Informations générales (source: ClinicalTrials.gov)
Durvalumab/Tremelimumab in Neoadjuvant and Adjuvant Setting in Patients With HCC Treated by by Percutaneous Ablation Procedure in Curative Intent: French Multicenter Phase 2 Therapeutic
Interventional
Phase 2
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
mars 2024
septembre 2028
14 septembre 2025
This project is a Phase 2 trial testing the safety and efficacy of treatment with
Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting in patients
with BCLC A HCC treated by by percutaneous ablation (PA) procedure in a curative intent.
DUMELEP is a Multicentre, Phase 2 trial
Eligible patients will receive consecutively:
1. 1 Durvalumab 1500 mg/Tremelimumab 300 mg infusion in a neoadjuvant setting
2. percutaneous ablation procedure in a curative attempt at Day 30
3. 11 monthly Durvalumab 1500 mg infusions.
4. Classical follow-up during an additional year (every 3 months)
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP Assistance publique - Hôpitaux de Paris | 13/12/2025 07:36:55 | Contacter | |||
| AP-HP - Hôpital Avicenne | |||||
| AP-HP - Hôpital Beaujon | |||||
| AP-HP - Hôpital Cochin | |||||
| AP-HP - Hôpital Henri Mondor-Albert Chenevier | |||||
| AP-HP - Hôpital La Pitié-Salpêtrière | |||||
| AP-HP - Hôpital Saint Antoine | |||||
| AP-HP - Hôpital Tenon | |||||
Critères
Tous
Inclusion criteria
- Male or female patients ≥ 18 years of age
- Histological or radiological diagnosis of HCC
- Patients with newly diagnosed or recurrent HCC (following a previous curative
procedure performed at least 6 months before inclusion) eligible for PA as assessed
by multidisciplinary board corresponding to BCLC A stage:
- Uninodular HCC ≥ 2 cm and ≤ 5 cm, no macroscopic vascular invasion
- Multinodular maximum 3 nodules ≤ 3 cm
- Body weight >30 kg
- Liver function status Child-Pugh Class A
- <<Eastern Cooperative Oncology Group (ECOG)>><<World Health Organisation (WHO)
performance status of 0 or 1
- Adequate bone marrow, liver and renal function as assessed by the following
laboratory tests:
- Total bilirubin ≤ 2 mg/dL
- Serum creatinine ≤ 1.5 x ULN
- Lipase ≤ 2 x ULN
- Prothrombine time-international normalized ratio (PT-INR) < 2.3 and PTT < 1.5
- Glomerular Filtration Rate (GFR) ≥ 30 mL/min/1.73 m2
- Life expectancy ≥ 3 months
- Women of childbearing potential (WOCBP) need to accept one effective method of
contraception until 3 months after the last infusion of durvalumab and avoid
pregnancy
- Patients affiliated to a Social Security System
- Written informed consent signed (patients must be free from tutelle, curatelle or
sauvegarde de justice)
- Haemoglobin ≥9.0 g/dL
- Absolute neutrophil count (ANC ≥1.0 × 109/L)
- Platelet count ≥75 × 109/L
- Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). (This will not
apply to patients with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or
hepatic pathology), who will be allowed only in consultation with their physician.)
- AST (SGOT) and ALT (SGPT) ≤5x ULN
- Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine clearance
CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour
urine collection for determination of creatinine clearance:
Males:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
Females:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
- Patient is willing and able to comply with the protocol for the duration of the
study including undergoing treatment and scheduled visits and examinations including
follow up.
- Patients must have a life expectancy of at least 12 weeks
- At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target
lesion (TL) at pre inclusion/inclusion. Tumor assessment by computed tomography (CT)
scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to
inclusion
- Patients infected with HCV must be managed according to international
recommendations
- Antiviral therapy in case of HBV active infection or inactive carriage
Non inclusion criteria
- Patients with contraindications to PA procedure (Pacemakers or patients who have a
history of cardiac arrhythmias or irregular heartbeats in case of IRE, ascites,
Coagulopathy, Ongoing infection)
- Patients with contraindication to contrast medium intravenous injection either
gadolinium or iodinate
- Prior liver transplantation
- Uncontrolled HCC defined by the absence of remission > 6months following resection
of percutaneous ablation at time of inclusion
- Prior systemic treatment for HCC, in particular agents targeting T-cell
costimulation or checkpoint pathways (including those targeting PD-1, PD-L1 or
PD-L2, CD137, or cytotoxic Tlymphocyte antigen [CTLA-4]).
- Patients with uncontrolled HBV infection and viral load above 100 IU/mL.
