Idelalisib Post Allogeneic Hematopoietic Stem Cell Transplant (HSCT) in B Cell Derived Malignancies
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|ClinicalTrials.gov Identifier: NCT03151057|
Recruitment Status : Terminated (Safety endpointreached)
First Posted : May 12, 2017
Last Update Posted : November 10, 2022
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|Condition or disease||Intervention/treatment||Phase|
|B Cells-Tumors B Cell Chronic Lymphocytic Leukemia Follicular Lymphoma Mantle Cell Lymphoma Large B-Cell Diffuse Lymphoma of Bone (Diagnosis)||Drug: Idelalisib 100 MG Drug: Placebo Oral Tablet||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Idelalisib 100mg or placebo twice daily, starting day +90 (+-/ 10 days) after transplant until day +270.|
|Masking:||Double (Participant, Investigator)|
|Masking Description:||Participant, investigator|
|Official Title:||Idelalisib Post Allogeneic Hematopoietic Stem Cell Transplant (HSCT) in B Cell Derived Malignancies: A Phase 1 Double Blinded Randomized Placebo Toxicity Trial|
|Actual Study Start Date :||July 31, 2018|
|Actual Primary Completion Date :||June 20, 2022|
|Actual Study Completion Date :||July 20, 2022|
Experimental: 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
Drug: Idelalisib 100 MG
100mg BID beginning on day 90 (+/- 10days) and continuing until day 270 post transplant.
Other Name: Zydelig
Placebo Comparator: Placebo oral tablet
Placebo to be taken twice daily beginning +90(+/- 10) days after allo HSCT and continued through Day 270 post transplant
Drug: Placebo Oral Tablet
- 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. [ Time Frame: Day 90 - Day 270 post transplant ]The evaluation of the safety of Idelalisib as post-transplantation maintenance in patients with B cell hematologic malignancies
- Event free survival at one year. [ Time Frame: Beginning Day 90 post transplant until Day 360 ]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 [ Time Frame: Beginning Day 90 post transplant until Day 270 ]Search for Biomarkers which could better identify which patients would respond to treatment with Idelalisib in the post-transplant setting.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- >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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03151057
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21205|
|Principal Investigator:||Douglas Gladstone, MD||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
Documents provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
|Responsible Party:||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Other Study ID Numbers:||
IRB00157704 ( Other Identifier: JHMIRB )
|First Posted:||May 12, 2017 Key Record Dates|
|Last Update Posted:||November 10, 2022|
|Last Verified:||November 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
post transplant maintenance therapy
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Immune System Diseases
Molecular Mechanisms of Pharmacological Action