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

NCT ID: NCT03151057

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-31
• Study Completion Date: 2022-07-20

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Idelalisib 100mg

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

Group Type: EXPERIMENTAL

Idelalisib 100 MG

Intervention Type: DRUG

100mg BID beginning on day 90 (+/- 10days) and continuing until day 270 post transplant.

Placebo oral tablet

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

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

placebo

Interventions

Idelalisib 100 MG

100mg BID beginning on day 90 (+/- 10days) and continuing until day 270 post transplant.

Intervention Type: DRUG

Placebo Oral Tablet

placebo

Intervention Type: DRUG

Other Intervention Names

Zydelig

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Douglas Gladstone, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00157704

Identifier Type: OTHER

Identifier Source: secondary_id

J1633

Identifier Type: -

Identifier Source: org_study_id