- Patients with large esophageal varices at risk of bleeding that are not being
treated with conventional medical intervention
- Past or concurrent history of neoplasm other than HCC, except for in situ carcinoma
of the cervix uteri and/or non-melanoma skin cancer and superficial bladder tumors.
Any cancer curatively treated > 3 years prior to study entry is permitted
- Major surgical procedure or significant traumatic injury within 28 days before
enrolment
- Congestive heart failure New York Heart Association (NYHA) ≥ class 2
- Unstable angina or myocardial infarction within the past 6 months before enrolment
- Grade 3 (severe) hypertension ≥180 and/or ≥110 mmHG (systolic and diastolic,
according to National Heart Foundation 2016)
- Patients with phaeochromocytoma
- Refractory ascites according to EASL guidelines definition (ascites that cannot be
mobilized or the early recurrence of which cannot be prevented because of a lack of
response to sodium restriction and diuretic treatment)
- Persistent proteinuria of NCI-CTCAE version 5.0 ≥ Grade 3
- Ongoing infection > Grade 2 according to NCI-CTCAE version 5.0.
- Patients with chronic hepatitis B or inactive carriers for HBV must be under
anti-HBV treatment
- Clinically significant bleeding NCI-CTCAE version 5.0 ≥ Grade 3 within 30 days
before enrolment
- Any psychological, familial, sociological, geographical or illness or medical
condition that could jeopardize the safety of the patient and/or his compliance with
the study protocol and follow-up procedure
- Known history of human immunodeficiency virus (HIV) infection
- Non-healing wound, ulcer or bone fracture
- Known hypersensitivity to the study drug or excipients in the formulation
- Any malabsorption condition
- Breast feeding
- Pregnancy
- Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy or 180 days after
the last dose of durvalumab and tremelimumab combination therapy.
- Participation in another clinical study with an investigational product during the
last 6 months
- Concurrent enrolment in another clinical study, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study
- Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria :
1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis
after consultation with the Study Physician.
2. Patients with irreversible toxicity not reasonably expected to be exacerbated
by treatment with durvalumab or tremelimumab may be included only after
consultation with the Study Physician.
- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone
replacement therapy) is acceptable. <<amend as required based on any combination studies
with other anticancer agents>>
- Major surgical procedure (as defined by the Investigator) within 28 days prior to
the first dose of IP. Note: Local surgery of isolated lesions for palliative intent
is acceptable.
- History of allogenic organ transplantation.
- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease,
rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to
this criterion:
1. Patients with vitiligo or alopecia
2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
3. Any chronic skin condition that does not require systemic therapy
4. Patients without active disease in the last 5 years may be included but only
after consultation with the study physician
5. Patients with celiac disease controlled by diet alone
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
situations that would limit compliance with study requirement, substantially
increase risk of incurring AEs or compromise the ability of the patient to give
written informed consent
- History of another primary malignancy except for :
1. Malignancy treated with curative intent and with no known active disease ≥5
years before the first dose of IP and of low potential risk for recurrence
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
3. Adequately treated carcinoma in situ without evidence of disease
- History of leptomeningeal carcinomatosis
- Study excludes patients with -brain metastases or spinal cord compression: Patients
with suspected brain metastases at screening should have an MRI (preferred) or CT
each preferably with IV contrast of the brain prior to study entry. Brain metastases
will not be recorded as RECIST Target Lesions at baseline if study allows patients
with brain metastases.
- Has untreated central nervous system (CNS) metastases and/or carcinomatous
meningitis identified either on the baseline brain imaging (RECIST)) for details on
the imaging modality) obtained during the screening period or identified prior to
signing the ICF. Patients whose brain metastases have been treated may participate
provided they show radiographic stability (defined as 2 brain images, both of which
are obtained after treatment to the brain metastases.
These imaging scans should both be obtained at least four weeks apart and show no
evidence of intracranial progression). In addition, any neurologic symptoms that
developed either as a result of the brain metastases or their treatment must have
resolved or be stable either, without the use of steroids, or are stable on a steroid
dose of ≤10mg/day of prednisone or its equivalent <<and anti-convulsants>> for at least
14 days prior to the start of treatment. Brain metastases will not be recorded as RECIST
Target Lesions at baseline.
- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms
calculated from 3 ECGs (within 15 minutes at 5 minutes apart)
- History of active primary immunodeficiency
- Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV
1/2 antibodies) or active tuberculosis infection (clinical evaluation that may
include clinical history, physical examination and radiographic findings, or
tuberculosis testing in line with local practice).
- Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and
up to 30 days after the last dose of IP.
- Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy or180 days after
the last dose of durvalumab and tremelimumab combination therapy.
