Clinical Trials /

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

NCT03527147

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).

Related Conditions:
  • Aggressive Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Platform Study for the Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma (PRISM Study)
  • Official Title: PRISM: A Platform Protocol for the Treatment of Relapsed/Refractory Aggressive Non-Hodgkin's Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: ACE-LY-111
  • SECONDARY ID: 2017-004191-63
  • SECONDARY ID: D9820C00001
  • SECONDARY ID: LYM 138
  • NCT ID: NCT03527147

Conditions

  • NHL
  • DLBCL
  • Non-hodgkin's Lymphoma
  • Diffuse Large B Cell Lymphoma

Interventions

DrugSynonymsArms
AZD9150STAT3 inhibitorAZD9150 + Acalabrutinib
AcalabrutinibCALQUENCE®, ACP-196AZD9150 + Acalabrutinib
AZD6738ATR inhibitorAZD6738 + Acalabrutinib
Hu5F9-G4anti-CD47 antibodyHu5F9-G4 + rituximab + Acalabrutinib
RituximabRITUXAN®Hu5F9-G4 + rituximab + Acalabrutinib
AZD5153BRD4 inhibitorAZD5153 + Acalabrutinib

Purpose

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).

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.
    

Trial Arms

NameTypeDescriptionInterventions
AZD9150 + AcalabrutinibExperimentalAZD9150 given in combination with acalabrutinib
  • AZD9150
  • Acalabrutinib
AZD6738 + AcalabrutinibExperimentalAZD6738 in combination with acalabrutinib
  • Acalabrutinib
  • AZD6738
Hu5F9-G4 + rituximab + AcalabrutinibExperimentalHu5F9-G4/rituximab in combination with acalabrutinib
  • Acalabrutinib
  • Hu5F9-G4
  • Rituximab
AZD5153 + AcalabrutinibExperimentalAZD5153 in combination with acalabrutinib
  • Acalabrutinib
  • AZD5153

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

Primary Outcome Measures

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
Safety Issue:
Description:Incidence of adverse events

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Acerta Pharma BV

Trial Keywords

  • Acalabrutinib
  • CALQUENCE®
  • ACP-196
  • Platform study
  • Master protocol
  • PRISM
  • Hu-5F9
  • Rituximab
  • ATR
  • STAT3
  • Anti-CD47
  • BRD4

Last Updated

August 21, 2019