Advanced GlioblastomaPhase 214NCT05909618
Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases
A Phase 2 study testing Crizanlizumab-Tmca 10 MG/1 ML Intravenous Solution [ADAKVEO] and Nivolumab 10 MG/1 ML Intravenous Solution [OPDIVO] in people with Advanced Glioblastoma and Metastatic Melanoma in the Central Nervous System, run by Sheba Medical Center at 1 site in Israel.
Trial summary
A single-center, open-label, non-randomized phase I/II study to evaluate the efficacy, safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma (GB) who exhausted standard of care (SOC) therapy, patients with metastatic brain melanoma (MBM) and patients… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Glioblastoma, Metastatic Melanoma in the Central Nervous System, MGMT-Unmethylated Glioblastoma
- What is being tested?
- Crizanlizumab-Tmca 10 MG/1 ML Intravenous Solution [ADAKVEO] and Nivolumab 10 MG/1 ML Intravenous Solution [OPDIVO]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteIsrael
- Study dates
- 11 Jul 2023to 30 Jul 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Systemic steroid therapy for symptomatic brain disease. Note: a dose equivalent to 10 mg prednisone will be allowed
- Have leptomeningeal spread.
- Previous life-threatening toxicity to anti-PD-1 antibody monotherapy.
- Auto-immune disease in the last 2 years requiring systemic immune-suppressive therapy.
- Previous exposure to Crizanlizumab or any other P-selectin inhibitor.
- Previous or current brain hemorrhage.
Show all 57Show fewer
- The patient had, or is expected to undergo, allogeneic hematopoietic stem cell transplantation (HSCT).
- The patient had a contraindication for undergoing brain MRI.
- Any other severe concurrent disease which, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
- Pregnant or lactating
- Treatment with other investigational drugs within <21 days of start of day 1 of the study treatment.
- Any contraindication for treatment with nivolumab according to the product's labels.
- Cohort 2 (Recurrent or Progressive GB) Inclusion Criteria
- Age ≥ 18 years.
- Estimated life expectancy at least 3 months
- Have with recurrent or persistent GB
- Received first line therapy with brain irradiation and maintenance temozolamide.
- Measurable disease per RANO criteria on brain MRI.
- Have Eastern Cooperative Oncology Group (ECOG) performance status <2.
- Adequate organ function defined by blood tests for blood count and chemistry.
- Women of childbearing potential practicing an acceptable method of birth control.
- Understand study procedures and willingness to comply for the entire duration of the study and to give written informed consent.
- Systemic steroid therapy for symptomatic brain disease. Note: a dose equivalent to 20 mg prednisone will be allowed
- Have leptomeningeal spread.
- Previous life-threatening toxicity to anti-PD-1 antibody monotherapy.
- Auto-immune disease in the last 2 years requiring systemic immune-suppressive therapy.
- Previous exposure to Crizanlizumab or any other P-selectin inhibitor.
- Previous or current brain hemorrhage.
- The patient had, or is expected to undergo, allogeneic HSCT.
- The patient had a contraindication for undergoing brain MRI.
- Any other severe concurrent disease which, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
- Pregnant or lactating
- Treatment with other investigational drugs within <21 days of start of day 1 of the study treatment.
- Any contraindication for treatment with nivolumab according to the product's labels.
- Cohort 3 (Newly Diagnosed Unmethylated GB) Inclusion Criteria
- Age ≥ 18 years.
- Estimated life expectancy at least 3 months.
- Histologically confirmed newly diagnosed GB.
- Tumor test result shows MGMT unmethylated type.
- Received definitive brain irradiation.
- Patients may be treated with novo TTF (optune) per local standard.
- Have Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
- Adequate organ function defined by blood tests for blood count and chemistry.
- Women of childbearing potential practicing an acceptable method of birth control.
- Understand study procedures and willingness to comply for the entire duration of the study and to give written informed consent.
