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NHLPhase 1PRISMNCT03527147

Platform Study for the Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma (PRISM Study)

A Phase 1 study testing AZD9150, Acalabrutinib and AZD6738 in people with NHL and DLBCL, run by Acerta Pharma BV at 12 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 130 years
Conditions the study is for
NHL, DLBCL, Non-hodgkin's Lymphoma
What is being tested?
AZD9150, Acalabrutinib and AZD6738
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
12 sitesin 2 countries
Study dates
19 Jun 2018to 31 Mar 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 130 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 1. 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.
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  • 1. 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.
  • 1. 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.
  • 1. 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.

Who cannot join

  • 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.
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  • 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.
  • 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.
  • 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.
  • Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of RBC transfusions during the 4-week period prior to screening.
  • History of haemolytic anaemia or Evans syndrome in the last 3 months before enrolment.
  • Positive IgG component of the direct antiglobulin test (DAT).
  • Prior treatment with CD47 or SIRPα-targeting agents.
  • Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab
  • 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 CYP3A inhibitors or inducers or substrates of drug transporters.
  • History of tuberculosis.
  • Mean resting corrected QT interval (QTcF) >450 msec obtained from 3 electrocardiograms (ECGs); clinically important ECG findings, or risk factors for QTc prolongation.
  • Subjects receiving antiplatelet or anticoagulant therapies within 28 days of first dose of study drug.

Trial locations and contacts

12 sites in 2 countries.

12 sites in 2 countries

United States10 sites

  • Research Site

    Atlanta, Georgia, 30322

  • Research Site

    Bethesda, Maryland, 20892

  • Research Site

    Charlottesville, Virginia, 22908

  • Research Site

    Los Angeles, California, 90095

  • Research Site

    Nashville, Tennessee, 37203

  • Research Site

    New Orleans, Louisiana, 70112

  • Research Site

    Omaha, Nebraska, 68198

  • Research Site

    Rochester, New York, 14642

  • Research Site

    Sarasota, Florida, 34232

  • Research Site

    Seattle, Washington, 98104

Other trials in United States

United Kingdom2 sites

  • Research Site

    London, W1G 6AD

  • Research Site

    Oxford, OX3 7EJ

Other trials in United Kingdom

About this study

Official title: PRISM: A Platform Protocol for the Treatment of Relapsed/Refractory Aggressive Non-Hodgkin's Lymphoma

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).

Read the detailed description

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). Each study arm will be conducted in a predefined disease subset. All study arms are open label and allocation to each study arm will not be randomized.

As this master platform protocol has multiple study arms, subjects can be screened for several study arms at once. Likewise, a subject who ends participation in one study arm may be rescreened for participation in another (separate) study arm.

The primary objective of the study is to evaluate the safety of targeted agents for the treatment of relapsed/refractory aggressive Non-Hodgkin's Lymphoma (NHL). This protocol has a modular design, with the potential for future treatment arms to be added via protocol amendment.

Being tested
AZD9150, Acalabrutinib, AZD6738, Hu5F9-G4, Rituximab
Keywords
Acalabrutinib, CALQUENCE®, ACP-196, Platform study, Master protocol, PRISM, Hu-5F9, Rituximab, ATR, STAT3, Anti-CD47, BRD4
Medical subject headings
Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD9150Drug

    Also called STAT3 inhibitor

    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).

  • AcalabrutinibDrug

    Also called CALQUENCE®, ACP-196

    Acalabrutinib will be administered orally twice daily (bid).

  • AZD6738Drug

    Also called ATR inhibitor

    AZD6738 will be administered orally twice daily (bid).

  • Hu5F9-G4Drug

    Also called anti-CD47 antibody

    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.

  • RituximabDrug

    Also called RITUXAN®

    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).

  • AZD5153Drug

    Also called BRD4 inhibitor

    AZD5153 will be administered orally once per day (qd).

