MelanomaPhase 1/2LIMITNCT04464759
A Study of Nivolumab and Hydroxychloroquine or Nivolumab/Ipilimumab and Hydroxychloroquine in Advanced Melanoma
A Phase 1/2 study testing Nivolumab, Hydroxychloroquine and Ipilimumab in people with Melanoma, run by Ravi Amaravadi, MD at 1 site in United States.
Trial summary
This study will evaluate the safety, tolerability and efficacy (objective response rate) of using hydroxychloroquine (HCQ) in combination with nivolumab and ipilimumab or with nivolumab alone in subjects with advanced/metastatic melanoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Nivolumab, Hydroxychloroquine and Ipilimumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Oct 2020to 12 May 2027
- Phase
- Phase 1/2
- 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
- Histological or cytological evidence of melanoma, unresectable Stage III or Stage IV, any genotype, and any programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) status
- Phase 1a: nivolumab + HCQ: any prior treatment, or treatment naïve
- Phase 2: nivolumab + HCQ:
- - - Cohort 2a: prior immunotherapy in the adjuvant or metastatic setting is required
- - - Cohort 2b: anti-PD-1 Ab-naïve, but may have received any prior other therapy
- Phase 1b nivolumab + ipilimumab + HCQ: anti-PD-1 refractory
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- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- At least one measurable site of disease by RECIST 1.1 criteria that has not been previously irradiated.
- Fresh or archived primary or metastatic tissue available for submission for correlative analyses
- Negative serum pregnancy test within 28 days prior to commencement of dosing in premenopausal women. Negative urine pregnancy test within 24 hours of starting treatment.
- Able to swallow and retain oral medication and no clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
- Adequate baseline organ function
Who cannot join
- Known serious concurrent infection or medical illness, including psychiatric disorders, which would jeopardize the ability to receive the protocol treatment with reasonable safety.
- Pregnant or breast-feeding.
- Patients with brain metastases treated with whole brain radiation that have been stable for 2 months are eligible; patients with brain metastases treated with gamma knife or surgery are allowed to participate after 2 weeks have elapsed since their procedure. Subjects are excluded if they have leptomeningeal disease or metastases causing spinal cord compression that are symptomatic or untreated or not stable for greater than or equal to 3 months (documented by imaging) or requiring corticosteroids greater than 20 mg prednisone equivalent daily.
- Must have discontinued active immunotherapy, chemotherapy, or investigational anticancer therapy at least 4 weeks prior to entering the study and oral targeted therapy at least 2 weeks prior to entering the study.
- All prior anti-cancer treatment-related toxicities (except alopecia and laboratory values listed in protocol eligibility) must be less than or equal to Grade 1 or irreversible (hypophysitis) according to the Common Terminology Criteria for Adverse Events version 5 at the time of starting treatment. Patients that are asymptomatic on low dose maintenance hormone replacement delivered at a stable dose for prior toxicities are eligible.
- Prior or concurrent cancer therapy. Active immunotherapy, chemotherapy, or investigational anticancer therapy within 4 weeks prior to entering the study or oral targeted therapy within 2 weeks prior to entering the study
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- Phase 2 nivolumab + HCQ Cohort B: No prior immunotherapy is permitted
- Patients known to be experiencing an objective partial response to immunotherapy at the time of study enrollment.
- History of malignancy other than disease under study within 3 years of study enrollment EXCEPT: history of completely resected non-melanoma skin cancer, or history of indolent second malignancies are eligible.
- Diagnosis of severe autoimmune disease requiring immunosuppressive medications. Patients with adrenal insufficiency on replacement dose steroids are eligible.
- History of interstitial lung disease or chronic pneumonitis unrelated to prior immunotherapy. Prior interstitial pneumonitis related to immunotherapy that was completely treated with no need for ongoing clinical management is allowed.
- Due to risk of disease exacerbation patients with porphyria or psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide.
- Patients receiving cytochrome P450 enzyme-inducing anticonvulsant drugs (i.e. phenytoin, carbamazepine, Phenobarbital, primidone or oxcarbazepine) within 4 weeks of the start of the study treatment
- Current use of a prohibited medication as described in section on Potential for Drug-Drug Interaction.
- History or evidence of increased cardiovascular risk
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center at University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: LIMIT Melanoma: (Lysosomal Inhibition + Melanoma ImmunoTherapy) A Phase 1/2 Open Label Trial of Nivolumab and Hydroxychloroquine or Nivolumab/Ipilimumab and Hydroxychloroquine in Patients With Advanced Melanoma
This study will evaluate the safety, tolerability and efficacy (objective response rate) of using hydroxychloroquine (HCQ) in combination with nivolumab and ipilimumab or with nivolumab alone in subjects with advanced/metastatic melanoma.
Read the detailed description
There are three parts to this Phase 1/2 study in subjects with advanced melanoma:
Phase 1a will identify the MTD and preliminary safety of combination hydroxychloroquine and nivolumab therapy.
Phase 1b will identify the MTD and preliminary safety of hydroxychloroquine administered in conjunction with nivolumab and ipilimumab therapy
Phase 2 will assess the clinical efficacy of combination hydroxychloroquine and nivolumab therapy.