- Systemic steroid therapy for symptomatic brain disease. Note: a dose equivalent to 20 mg prednisone will be allowed
- Have leptomeningeal spread.
- Previous life-threatening toxicity to anti-PD-1 antibody monotherapy.
- Auto-immune disease in the last 2 years requiring systemic immune-suppressive therapy.
- Previous exposure to Crizanlizumab or any other P-selectin inhibitor.
- Previous or current brain hemorrhage.
- The patient had, or is expected to undergo, allogeneic HSCT.
- The patient had a contraindication for undergoing brain MRI.
- Any other severe concurrent disease which, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
- Be pregnant or lactating
- Treatment with other investigational drugs within <21 days of start of day 1 of the study treatment.
- Any contraindication for treatment with nivolumab according to the product's labels
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site, 1 recruiting
- Recruiting
Sheba medical center
Ramat Gan, Israel
Ronnie Shapira, MD, Ronnie.Shapira@sheba.health.gov
Meital Bar, 972-3-5305201, meital.bar@sheba.health.gov.il
About this study
Official title: An Open Label Phase 2 Study of Intravenously Administered Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases
A single-center, open-label, non-randomized phase I/II study to evaluate the efficacy, safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma (GB) who exhausted standard of care (SOC) therapy, patients with metastatic brain melanoma (MBM) and patients with newly diagnosed unmethylated GB.
Subjects will be screened for up to 28 days prior to treatment initiation. Eligible subjects will be allocated to one of 3 cohorts:
Read more
Cohort 1: Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy.
Cohort 2: Patients with recurrent or progressing GB following primary radiation therapy and temozolomide. Patients may have failed up to 2 prior systemic treatment lines (including temozolomide as adjuvant therapy) and are candidates for further treatment.
Cohort 3: Patients with newly diagnosed GB who were evaluated for methylguanine-DNA methyltransferase(MGMT) methylation status and have un-methylated MGMT promotor-therefore, they are not candidates for maintenance temozolomide therapy.
Read the detailed description
A single-center, open-label, non-randomized phase I/II study to evaluate the efficacy, safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma (GB) who exhausted standard of care (SOC) therapy, patients with metastatic brain melanoma (MBM) and patients with newly diagnosed unmethylated GB.
Subjects will be screened for up to 28 days prior to treatment initiation. Eligible subjects will be allocated to one of 3 cohorts:
Cohort 1: Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy.
Cohort 2: Patients with recurrent or progressing GB following primary radiation therapy and temozolomide. Patients may have failed up to 2 prior systemic treatment lines (including temozolomide as adjuvant therapy) and are candidates for further treatment.
Cohort 3: Patients with newly diagnosed GB who were evaluated for MGMT methylation status and have un-methylated MGMT promotor-therefore, they are not candidates for maintenance temozolomide therapy.
The first 3 subjects enrolled to Cohort 1 and Cohort 2 will receive crizanlizumab 5 mg/kg at Cycle 1 Day 1 (C1D1) and Cycle 1 Day 15 (C1D15) followed by crizanlizumab 5 mg/kg every 4 weeks until disease progression evaluated by RECIST 1.1 and RANO criteria or intolerable toxicity. The subsequent 8 patients will receive crizanlizumab 5 miligram/kilogram (mg/kg) at C1D1 and C1D15 followed by 5 mg/kg every 4 weeks plus nivolumab 3mg/kg every 2 weeks until disease progression. The subjects will continue the treatment until disease progression or until completion of 27 cycles (2 years). Subjects who complete 2 years of therapy will maintain follow-up.
Subjects in Cohort 3 will receive crizanlizumab starting from 4 weeks after completing radiation therapy. The first 2 subjects will receive crizanlizumab 2.5 mg/kg at C1D1 and C1D15 followed by crizanlizumab 5 mg/kg every 4 weeks. The subsequent 6 subjects will receive crizanlizumab 5 mg/kg at C1D1 and C1D15 followed by crizanlizumab every 4 weeks. Treatment will continue for up to 12 months or until disease progression or unacceptable toxicity.
