Trial Outcomes & Findings for Intravenous Chemotherapy or Oral Chemotherapy in Treating Patients With Previously Untreated Stage III-IV HIV-Associated Non-Hodgkin Lymphoma (NCT NCT01775475)
NCT ID: NCT01775475
Last Updated: 2022-10-10
Results Overview
Proportion of participants who survived 2 years
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
7 participants
Primary outcome timeframe
Up to 24 months
Results posted on
2022-10-10
Participant Flow
Participant milestones
| Measure |
Arm I (CHOP)
Patients receive CHOP chemotherapy comprising cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Given IV
doxorubicin hydrochloride: Given IV
vincristine sulfate: Given IV
prednisone: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Oral Chemotherapy)
Patients receive lomustine PO QD on day 1 (courses 1 and 3 only), etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
lomustine: Given PO
etoposide: Given PO
cyclophosphamide: Given PO
procarbazine hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Overall Study
STARTED
|
4
|
3
|
|
Overall Study
COMPLETED
|
1
|
0
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
Reasons for withdrawal
| Measure |
Arm I (CHOP)
Patients receive CHOP chemotherapy comprising cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Given IV
doxorubicin hydrochloride: Given IV
vincristine sulfate: Given IV
prednisone: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Oral Chemotherapy)
Patients receive lomustine PO QD on day 1 (courses 1 and 3 only), etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
lomustine: Given PO
etoposide: Given PO
cyclophosphamide: Given PO
procarbazine hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Overall Study
Death
|
3
|
3
|
Baseline Characteristics
Intravenous Chemotherapy or Oral Chemotherapy in Treating Patients With Previously Untreated Stage III-IV HIV-Associated Non-Hodgkin Lymphoma
Baseline characteristics by cohort
| Measure |
Arm I (CHOP)
n=4 Participants
Patients receive CHOP chemotherapy comprising cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Given IV
doxorubicin hydrochloride: Given IV
vincristine sulfate: Given IV
prednisone: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Oral Chemotherapy)
n=3 Participants
Patients receive lomustine PO QD on day 1 (courses 1 and 3 only), etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
lomustine: Given PO
etoposide: Given PO
cyclophosphamide: Given PO
procarbazine hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
Total
n=7 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52.5 years
n=5 Participants
|
46.0 years
n=7 Participants
|
47.0 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Zimbabwe
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Kenya
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Region of Enrollment
Malawi
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 24 monthsPopulation: Study participants whose survival status was known at two years.
Proportion of participants who survived 2 years
Outcome measures
| Measure |
Arm I (CHOP)
n=3 Participants
Patients receive CHOP chemotherapy comprising cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Given IV
doxorubicin hydrochloride: Given IV
vincristine sulfate: Given IV
prednisone: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Oral Chemotherapy)
n=3 Participants
Patients receive lomustine PO QD on day 1 (courses 1 and 3 only), etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
lomustine: Given PO
etoposide: Given PO
cyclophosphamide: Given PO
procarbazine hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Overall Survival
|
0 Proportion of participants
Interval 0.0 to 0.0
|
0 Proportion of participants
Interval 0.0 to 0.0
|
PRIMARY outcome
Timeframe: Up to 24 monthsOverall response is complete or partial response as defined by response definitions of the 2014 International Conference on Malignant Lymphoma Imaging Working Group (i.e. Lugano classification). Complete response is the disappearance of all lesions with no new lesions detected. Partial response is \>=50% decrease in the sum of the perpendicular diameters of up to 6 target measurable nodes and extranodal sites and no new sites of disease.
