Back to results

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

Primary Purpose

B Cells-Tumors, B Cell Chronic Lymphocytic Leukemia, Follicular Lymphoma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Idelalisib 100 MG

Placebo Oral Tablet

About this trial

This is an interventional treatment trial for B Cells-Tumors focused on measuring Idelalisib, Zydelig, allo transplant, PI3K inhibitor, post transplant maintenance therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA

>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.

EXCLUSION CRITERIA

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.

Sites / Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Idelalisib 100mg

Placebo oral tablet

Arm 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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Event free survival at one year.

Impact of Idelalisib on aGVHD, relapse, and non-relapse mortality

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

Search for Biomarkers which could better identify which patients would respond to treatment with Idelalisib in the post-transplant setting.

Full Information

NCT ID

NCT03151057

First Posted

March 29, 2017

Last Updated

November 7, 2022

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

Gilead Sciences

1. Study Identification

Unique Protocol Identification Number

NCT03151057

Brief Title

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

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Terminated

Why Stopped

Safety endpointreached

Study Start Date

July 31, 2018 (Actual)

Primary Completion Date

June 20, 2022 (Actual)

Study Completion Date

July 20, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

ParticipantInvestigator

Masking Description

Participant, investigator

Allocation

Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Idelalisib 100mg

Arm Type

Experimental

Arm Description

Arm Title

Placebo oral tablet

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Idelalisib 100 MG

Other Intervention Name(s)

Zydelig

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo Oral Tablet

Intervention Description

placebo

Primary Outcome Measure Information:

Title

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.

Description

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

Time Frame

Day 90 - Day 270 post transplant

Secondary Outcome Measure Information:

Title

Event free survival at one year.

Description

Impact of Idelalisib on aGVHD, relapse, and non-relapse mortality

Time Frame

Beginning Day 90 post transplant until Day 360

Title

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

Description

Search for Biomarkers which could better identify which patients would respond to treatment with Idelalisib in the post-transplant setting.

Time Frame

Beginning Day 90 post transplant until Day 270

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

INCLUSION CRITERIA >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. EXCLUSION CRITERIA 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Douglas Gladstone, MD

Organizational Affiliation

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21205

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs