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

NCT03151057 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: J1633IRB00157704
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  The evaluation of the safety of Idelalisib as post-transplantation maintenance in patients with B cell hematologic malignancies

  Day 90 - Day 270 post transplant

Secondary Outcomes (2)

• Event Free Survival at One Year.

  Beginning Day 90 post transplant until Day 360

• 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

Study Arms (2)

Idelalisib 100mg

EXPERIMENTAL

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

Drug: Idelalisib 100 MG

Placebo oral tablet

PLACEBO COMPARATOR

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

Drug: Placebo Oral Tablet

Interventions

Idelalisib 100 MG DRUG

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

Also known as: Zydelig

Idelalisib 100mg

Placebo Oral Tablet DRUG

placebo

Placebo oral tablet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>18 years of age
• 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).
• T bili ≤ 1.5 mg/dL except for patients with Gilbert's syndrome or hemolysis
• AST, ALT and alk phos all \< 2.5X ULN
• Karnofsky performance score ≥ 40
• ECOG ≤3
• 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.
• 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.
• Ability to receive oral medication.
• Ability to understand and provide informed consent.

You may not qualify if:

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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Gilead Sciences: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21205, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Disease

Interventions

idelalisib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma

Results Point of Contact

• Title: Dr. Douglas Gladstone
• Organization: Northwell Health Cancer Institute

msteve35@jhmi.edu

(516) 734-8900

Study Officials

• Douglas Gladstone, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participant, investigator
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Idelalisib 100mg or placebo twice daily, starting day +90 (+-/ 10 days) after transplant until day +270.

Study Record Dates

• First Submitted: March 29, 2017
• First Posted: May 12, 2017
• Study Start: July 31, 2018
• Primary Completion: June 20, 2022
• Study Completion: July 20, 2022
• Last Updated: March 12, 2024
• Results First Posted: March 12, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)