Safety and tolerability will be assessed by CTCAE v 6.0 every week for the first 4 weeks followed by assessments every 2 weeks until Week 12, and then every 4 weeks.
Tumor response will be evaluated by brain Magnetic resonance imaging (MRI) every 8 weeks using RANO criteria. Patients with metastatic melanoma will also be evaluated with chest-abdomen and pelvis Computed tomography (CT) every 8 weeks for the evaluation of visceral disease using RECIST 1.1.
Patients with MBM (Cohort 1) whose primary tumor/non-brain tumor progresses on RECIST 1.1 but whose brain tumor/metastases show benefit (stable disease or better), may continue in the study at the investigator's discretion.
Quality of life will be assessed by the Quality of Life Questionnaire (EORTC QLQ-30) and Brain Neoplasm(QLQ BN-20) and by cognitive function tests.
Archived tissue samples (and optional fresh biopsy), CSF and blood samples will be drawn to assess pharmacokinetics and pharmacodynamics of the combined therapy and for collateral research aiming to define biomarkers for response.
- Conditions
- Advanced Glioblastoma, Metastatic Melanoma in the Central Nervous System, MGMT-Unmethylated Glioblastoma
- Being tested
- Crizanlizumab-Tmca 10 MG/1 ML Intravenous Solution [ADAKVEO], Nivolumab 10 MG/1 ML Intravenous Solution [OPDIVO]
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Crizanlizumab-Tmca 10 MG/1 ML Intravenous Solution [ADAKVEO]Drug
Also called crizanlizumab
5 mg/kg solution for injection
Nivolumab 10 MG/1 ML Intravenous Solution [OPDIVO]Drug
Also called nivolumab
3 mg/mL solution for injection
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 metastatic melanoma with brain metastases who failed immunotherapy | Experimental | The first 3 subjects enrolled to Cohort 1 and Cohort 2 will receive crizanlizumab 5 mg/kg at Cycle 1 Day 1 (C1D1) and C1D15 followed by crizanlizumab 5 mg/kg every 4 weeks until disease progression The subsequent 8 patients will receive crizanlizumab 5 mg/kg at C1D1 and C1D15 followed by 5 mg/kg every 4 weeks plus nivolumab 3mg/kg every 2 weeks until disease progression |
| Cohort 2 - Patients with recurrent or progressing GB following radiation and temozolamide. | Experimental | The first 3 subjects enrolled to Cohort 1 and Cohort 2 will receive crizanlizumab 5 mg/kg at Cycle 1 Day 1 (C1D1) and C1D15 followed by crizanlizumab 5 mg/kg every 4 weeks until disease progression The subsequent 8 patients will receive crizanlizumab 5 mg/kg at C1D1 and C1D15 followed by 5 mg/kg every 4 weeks plus nivolumab 3mg/kg every 2 weeks until disease progression Receives: Drug: Crizanlizumab-Tmca 10 MG/1 ML Intravenous Solution [ADAKVEO]; Drug: Nivolumab 10 MG/1 ML Intravenous Solution [OPDIVO] |
| Cohort 3: Patients with newly diagnosed GB | Experimental | crizanlizumab starting from 4 weeks after completing radiation therapy. The first 2 subjects will receive crizanlizumab 2.5 mg/kg at C1D1 and C1D15 followed by crizanlizumab 5 mg/kg every 4 weeks. The subsequent 6 subjects will receive crizanlizumab 5 mg/kg at C1D1 and C1D15 followed by crizanlizumab every 4 weeks. Treatment will continue for up to 12 months or until disease progression or unacceptable toxicity. Receives: Drug: Crizanlizumab-Tmca 10 MG/1 ML Intravenous Solution [ADAKVEO] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-related adverse, serious adverse events, immune-related AEs following treatment with crizanlizumab alone or in combination with nivolumab
Safety and tolerability assessed by CTCAE v 6.0
Measured: 48 months
The proportion of treatment discontinuation events related to the treatment combination
Safety and tolerability assessed by CTCAE v 6.0
Measured: 48 months
Secondary outcomes (6)
Response Rate (RR) to crizanlizumab monotherapy and in combination with nivolumab
evaluated by RECIST 1.1 and by RANO and RANO-BM criteria.