Outcome measures
| Measure |
Arm I (CHOP)
n=4 Participants
Patients receive CHOP chemotherapy comprising cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Given IV
doxorubicin hydrochloride: Given IV
vincristine sulfate: Given IV
prednisone: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Oral Chemotherapy)
n=3 Participants
Patients receive lomustine PO QD on day 1 (courses 1 and 3 only), etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
lomustine: Given PO
etoposide: Given PO
cyclophosphamide: Given PO
procarbazine hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Overall Response Rate
|
3 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Up to 24 monthsPopulation: Participants whose disease and survival status were known at 2 years
Proportion of participants who survived without disease progression at 2 years
Outcome measures
| Measure |
Arm I (CHOP)
n=3 Participants
Patients receive CHOP chemotherapy comprising cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Given IV
doxorubicin hydrochloride: Given IV
vincristine sulfate: Given IV
prednisone: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Oral Chemotherapy)
n=3 Participants
Patients receive lomustine PO QD on day 1 (courses 1 and 3 only), etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
lomustine: Given PO
etoposide: Given PO
cyclophosphamide: Given PO
procarbazine hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Progression-free Survival
|
0 proportion
Interval 0.0 to 0.0
|
0 proportion
Interval 0.0 to 0.0
|
PRIMARY outcome
Timeframe: Up to 24 monthsNumber of participants who experienced an adverse event
Outcome measures
| Measure |
Arm I (CHOP)
n=4 Participants
Patients receive CHOP chemotherapy comprising cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Given IV
doxorubicin hydrochloride: Given IV
vincristine sulfate: Given IV
prednisone: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Oral Chemotherapy)
n=3 Participants
Patients receive lomustine PO QD on day 1 (courses 1 and 3 only), etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
lomustine: Given PO
etoposide: Given PO
cyclophosphamide: Given PO
procarbazine hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Participants Who Experienced an Adverse Event
|
4 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: Up to 18 weeksNumber of patients who complete chemotherapy treatment.
Outcome measures
| Measure |
Arm I (CHOP)
n=4 Participants
Patients receive CHOP chemotherapy comprising cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Given IV
doxorubicin hydrochloride: Given IV
vincristine sulfate: Given IV
prednisone: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Oral Chemotherapy)
n=3 Participants
Patients receive lomustine PO QD on day 1 (courses 1 and 3 only), etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
lomustine: Given PO
etoposide: Given PO
cyclophosphamide: Given PO
procarbazine hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Number of Patients Who Complete Treatment
|
3 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Up to 24 monthsNumber of patients who did not miss any of their doses of antiretroviral therapy
Outcome measures
| Measure |
Arm I (CHOP)
n=4 Participants
Patients receive CHOP chemotherapy comprising cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Given IV
doxorubicin hydrochloride: Given IV
vincristine sulfate: Given IV
prednisone: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Oral Chemotherapy)
n=3 Participants
Patients receive lomustine PO QD on day 1 (courses 1 and 3 only), etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
lomustine: Given PO
etoposide: Given PO
cyclophosphamide: Given PO
procarbazine hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Proportion of Patients Who Are Adherent to Antiretroviral Therapy
|
3 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: Up to 18 weeksPatients who did not miss any doses of chemotherapy
Outcome measures
| Measure |
Arm I (CHOP)
n=4 Participants
Patients receive CHOP chemotherapy comprising cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Given IV
doxorubicin hydrochloride: Given IV
vincristine sulfate: Given IV
prednisone: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Oral Chemotherapy)
n=3 Participants
Patients receive lomustine PO QD on day 1 (courses 1 and 3 only), etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
lomustine: Given PO
etoposide: Given PO
cyclophosphamide: Given PO
procarbazine hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Proportion of Patients Who Are Adherent to Chemotherapy
|
4 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: From baseline to 18 weeksPopulation: Participants who had absolute CD4 count measurements at baseline and visit 6