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
- Prior randomisation or treatment in a previous durvalumab and/or tremelimumab
clinical study regardless of treatment arm assignment.
- Patients who have received prior anti-PD-1, anti-PD-L1 or anti-CTLA-4:
1. Must not have experienced a toxicity that led to permanent discontinuation of
prior immunotherapy.
2. All AEs while receiving prior immunotherapy must have completely resolved or
resolved to baseline prior to screening for this study.
3. Must not have experienced a ≥Grade 3 immune related AE or an immune related
neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE:
Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are
stably maintained on appropriate replacement therapy and are asymptomatic.
4. Must not have required the use of additional immunosuppression other than
corticosteroids for the management of an AE, not have experienced recurrence of
an AE if re-challenged, and not currently require maintenance doses of > 10 mg
prednisone or equivalent per day.
- Male or female patients ≥ 18 years of age
- Histological or radiological diagnosis of HCC
- Patients with newly diagnosed or recurrent HCC (following a previous curative
procedure performed at least 6 months before inclusion) eligible for PA as assessed
by multidisciplinary board corresponding to BCLC A stage:
- Uninodular HCC ≥ 2 cm and ≤ 5 cm, no macroscopic vascular invasion
- Multinodular maximum 3 nodules ≤ 3 cm
- Body weight >30 kg
- Liver function status Child-Pugh Class A
- <<Eastern Cooperative Oncology Group (ECOG)>><<World Health Organisation (WHO)
performance status of 0 or 1
- Adequate bone marrow, liver and renal function as assessed by the following
laboratory tests:
- Total bilirubin ≤ 2 mg/dL
- Serum creatinine ≤ 1.5 x ULN
- Lipase ≤ 2 x ULN
- Prothrombine time-international normalized ratio (PT-INR) < 2.3 and PTT < 1.5
- Glomerular Filtration Rate (GFR) ≥ 30 mL/min/1.73 m2
- Life expectancy ≥ 3 months
- Women of childbearing potential (WOCBP) need to accept one effective method of
contraception until 3 months after the last infusion of durvalumab and avoid
pregnancy
- Patients affiliated to a Social Security System
- Written informed consent signed (patients must be free from tutelle, curatelle or
sauvegarde de justice)
- Haemoglobin ≥9.0 g/dL
- Absolute neutrophil count (ANC ≥1.0 × 109/L)
- Platelet count ≥75 × 109/L
- Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). (This will not
apply to patients with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or
hepatic pathology), who will be allowed only in consultation with their physician.)
- AST (SGOT) and ALT (SGPT) ≤5x ULN
- Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine clearance
CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour
urine collection for determination of creatinine clearance:
Males:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
Females:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
- Patient is willing and able to comply with the protocol for the duration of the
study including undergoing treatment and scheduled visits and examinations including
follow up.
- Patients must have a life expectancy of at least 12 weeks
- At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target
lesion (TL) at pre inclusion/inclusion. Tumor assessment by computed tomography (CT)
scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to
inclusion
- Patients infected with HCV must be managed according to international
recommendations
- Antiviral therapy in case of HBV active infection or inactive carriage
Non inclusion criteria
- Patients with contraindications to PA procedure (Pacemakers or patients who have a
history of cardiac arrhythmias or irregular heartbeats in case of IRE, ascites,
Coagulopathy, Ongoing infection)
- Patients with contraindication to contrast medium intravenous injection either
gadolinium or iodinate
- Prior liver transplantation
- Uncontrolled HCC defined by the absence of remission > 6months following resection
of percutaneous ablation at time of inclusion
- Prior systemic treatment for HCC, in particular agents targeting T-cell
costimulation or checkpoint pathways (including those targeting PD-1, PD-L1 or
PD-L2, CD137, or cytotoxic Tlymphocyte antigen [CTLA-4]).
- Patients with uncontrolled HBV infection and viral load above 100 IU/mL.
- Patients with large esophageal varices at risk of bleeding that are not being
treated with conventional medical intervention
- Past or concurrent history of neoplasm other than HCC, except for in situ carcinoma
of the cervix uteri and/or non-melanoma skin cancer and superficial bladder tumors.
Any cancer curatively treated > 3 years prior to study entry is permitted
- Major surgical procedure or significant traumatic injury within 28 days before
enrolment
- Congestive heart failure New York Heart Association (NYHA) ≥ class 2
- Unstable angina or myocardial infarction within the past 6 months before enrolment
- Grade 3 (severe) hypertension ≥180 and/or ≥110 mmHG (systolic and diastolic,
according to National Heart Foundation 2016)
- Patients with phaeochromocytoma
- Refractory ascites according to EASL guidelines definition (ascites that cannot be
mobilized or the early recurrence of which cannot be prevented because of a lack of
response to sodium restriction and diuretic treatment)
- Persistent proteinuria of NCI-CTCAE version 5.0 ≥ Grade 3
- Ongoing infection > Grade 2 according to NCI-CTCAE version 5.0.
