Platform Study for the Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma (PRISM Study)
PRISM
PRISM: A Platform Protocol for the Treatment of Relapsed/Refractory Aggressive Non-Hodgkin's Lymphoma
4 other identifiers
interventional
30
2 countries
12
Brief Summary
This is a Phase 1 platform protocol designed to evaluate various targeted agents for the treatment of relapsed/refractory aggressive Non-Hodgkin's Lymphoma (NHL).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jun 2018
Typical duration for phase_1
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 24, 2018
CompletedFirst Posted
Study publicly available on registry
May 17, 2018
CompletedStudy Start
First participant enrolled
June 19, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
March 31, 2021
CompletedAugust 15, 2022
August 1, 2022
2.8 years
April 24, 2018
August 11, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Safety of the study treatments when given in combination [Incidence of adverse events]
Incidence of adverse events
Through to study completion, an average of 1 year
Secondary Outcomes (13)
Assessment of the efficacy of each treatment by evaluation of overall response rate using RECIL 2017 response criteria
Through to study completion, an average of 1 year
Duration of response (DOR) using RECIL 2017 response criteria for the anti-tumour activity of each therapy.
Through to study completion, an average of 1 year
Progression free survival (PFS) using RECIL 2017 response criteria for the anti-tumour activity of each therapy.
Through to study completion, an average of 1 year
Overall Survival (OS)
From the beginning of treatment until the date of death from any cause, assessed up to 12 months
Peak plasma concentration (Cmax) of Study Drug A (Arm 1)
Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only; then predose and approximately 1 hr (end of infusion of Study Drug A) on Day 1 of every odd cycle starting with Cycle 3 through study completion, an average of 1 year
- +8 more secondary outcomes
Study Arms (4)
AZD9150 + Acalabrutinib
EXPERIMENTALAZD9150 given in combination with acalabrutinib
AZD6738 + Acalabrutinib
EXPERIMENTALAZD6738 in combination with acalabrutinib
Hu5F9-G4 + rituximab + Acalabrutinib
EXPERIMENTALHu5F9-G4/rituximab in combination with acalabrutinib
AZD5153 + Acalabrutinib
EXPERIMENTALAZD5153 in combination with acalabrutinib
Interventions
AZD9150 will be administered as a 1-hour intravenous (IV) infusion on Days 1, 3, 5 of Cycle 1, followed by weekly infusions (starting Day 8 of Cycle 1 and beyond).
Acalabrutinib will be administered orally twice daily (bid).
AZD6738 will be administered orally twice daily (bid).
HU5F9-G4 infusions will be given on Weekly (Day 1, 8, 15, and 22) during the first two 28-day cycles, then will be given every two weeks (Day 1 and Day 15) in Cycle 3 and beyond.
Rituximab infusions will be given Weekly starting on Day 8 (Day 8, 15, and 22) during the first 28-day cycle (4 weeks), then Day 1 of each 4 week cycle for Cycles 2-6. Starting with Cycle 8, Rituximab will be infused on Day 1 of every other cycle (every 8 weeks).
AZD5153 will be administered orally once per day (qd).
Eligibility Criteria
You may qualify if:
- Diagnosis of relapsed/refractory aggressive Non Hodgkin's Lymphoma (NHL) with histology based on established World Health Organization (WHO) criteria.
- Must have received ≥1 prior line of therapy for the treatment of current histology, there are no known curative treatment options available, or subject ineligible for potential curative options.
- Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy. Not applicable for cutaneous lesions.
- ECOG performance status of ≤2.
- \. Must have previously received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone or equivalent regimen with stem-cell rescue. Or who are ineligible for highdose chemotherapy with stem-cell rescue and/or chimeric antigen receptor (CAR) T cell therapy.
- Ineligibility for high-dose therapy with stem cell rescue and/or CAR T-cell therapy will be determined by the investigator.
- \. Must have previously received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone or equivalent regimen with stem-cell rescue. Or who are ineligible for highdose chemotherapy with stem-cell rescue and/or chimeric antigen receptor (CAR) T-cell therapy.
- Ineligibility for high-dose therapy with stem cell rescue and/or CAR T-cell therapy will be determined by the investigator.
- \. Must have previously received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone or equivalent regimen with stem-cell rescue. Or who are ineligible for highdose chemotherapy with stem-cell rescue and/or chimeric antigen receptor (CAR) T cell therapy.
- Ineligibility for high-dose therapy with stem cell rescue and/or CAR T-cell therapy will be determined by the investigator.
- \. Must have previously received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone or equivalent regimen with stem-cell rescue. Or who are ineligible for highdose chemotherapy with stem-cell rescue and/or chimeric antigen receptor (CAR) T cell therapy.
- Ineligibility for high-dose therapy with stem cell rescue and/or CAR T-cell therapy will be determined by the investigator.
You may not qualify if:
- History of prior malignancy except for the following: a) Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening and felt to be at low risk for recurrence by treating physician, b) Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer, c) Adequately treated carcinoma in situ without current evidence of disease, d) Evidence of severe or uncontrolled systemic disease, or current unstable or uncompensated respiratory or cardiac conditions, or uncontrolled hypertension, history of, or active, bleeding diatheses or uncontrolled active systemic fungal, bacterial, viral, or other infection, or intravenous anti-infective treatment within 2 weeks before first dose of study treatment.
- Serologic status reflecting active hepatitis B or C infection.
- Prior use of standard antilymphoma therapy or radiation therapy within 14 days of receiving the first dose of study treatment (not including palliative radiotherapy or palliative corticosteroid use).
- Requires ongoing immunosuppressive therapy, including systemic corticosteroids for treatment of lymphoid cancer or other conditions.
- For subjects under DLT review only: Any haematopoietic growth factors or darbepoetin within 14 days of the first dose of study treatment.
- Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.
- Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal (GI) function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- Requires treatment with proton-pump inhibitors.
- Requires treatment with strong CYP3A inhibitors or inducers.
- Relative hypotension (\< 90/60 mm Hg) or clinically relevant orthostatic hypotension, including a fall in blood pressure of \>20 mm Hg.
- Uncontrolled hypertension requiring clinical intervention.
- At risk for brain perfusion problems based on medical history.
- Mean resting QT interval (QTc) calculated using Fridericia's formula (QTcF) \>470 msec for female subjects and \>450 msec for male subjects obtained from 3 electrocardiograms (ECGs), or congenital long QT syndrome.
- Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.
- Known to have tested positive for human immunodeficiency virus (HIV) \& requires treatment with restricted medications.
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Acerta Pharma BVlead
- AstraZenecacollaborator
Study Sites (12)
Research Site
Los Angeles, California, 90095, United States
Research Site
Sarasota, Florida, 34232, United States
Research Site
Atlanta, Georgia, 30322, United States
Research Site
New Orleans, Louisiana, 70112, United States
Research Site
Bethesda, Maryland, 20892, United States
Research Site
Omaha, Nebraska, 68198, United States
Research Site
Rochester, New York, 14642, United States
Research Site
Nashville, Tennessee, 37203, United States
Research Site
Charlottesville, Virginia, 22908, United States
Research Site
Seattle, Washington, 98104, United States
Research Site
London, W1G 6AD, United Kingdom
Research Site
Oxford, OX3 7EJ, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Ian Flinn, MD, PhD
Tennessee Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 24, 2018
First Posted
May 17, 2018
Study Start
June 19, 2018
Primary Completion
March 31, 2021
Study Completion
March 31, 2021
Last Updated
August 15, 2022
Record last verified: 2022-08
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.