Measured: 48 months
Progression-free survival (PFS) of patients with GB or MBM following treatment crizanlizumab monotherapy and in combination with nivolumab
by brain MRI and CT of chest/abdomen and pelvis using RECIST 1.1 and RANO/RANO-BM criteria
Measured: evaluated every 8 weeks for 48 months
Overall survival (OS) in patients with GB or MBM following treatment crizanlizumab monotherapy and in combination with nivolumab.
Overall survival (OS) of the study population
Measured: 48 months
Impact of the treatment protocol on health-related quality of life
using EORTC questionnaires ,All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
Measured: evaluated every 6 weeks for 48 months
Incidence of treatment-related adverse, serious adverse events, immune-related AEs of crizanlizumab maintenance therapy following whole-brain irradiation in patients with unmethylated GB
evaluated by adverse events monitoring using CTCAE Version 6.0 and by documenting study treatment discontinuation and delays.
Measured: 48 months
Disease control rate (DCR)
valuated by rate of progression in patients with un-methylated GB treated with crizanlizumab maintenance therapy following whole-brain irradiation.
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2023
- Study start11 Jul 2023
- Primary completion30 Jul 2028 (estimated)
- Study completion30 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced GlioblastomaStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Collaborators
- Prof. Ronit Satchi-Fainaro, Director, Cancer Biology Research Center, Tel Aviv University, Tel Aviv, Israel.
- Responsible party
- Principal investigator, Dr. Ronnie Shapira, Sheba Medical Center
- Investigators
- Ronnie Shapira Frommer, Dr, Principal investigator, Ronnie Shapira, MD Study Principal Investigator Ronnie.Shapira@sheba.health.gov.il
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05909618
- Sponsor's protocol ID
- Sheba-9411-22-RS-crizanlizumab
- Acronym
- 14
- Status last verified
- Jul 2025
- First submitted
- 1 May 2023
- Last updated
- 22 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Phase 2 Study of Intravenously Administered Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases
- ClinicalTrials.gov ID
- NCT05909618
- Acronym / sponsor ID
- 14 / Sheba-9411-22-RS-crizanlizumab
- Conditions
- Advanced Glioblastoma, Metastatic Melanoma in the Central Nervous System, MGMT-Unmethylated Glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- Sheba Medical CenterOther government
- Collaborators
- Prof. Ronit Satchi-Fainaro, Director, Cancer Biology Research Center, Tel Aviv University, Tel Aviv, Israel.
- Study start
- 11 Jul 2023 (actual)
- Primary completion
- 30 Jul 2028 (estimated)
- Study completion
- 30 Jul 2030 (estimated)
- First posted
- 18 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A single-center, open-label, non-randomized phase I/II study to evaluate the efficacy, safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma (GB) who exhausted standard of care (SOC) therapy, patients with metastatic brain melanoma (MBM) and patients with newly diagnosed unmethylated GB.
Subjects will be screened for up to 28 days prior to treatment initiation. Eligible subjects will be allocated to one of 3 cohorts:
Cohort 1: Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy.
Cohort 2: Patients with recurrent or progressing GB following primary radiation therapy and temozolomide. Patients may have failed up to 2 prior systemic treatment lines (including temozolomide as adjuvant therapy) and are candidates for further treatment.
Cohort 3: Patients with newly diagnosed GB who were evaluated for methylguanine-DNA methyltransferase(MGMT) methylation status and have un-methylated MGMT promotor-therefore, they are not candidates for maintenance temozolomide therapy.
