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

Johns Hopkins Medicine

Status and phase: Terminated; Phase 1

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

Treatments: Drug: Placebo Oral Tablet; Drug: Idelalisib 100 MG

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03151057

J1633

IRB00157704 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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16 participants in 2 patient groups, including a placebo group

Idelalisib 100mg

Experimental group

Description:

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

Treatment:

Drug: Idelalisib 100 MG

Placebo oral tablet

Placebo Comparator group

Description:

Placebo to be taken twice daily beginning +90(+/- 10) days after allo HSCT and continued through Day 270 post transplant

Treatment:

Drug: Placebo Oral Tablet