Change in absolute CD4 count from baseline to post-treatment (visit 6)
Outcome measures
| Measure |
Arm I (CHOP)
n=3 Participants
Patients receive CHOP chemotherapy comprising cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Given IV
doxorubicin hydrochloride: Given IV
vincristine sulfate: Given IV
prednisone: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Oral Chemotherapy)
n=3 Participants
Patients receive lomustine PO QD on day 1 (courses 1 and 3 only), etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
lomustine: Given PO
etoposide: Given PO
cyclophosphamide: Given PO
procarbazine hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Change in Absolute CD4 Count From Baseline to Post-treatment
|
-41.3 cells per mm^3
Standard Deviation 136.5
|
203.3 cells per mm^3
Standard Deviation 153.1
|
Adverse Events
Arm I (CHOP)
Serious events: 4 serious events
Other events: 4 other events
Deaths: 3 deaths
Arm II (Oral Chemotherapy)
Serious events: 3 serious events
Other events: 3 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Arm I (CHOP)
n=4 participants at risk
Patients receive CHOP chemotherapy comprising cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Given IV
doxorubicin hydrochloride: Given IV
vincristine sulfate: Given IV
prednisone: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Oral Chemotherapy)
n=3 participants at risk
Patients receive lomustine PO QD on day 1 (courses 1 and 3 only), etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
lomustine: Given PO
etoposide: Given PO
cyclophosphamide: Given PO
procarbazine hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms, other
|
50.0%
2/4 • 2 years
|
66.7%
2/3 • 2 years
|
|
General disorders
Fatigue
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Infections and infestations
Encephalitis infection
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Nervous system disorders
Headache
|
50.0%
2/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
General disorders
Fever
|
0.00%
0/4 • 2 years
|
33.3%
1/3 • 2 years
|
|
General disorders
Death cause unknown
|
0.00%
0/4 • 2 years
|
33.3%
1/3 • 2 years
|
Other adverse events
| Measure |
Arm I (CHOP)
n=4 participants at risk
Patients receive CHOP chemotherapy comprising cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Given IV
doxorubicin hydrochloride: Given IV
vincristine sulfate: Given IV
prednisone: Given PO
laboratory biomarker analysis: Correlative studies
|
Arm II (Oral Chemotherapy)
n=3 participants at risk
Patients receive lomustine PO QD on day 1 (courses 1 and 3 only), etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
lomustine: Given PO
etoposide: Given PO
cyclophosphamide: Given PO
procarbazine hydrochloride: Given PO
laboratory biomarker analysis: Correlative studies
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
25.0%
1/4 • 2 years
|
33.3%
1/3 • 2 years
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders, other
|
25.0%
1/4 • 2 years
|
33.3%
1/3 • 2 years
|
|
Eye disorders
Tinnitus
|
0.00%
0/4 • 2 years
|
33.3%
1/3 • 2 years
|
|
Eye disorders
Blurred vision
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/4 • 2 years
|
33.3%
1/3 • 2 years
|
|
Gastrointestinal disorders
Dysphagia
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
1/4 • 2 years
|
33.3%
1/3 • 2 years
|
|
General disorders
Fatigue
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
General disorders
Fever
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Infections and infestations
Otitis externa
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Investigations
Alkaline phosphatase
|
25.0%
1/4 • 2 years
|
66.7%
2/3 • 2 years
|
|
Investigations
GGT increased
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/4 • 2 years
|
33.3%
1/3 • 2 years
|
|
Investigations
Neutrophil count decreased
|
50.0%
2/4 • 2 years
|
33.3%
1/3 • 2 years
|
|
Investigations
White blood cell decreased
|
25.0%
1/4 • 2 years
|
33.3%
1/3 • 2 years
|
|
Metabolism and nutrition disorders
Anorexia
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Metabolism and nutrition disorders
Hypernatremia
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
25.0%
1/4 • 2 years
|
66.7%
2/3 • 2 years
|
|
Nervous system disorders
Facial nerve disorder
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Skin and subcutaneous tissue disorders
Nail coloration
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Vascular disorders
Hypertension
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
|
Vascular disorders
Hypotension
|
25.0%
1/4 • 2 years
|
0.00%
0/3 • 2 years
|
Additional Information
Study Statistician
AIDS Malignancy Consortium Statistical and Data Analysis Center
Phone: (212) 659-9558
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place