Detailed description
A single-center, open-label, non-randomized phase I/II study to evaluate the efficacy, safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma (GB) who exhausted standard of care (SOC) therapy, patients with metastatic brain melanoma (MBM) and patients with newly diagnosed unmethylated GB.
Subjects will be screened for up to 28 days prior to treatment initiation. Eligible subjects will be allocated to one of 3 cohorts:
Cohort 1: Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy.
Cohort 2: Patients with recurrent or progressing GB following primary radiation therapy and temozolomide. Patients may have failed up to 2 prior systemic treatment lines (including temozolomide as adjuvant therapy) and are candidates for further treatment.
Cohort 3: Patients with newly diagnosed GB who were evaluated for MGMT methylation status and have un-methylated MGMT promotor-therefore, they are not candidates for maintenance temozolomide therapy.
The first 3 subjects enrolled to Cohort 1 and Cohort 2 will receive crizanlizumab 5 mg/kg at Cycle 1 Day 1 (C1D1) and Cycle 1 Day 15 (C1D15) followed by crizanlizumab 5 mg/kg every 4 weeks until disease progression evaluated by RECIST 1.1 and RANO criteria or intolerable toxicity. The subsequent 8 patients will receive crizanlizumab 5 miligram/kilogram (mg/kg) at C1D1 and C1D15 followed by 5 mg/kg every 4 weeks plus nivolumab 3mg/kg every 2 weeks until disease progression. The subjects will continue the treatment until disease progression or until completion of 27 cycles (2 years). Subjects who complete 2 years of therapy will maintain follow-up.
Subjects in Cohort 3 will receive crizanlizumab starting from 4 weeks after completing radiation therapy. The first 2 subjects will receive crizanlizumab 2.5 mg/kg at C1D1 and C1D15 followed by crizanlizumab 5 mg/kg every 4 weeks. The subsequent 6 subjects will receive crizanlizumab 5 mg/kg at C1D1 and C1D15 followed by crizanlizumab every 4 weeks. Treatment will continue for up to 12 months or until disease progression or unacceptable toxicity.
Safety and tolerability will be assessed by CTCAE v 6.0 every week for the first 4 weeks followed by assessments every 2 weeks until Week 12, and then every 4 weeks.
Tumor response will be evaluated by brain Magnetic resonance imaging (MRI) every 8 weeks using RANO criteria. Patients with metastatic melanoma will also be evaluated with chest-abdomen and pelvis Computed tomography (CT) every 8 weeks for the evaluation of visceral disease using RECIST 1.1.
Patients with MBM (Cohort 1) whose primary tumor/non-brain tumor progresses on RECIST 1.1 but whose brain tumor/metastases show benefit (stable disease or better), may continue in the study at the investigator's discretion.
Quality of life will be assessed by the Quality of Life Questionnaire (EORTC QLQ-30) and Brain Neoplasm(QLQ BN-20) and by cognitive function tests.
