Clinical Trials /

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

NCT03151057

Description:

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.

Related Conditions:
  • B-Cell Neoplasm
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT03151057

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: J1633
  • SECONDARY ID: IRB00157704
  • NCT ID: NCT03151057

Conditions

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

Interventions

DrugSynonymsArms
Idelalisib 100 MGZydeligIdelalisib 100mg
Placebo Oral TabletPlacebo oral tablet

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Idelalisib 100mgExperimentalIdelalisib 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
  • Idelalisib 100 MG
Placebo oral tabletPlacebo ComparatorPlacebo to be taken twice daily beginning +90(+/- 10) days after allo HSCT and continued through Day 270 post transplant
  • Placebo Oral Tablet

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.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:The evaluation of the safety of Idelalisib as post-transplantation maintenance in patients with B cell hematologic malignancies

Secondary Outcome Measures

Measure:Event free survival at one year.
Time Frame:Beginning Day 90 post transplant until Day 360
Safety Issue:
Description:Impact of Idelalisib on aGVHD, relapse, and non-relapse mortality
Measure: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
Safety Issue:
Description:Search for Biomarkers which could better identify which patients would respond to treatment with Idelalisib in the post-transplant setting.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • Idelalisib
  • Zydelig
  • allo transplant
  • PI3K inhibitor
  • post transplant maintenance therapy

Last Updated

March 5, 2021