- Patients with chronic hepatitis B or inactive carriers for HBV must be under
anti-HBV treatment
- Clinically significant bleeding NCI-CTCAE version 5.0 ≥ Grade 3 within 30 days
before enrolment
- Any psychological, familial, sociological, geographical or illness or medical
condition that could jeopardize the safety of the patient and/or his compliance with
the study protocol and follow-up procedure
- Known history of human immunodeficiency virus (HIV) infection
- Non-healing wound, ulcer or bone fracture
- Known hypersensitivity to the study drug or excipients in the formulation
- Any malabsorption condition
- Breast feeding
- Pregnancy
- Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy or 180 days after
the last dose of durvalumab and tremelimumab combination therapy.
- Participation in another clinical study with an investigational product during the
last 6 months
- Concurrent enrolment in another clinical study, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study
- Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria :
1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis
after consultation with the Study Physician.
2. Patients with irreversible toxicity not reasonably expected to be exacerbated
by treatment with durvalumab or tremelimumab may be included only after
consultation with the Study Physician.
- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone
replacement therapy) is acceptable. <<amend as required based on any combination studies
with other anticancer agents>>
- Major surgical procedure (as defined by the Investigator) within 28 days prior to
the first dose of IP. Note: Local surgery of isolated lesions for palliative intent
is acceptable.
- History of allogenic organ transplantation.
- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease,
rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to
this criterion:
1. Patients with vitiligo or alopecia
2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
3. Any chronic skin condition that does not require systemic therapy
4. Patients without active disease in the last 5 years may be included but only
after consultation with the study physician
5. Patients with celiac disease controlled by diet alone
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
situations that would limit compliance with study requirement, substantially
increase risk of incurring AEs or compromise the ability of the patient to give
written informed consent
- History of another primary malignancy except for :
1. Malignancy treated with curative intent and with no known active disease ≥5
years before the first dose of IP and of low potential risk for recurrence
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
3. Adequately treated carcinoma in situ without evidence of disease
- History of leptomeningeal carcinomatosis
- Study excludes patients with -brain metastases or spinal cord compression: Patients
with suspected brain metastases at screening should have an MRI (preferred) or CT
each preferably with IV contrast of the brain prior to study entry. Brain metastases
will not be recorded as RECIST Target Lesions at baseline if study allows patients
with brain metastases.
- Has untreated central nervous system (CNS) metastases and/or carcinomatous
meningitis identified either on the baseline brain imaging (RECIST)) for details on
the imaging modality) obtained during the screening period or identified prior to
signing the ICF. Patients whose brain metastases have been treated may participate
provided they show radiographic stability (defined as 2 brain images, both of which
are obtained after treatment to the brain metastases.
These imaging scans should both be obtained at least four weeks apart and show no
evidence of intracranial progression). In addition, any neurologic symptoms that
developed either as a result of the brain metastases or their treatment must have
resolved or be stable either, without the use of steroids, or are stable on a steroid
dose of ≤10mg/day of prednisone or its equivalent <<and anti-convulsants>> for at least
14 days prior to the start of treatment. Brain metastases will not be recorded as RECIST
Target Lesions at baseline.
- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms
calculated from 3 ECGs (within 15 minutes at 5 minutes apart)
- History of active primary immunodeficiency
- Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV
1/2 antibodies) or active tuberculosis infection (clinical evaluation that may
include clinical history, physical examination and radiographic findings, or
tuberculosis testing in line with local practice).
- Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and
up to 30 days after the last dose of IP.
- Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy or180 days after
the last dose of durvalumab and tremelimumab combination therapy.
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
- Prior randomisation or treatment in a previous durvalumab and/or tremelimumab
clinical study regardless of treatment arm assignment.
- Patients who have received prior anti-PD-1, anti-PD-L1 or anti-CTLA-4:
1. Must not have experienced a toxicity that led to permanent discontinuation of
prior immunotherapy.
2. All AEs while receiving prior immunotherapy must have completely resolved or
resolved to baseline prior to screening for this study.
3. Must not have experienced a ≥Grade 3 immune related AE or an immune related
neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE:
Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are
stably maintained on appropriate replacement therapy and are asymptomatic.
4. Must not have required the use of additional immunosuppression other than
corticosteroids for the management of an AE, not have experienced recurrence of
an AE if re-challenged, and not currently require maintenance doses of > 10 mg
prednisone or equivalent per day.