Archived tissue samples (and optional fresh biopsy), CSF and blood samples will be drawn to assess pharmacokinetics and pharmacodynamics of the combined therapy and for collateral research aiming to define biomarkers for response.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 metastatic melanoma with brain metastases who failed immunotherapy | Experimental | –The first 3 subjects enrolled to Cohort 1 and Cohort 2 will receive crizanlizumab 5 mg/kg at Cycle 1 Day 1 (C1D1) and C1D15 followed by crizanlizumab 5 mg/kg every 4 weeks until disease progression The subsequent 8 patients will receive crizanlizumab 5 mg/kg at C1D1 and C1D15 followed by 5 mg/kg every 4 weeks plus nivolumab 3mg/kg every 2 weeks until disease progression |
| Cohort 2 - Patients with recurrent or progressing GB following radiation and temozolamide. | Experimental | Drug: Crizanlizumab-Tmca 10 MG/1 ML Intravenous Solution [ADAKVEO], Drug: Nivolumab 10 MG/1 ML Intravenous Solution [OPDIVO]The first 3 subjects enrolled to Cohort 1 and Cohort 2 will receive crizanlizumab 5 mg/kg at Cycle 1 Day 1 (C1D1) and C1D15 followed by crizanlizumab 5 mg/kg every 4 weeks until disease progression The subsequent 8 patients will receive crizanlizumab 5 mg/kg at C1D1 and C1D15 followed by 5 mg/kg every 4 weeks plus nivolumab 3mg/kg every 2 weeks until disease progression |
| Cohort 3: Patients with newly diagnosed GB | Experimental | Drug: Crizanlizumab-Tmca 10 MG/1 ML Intravenous Solution [ADAKVEO]crizanlizumab starting from 4 weeks after completing radiation therapy. The first 2 subjects will receive crizanlizumab 2.5 mg/kg at C1D1 and C1D15 followed by crizanlizumab 5 mg/kg every 4 weeks. The subsequent 6 subjects will receive crizanlizumab 5 mg/kg at C1D1 and C1D15 followed by crizanlizumab every 4 weeks. Treatment will continue for up to 12 months or until disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (57 listed)
- Systemic steroid therapy for symptomatic brain disease. Note: a dose equivalent to 10 mg prednisone will be allowed
- Have leptomeningeal spread.
- Previous life-threatening toxicity to anti-PD-1 antibody monotherapy.
- Auto-immune disease in the last 2 years requiring systemic immune-suppressive therapy.
- Previous exposure to Crizanlizumab or any other P-selectin inhibitor.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Crizanlizumab-Tmca 10 MG/1 ML Intravenous Solution [ADAKVEO]Also: crizanlizumab5 mg/kg solution for injection | Drug | Cohort 2 - Patients with recurrent or progressing GB following radiation and temozolamide., Cohort 3: Patients with newly diagnosed GB |
| Nivolumab 10 MG/1 ML Intravenous Solution [OPDIVO]Also: nivolumab3 mg/mL solution for injection | Drug | Cohort 2 - Patients with recurrent or progressing GB following radiation and temozolamide. |
Primary outcome
Incidence of treatment-related adverse, serious adverse events, immune-related AEs following treatment with crizanlizumab alone or in combination with nivolumab
Time frame: 48 months
Safety and tolerability assessed by CTCAE v 6.0
The proportion of treatment discontinuation events related to the treatment combination
Time frame: 48 months
Safety and tolerability assessed by CTCAE v 6.0
6 secondary outcomes
Response Rate (RR) to crizanlizumab monotherapy and in combination with nivolumab
Time frame: 48 months
Progression-free survival (PFS) of patients with GB or MBM following treatment crizanlizumab monotherapy and in combination with nivolumab
Time frame: evaluated every 8 weeks for 48 months
Overall survival (OS) in patients with GB or MBM following treatment crizanlizumab monotherapy and in combination with nivolumab.
Time frame: 48 months
Impact of the treatment protocol on health-related quality of life
Time frame: evaluated every 6 weeks for 48 months
Incidence of treatment-related adverse, serious adverse events, immune-related AEs of crizanlizumab maintenance therapy following whole-brain irradiation in patients with unmethylated GB
Time frame: 48 months
Disease control rate (DCR)
Time frame: 48 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ronnie Shapira Frommer, Dr principal investigator
Ronnie Shapira, MD Study Principal Investigator Ronnie.Shapira@sheba.health.gov.il
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Crizanlizumab-Tmca 10 MG/1 ML Intravenous Solution [ADAKVEO] and Nivolumab 10 MG/1 ML Intravenous Solution [OPDIVO] in people with Advanced Glioblastoma and Metastatic Melanoma in the Central Nervous System, run by Sheba Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 57 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ronnie Shapira Frommer, Dr (972-3-5302243, ronnie.shapira@sheba.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-related adverse, serious adverse events, immune-related AEs following treatment with crizanlizumab alone or in combination with nivolumab (time frame: 48 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2025.