication classified as a strong CYP3A inducer of inhibitor.

Primary outcomes:
measure: 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.
timeFrame: Day 90 - Day 270 post transplant
Secondary outcomes:
measure: Event Free Survival at One Year.
timeFrame: Beginning Day 90 post transplant until Day 360
measure: 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
timeFrame: Beginning Day 90 post transplant until Day 270
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Douglas Gladstone, MD
role: PRINCIPAL_INVESTIGATOR
References: