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

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: NCT03527147
Recruitment Status : Recruiting
First Posted : May 17, 2018
Last Update Posted : August 26, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Acerta Pharma BV

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).

Condition or disease Intervention/treatment Phase
NHL DLBCL Non-hodgkin's Lymphoma Diffuse Large B Cell Lymphoma Drug: AZD9150 Drug: Acalabrutinib Drug: AZD6738 Drug: Hu5F9-G4 Drug: Rituximab Drug: AZD5153 Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 88 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: PRISM: A Platform Protocol for the Treatment of Relapsed/Refractory Aggressive Non-Hodgkin's Lymphoma
Actual Study Start Date : June 19, 2018
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: AZD9150 + Acalabrutinib
AZD9150 given in combination with acalabrutinib
Drug: AZD9150
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).
Other Name: STAT3 inhibitor

Drug: Acalabrutinib
Acalabrutinib will be administered orally twice daily (bid).
Other Names:
  • CALQUENCE®
  • ACP-196

Experimental: AZD6738 + Acalabrutinib
AZD6738 in combination with acalabrutinib
Drug: Acalabrutinib
Acalabrutinib will be administered orally twice daily (bid).
Other Names:
  • CALQUENCE®
  • ACP-196

Drug: AZD6738
AZD6738 will be administered orally twice daily (bid).
Other Name: ATR inhibitor

Experimental: Hu5F9-G4 + rituximab + Acalabrutinib
Hu5F9-G4/rituximab in combination with acalabrutinib
Drug: Acalabrutinib
Acalabrutinib will be administered orally twice daily (bid).
Other Names:
  • CALQUENCE®
  • ACP-196

Drug: Hu5F9-G4
Hu5F9-G4 infusions will be administered weekly.
Other Name: anti-CD47 antibody

Drug: Rituximab
Rituximab infusions will be administered weekly for one cycle (28 days) and then every 4 weeks up to 6 cycles.
Other Name: RITUXAN®

Experimental: AZD5153 + Acalabrutinib
AZD5153 in combination with acalabrutinib
Drug: Acalabrutinib
Acalabrutinib will be administered orally twice daily (bid).
Other Names:
  • CALQUENCE®
  • ACP-196

Drug: AZD5153
AZD5153 will be administered orally once per day (qd).
Other Name: BRD4 inhibitor




Primary Outcome Measures :
  1. Safety of the study treatments when given in combination [Incidence of adverse events] [ Time Frame: Through to study completion, an average of 1 year ]
    Incidence of adverse events


Secondary Outcome Measures :
  1. Assessment of the efficacy of each treatment by evaluation of overall response rate using RECIL 2017 response criteria [ Time Frame: Through to study completion, an average of 1 year ]
    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.

  2. Duration of response (DOR) using RECIL 2017 response criteria for the anti-tumour activity of each therapy. [ Time Frame: Through to study completion, an average of 1 year ]
    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.

  3. Progression free survival (PFS) using RECIL 2017 response criteria for the anti-tumour activity of each therapy. [ Time Frame: Through to study completion, an average of 1 year ]
    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.

  4. Overall Survival (OS) [ Time Frame: From the beginning of treatment until the date of death from any cause, assessed up to 12 months ]
    Overall Survival (OS) is defined as the time from first dose until the date of death from any cause.

  5. Peak plasma concentration (Cmax) of Study Drug A (Arm 1) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 ]


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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Inclusion Criteria For All Arms:

  1. Diagnosis of relapsed/refractory aggressive Non Hodgkin's Lymphoma (NHL) with histology based on established World Health Organization (WHO) criteria.
  2. 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.
  3. Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy. Not applicable for cutaneous lesions.
  4. ECOG performance status of ≤2.

Inclusion Criteria for Arm 1:

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.

Inclusion Criteria for Arm 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.

Inclusion Criteria for Arm 3:

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.

Inclusion Criteria for Arm 4:

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.

Exclusion Criteria:

Exclusion Criteria For All Arms:

  1. 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.
  2. Serologic status reflecting active hepatitis B or C infection.
  3. 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).
  4. Requires ongoing immunosuppressive therapy, including systemic corticosteroids for treatment of lymphoid cancer or other conditions.
  5. For subjects under DLT review only: Any haematopoietic growth factors or darbepoetin within 14 days of the first dose of study treatment.

Exclusion Criteria for Arm 1:

  1. Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.
  2. 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.
  3. Requires treatment with proton-pump inhibitors.
  4. Requires treatment with strong CYP3A inhibitors or inducers.

Exclusion Criteria for Arm 2:

  1. Relative hypotension (< 90/60 mm Hg) or clinically relevant orthostatic hypotension, including a fall in blood pressure of >20 mm Hg.
  2. Uncontrolled hypertension requiring clinical intervention.
  3. At risk for brain perfusion problems based on medical history.
  4. 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.
  5. Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.
  6. Known to have tested positive for human immunodeficiency virus (HIV) & requires treatment with restricted medications.
  7. 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.
  8. Requires treatment with proton-pump inhibitors.

Exclusion Criteria for Arm 3:

  1. Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.
  2. 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.
  3. Requires treatment with proton-pump inhibitors.
  4. Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of RBC transfusions during the 4-week period prior to screening.
  5. History of haemolytic anaemia or Evans syndrome in the last 3 months before enrolment.
  6. Positive IgG component of the direct antiglobulin test (DAT).
  7. Prior treatment with CD47 or SIRPα-targeting agents.
  8. Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab

Exclusion Criteria for Arm 4:

  1. Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.
  2. 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.
  3. Requires treatment with proton-pump inhibitors.
  4. Requires treatment with CYP3A inhibitors or inducers or substrates of drug transporters.
  5. History of tuberculosis.
  6. Mean resting corrected QT interval (QTcF) >450 msec obtained from 3 electrocardiograms (ECGs); clinically important ECG findings, or risk factors for QTc prolongation.
  7. Subjects receiving antiplatelet or anticoagulant therapies within 28 days of first dose of study drug.

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): NCT03527147


Contacts
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Contact: Acerta Pharma Clinical Trials 1-888-292-9613 acertamc@dlss.com

Locations
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United States, California
UCLA Hematology Oncology Recruiting
Los Angeles, California, United States, 90095
Contact: Acerta Pharma Clinical Trials         
Contact    1-888-292-9613    acertamc@dlss.com   
United States, Florida
Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: Acerta Pharma Clinical Trials         
Contact    1-888-292-9613    acertamc@dlss.com   
United States, Georgia
Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
Contact: Acerta Pharma Clinical Trials         
Contact    1-888-292-9613    acertamc@dlss.com   
United States, Kentucky
Norton Cancer Institute Recruiting
Louisville, Kentucky, United States, 40207
Contact: Acerta Pharma Clinical Trials         
Contact    1-888-292-9613    acertamc@dlss.com   
United States, Louisiana
Tulane Cancer Center Recruiting
New Orleans, Louisiana, United States, 70112
Contact: Acerta Pharma Clinical Trials         
Contact    1-888-292-9613    acertamc@dlss.com   
United States, Maryland
National Cancer Institute Recruiting
Bethesda, Maryland, United States, 20892
Contact: Acerta Pharma Clinical Trials         
Contact    1-888-292-9613    acertamc@dlss.com   
United States, Nebraska
University of Nebraska Recruiting
Omaha, Nebraska, United States, 68198
Contact: Acerta Pharma Clinical Trials         
Contact    1-888-292-9613    acertamc@dlss.com   
United States, New York
University of Rochester Recruiting
Rochester, New York, United States, 14642
Contact: Acerta Pharma Clinical Trials         
Contact    1-888-292-9613    acertamc@dlss.com   
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Acerta Pharma Clinical Trials         
Contact    1-888-292-9613    acertamc@dlss.com   
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Acerta Pharma Clinical Trials         
Contact    1-888-292-9613    acertamc@dlss.com   
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98104
Contact: Acerta Pharma Clinical Trials         
Contact    1-888-292-9613    acertamc@dlss.com   
United Kingdom
Sarah Cannon Research Institute UK Recruiting
London, United Kingdom
Contact: Acerta Pharma Clinical Trials         
Contact    1-888-292-9613    acertamc@dlss.com   
Churchill Hospital Recruiting
Oxford, United Kingdom, OX3 7L3
Contact: Acerta Pharma Clinical Trials         
Contact    1-888-292-9613    acertamc@dlss.com   
Sponsors and Collaborators
Acerta Pharma BV
AstraZeneca
Investigators
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Study Chair: Ian Flinn, MD, PhD Tennessee Oncology

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Responsible Party: Acerta Pharma BV
ClinicalTrials.gov Identifier: NCT03527147     History of Changes
Other Study ID Numbers: ACE-LY-111
2017-004191-63 ( EudraCT Number )
D9820C00001 ( Other Identifier: AstraZeneca )
LYM 138 ( Other Identifier: Sarah Cannon Development Innovations )
First Posted: May 17, 2018    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Acerta Pharma BV:
Acalabrutinib
CALQUENCE®
ACP-196
Platform study
Master protocol
PRISM
Hu-5F9
Rituximab
ATR
STAT3
Anti-CD47
BRD4
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Rituximab
Hu5F9-G4
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents