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).

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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 names:
    • 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 names:
    • 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 names:
    • 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 names:
    • 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 names:
    • BRD4 inhibitor

Recruiting Locations

Tulane Cancer Center
New Orleans, Louisiana 70112
Contact:
Acerta Pharma Clinical Trials

More Details

NCT ID
NCT03527147
Status
Recruiting
Sponsor
Acerta Pharma BV

Study Contact

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

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.