Study groups in NCT03527147
Study groupRoleWhat they receive
AZD9150 + AcalabrutinibExperimentalAZD9150 given in combination with acalabrutinib
Receives: Drug: AZD9150; Drug: Acalabrutinib
AZD6738 + AcalabrutinibExperimentalAZD6738 in combination with acalabrutinib
Receives: Drug: Acalabrutinib; Drug: AZD6738
Hu5F9-G4 + rituximab + AcalabrutinibExperimentalHu5F9-G4/rituximab in combination with acalabrutinib
Receives: Drug: Acalabrutinib; Drug: Hu5F9-G4; Drug: Rituximab
AZD5153 + AcalabrutinibExperimentalAZD5153 in combination with acalabrutinib
Receives: Drug: Acalabrutinib; Drug: AZD5153

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of the study treatments when given in combination [Incidence of adverse events]

    Incidence of adverse events

    Measured: Through to study completion, an average of 1 year

Secondary outcomes (13)

  1. Assessment of the efficacy of each treatment by evaluation of overall response rate using RECIL 2017 response criteria

    The overall response rate (ORR) is defined as the rate of subjects who achieve either a partial response (PR) or complete response (CR) as assessed by investigators before receiving any other anticancer therapy.

    Measured: Through to study completion, an average of 1 year

  2. Duration of response (DOR) using RECIL 2017 response criteria for the anti-tumour activity of each therapy.

    Duration of Response (DOR) is defined as the time from the first objective response of CR or PR to the time of documented disease progression or death due to any cause, whichever occurs first.

    Measured: Through to study completion, an average of 1 year

  3. Progression free survival (PFS) using RECIL 2017 response criteria for the anti-tumour activity of each therapy.

    Progression free survival (PFS) is defined as the time from first dose date to documented objective disease progression, or death from any cause, whichever occurs first. Disease progression will be determined by the investigators per standard response criteria as outlined in each respective study arm.

    Measured: Through to study completion, an average of 1 year

  4. Overall Survival (OS)

    Overall Survival (OS) is defined as the time from first dose until the date of death from any cause.

    Measured: From the beginning of treatment until the date of death from any cause, assessed up to 12 months

  5. Peak plasma concentration (Cmax) of Study Drug A (Arm 1)

    Measured: 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

  6. Peak plasma concentration (Cmax) of Study Drug B (Arm 2)

    Measured: Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1

  7. Area under the plasma concentration versus time curve (AUC) of Study Drug A (Arm 1)

    Measured: 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. Area under the plasma concentration versus time curve (AUC) of Study Drug B (Arm 2)

    Measured: Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1

  9. Presence of Anti-Drug Antibody (ADA) titres in subjects treated with Study Drug A

    Measured: Samples will be collected predose on Days 1 and 8 of Cycle 1 and predose on Day 1 of every odd cycle starting with Cycle 3

  10. Peak plasma concentration (Cmax) of acalabrutinib (Arm 1)

    Measured: Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only

  11. Area under the plasma concentration versus time curve (AUC) for acalabrutinib (Arm 1)

    Measured: Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only

  12. Peak plasma concentration (Cmax) of acalabrutinib (Arm 2)

    Measured: Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1

  13. Area under the plasma concentration versus time curve (AUC) for acalabrutinib (Arm 2)

    Measured: Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2018
  2. Study start19 Jun 2018
  3. Primary completion31 Mar 2021
  4. Study completion31 Mar 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03527147
Sponsor's protocol ID
ACE-LY-111
Other IDs
2017-004191-63, D9820C00001, LYM 138, 2017
Acronym
PRISM
Status last verified
Aug 2022
First submitted
24 Apr 2018
Last updated
15 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD9150, Acalabrutinib and AZD6738 in people with NHL and DLBCL, run by Acerta Pharma BV at 12 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of the study treatments when given in combination [Incidence of adverse events] (time frame: Through to study completion, an average of 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03527147.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2022.

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