Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03151057
Recruitment Status : Recruiting
First Posted : May 12, 2017
Last Update Posted : September 7, 2018
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

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

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
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
Primary Purpose: Treatment
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
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
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
placebo




Primary Outcome Measures :
  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. [ 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


Secondary Outcome Measures :
  1. 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

  2. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Laura Ackley, RN 410-502-0969 lackley1@jhmi.edu
Contact: Mary Amanda Stevens, MD 443-287-0180 msteve35@jhmi.edu

Locations
Layout table for location information
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21205
Contact: Douglas Gladstone, MD    410-955-8781    dgladst1@jhmi.edu   
Contact: Mary A Stevens, MD    443-287-0180    msteve35@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Gilead Sciences
Investigators
Layout table for investigator information
Principal Investigator: Douglas Gladstone, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03151057     History of Changes
Other Study ID Numbers: J1633
IRB00157704 ( Other Identifier: JHMIRB )
First Posted: May 12, 2017    Key Record Dates
Last Update Posted: September 7, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Idelalisib
Zydelig
allo transplant
PI3K inhibitor
post transplant maintenance therapy

Additional relevant MeSH terms:
Layout table for MeSH terms
Idelalisib
Lymphoma
Lymphoma, Follicular
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia
Leukemia, B-Cell
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action