- Conditions
- Melanoma
- Being tested
- Nivolumab, Hydroxychloroquine, Ipilimumab
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo®
Combination of nivolumab and hydroxychloroquine OR nivolumab, hydroxychloroquine and ipilimumab
Also called Plaquenil
Combination of nivolumab and hydroxychloroquine OR nivolumab, hydroxychloroquine and ipilimumab
IpilimumabDrug
Also called YERVOY®
Combination of nivolumab, hydroxychloroquine and ipilimumab
| Study group | Role | What they receive |
|---|---|---|
| Phase 1a: Nivolumab and Hydroxychloroquine (HCQ) | Experimental | Dose escalation:
Dose Level 1: HCQ 400 mg orally every 12 hours and nivolumab 480 mg IV every 4 weeks
Dose Level 2: HCQ 600 mg orally every 12 hours and nivolumab 480 mg IV every 4 weeks
Continue protocol treatment for up to 24 months until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-mandated study removal. Receives: Drug: Nivolumab; Drug: Hydroxychloroquine |
| Phase 2: Nivolumab and Hydroxychloroquine (HCQ) | Experimental | HCQ 400-600 mg (maximum tolerated dose from Phase 1a) orally every 12 hours and nivolumab 480 mg IV every 4 weeks
Continue protocol treatment for up to 24 months until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-mandated study removal. Receives: Drug: Nivolumab; Drug: Hydroxychloroquine |
| Phase 1b: Nivolumab + Ipilimumab +Hydroxychloroquine (HCQ) | Experimental | HCQ 400-600 mg orally every 12 hours and nivolumab 3 mg/kg IV plus ipilimumab 1 mg/kg IV every 3 weeks x4 cycles
Then 6 weeks after the last dose of ipilimumab/nivolumab begin maintenance nivolumab 480 mg IV every 4 weeks
Continue protocol treatment for up to 24 months until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-mandated study removal. Receives: Drug: Nivolumab; Drug: Hydroxychloroquine; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Maximum tolerated dose (MTD) - Number of Subjects with Dose-limiting Toxicities
To determine the MTD and preliminary safety of HCQ when administered in conjunction with one of the following treatments in patients with advanced melanoma:
- HCQ administered in combination with nivolumab; or
- HCQ administered in combination with nivolumab and ipilimumab followed by maintenance nivolumab
Measured: From first dose of protocol treatment to 16 to 32 weeks
Phase 2: Objective Response Rate (ORR)
To assess the ORR as measured by RECIST v1.1. in subjects with advanced melanoma
Measured: 12 months
Secondary outcomes (2)
Progression-free survival
The time from protocol treatment start to disease progression, death due to any cause, or last contact alive and progression-free over 24 months
Measured: From start of treatment to first progression, death due to any cause or last patient contact alive and progression-free over 24 months
1 year survival rate
Percentage of subjects alive at one year from start of treatment
Measured: From start of treatment to one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2020
- Study start21 Oct 2020
- Primary completion30 Jul 2026
- Study completion12 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ravi Amaravadi, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, Ravi Amaravadi, MD, Abramson Cancer Center at Penn Medicine
- Investigators
- Ravi Amaravadi, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04464759
- Sponsor's protocol ID
- UPCC 01620
- Other IDs
- IRB#835033
- Acronym
- LIMIT
- Status last verified
- Sep 2026
- First submitted
- 8 Jun 2020
- Last updated
- 21 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LIMIT Melanoma: (Lysosomal Inhibition + Melanoma ImmunoTherapy) A Phase 1/2 Open Label Trial of Nivolumab and Hydroxychloroquine or Nivolumab/Ipilimumab and Hydroxychloroquine in Patients With Advanced Melanoma
- ClinicalTrials.gov ID
- NCT04464759
- Acronym / sponsor ID
- LIMIT / UPCC 01620
- Conditions
- Melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Ravi Amaravadi, MDUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 21 Oct 2020 (actual)
- Primary completion
- 30 Jul 2026 (actual)
- Study completion
- 12 May 2027 (estimated)
- First posted
- 9 Jul 2020 (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.
This study will evaluate the safety, tolerability and efficacy (objective response rate) of using hydroxychloroquine (HCQ) in combination with nivolumab and ipilimumab or with nivolumab alone in subjects with advanced/metastatic melanoma.
Detailed description
There are three parts to this Phase 1/2 study in subjects with advanced melanoma:
Phase 1a will identify the MTD and preliminary safety of combination hydroxychloroquine and nivolumab therapy.
Phase 1b will identify the MTD and preliminary safety of hydroxychloroquine administered in conjunction with nivolumab and ipilimumab therapy
Phase 2 will assess the clinical efficacy of combination hydroxychloroquine and nivolumab therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase 1a: Nivolumab and Hydroxychloroquine (HCQ) | Experimental | Drug: Nivolumab, Drug: HydroxychloroquineDose escalation: Dose Level 1: HCQ 400 mg orally every 12 hours and nivolumab 480 mg IV every 4 weeks Dose Level 2: HCQ 600 mg orally every 12 hours and nivolumab 480 mg IV every 4 weeks Continue protocol treatment for up to 24 months until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-mandated study removal. |
| Phase 2: Nivolumab and Hydroxychloroquine (HCQ) | Experimental | Drug: Nivolumab, Drug: HydroxychloroquineHCQ 400-600 mg (maximum tolerated dose from Phase 1a) orally every 12 hours and nivolumab 480 mg IV every 4 weeks Continue protocol treatment for up to 24 months until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-mandated study removal. |
| Phase 1b: Nivolumab + Ipilimumab +Hydroxychloroquine (HCQ) | Experimental | Drug: Nivolumab, Drug: Hydroxychloroquine, Drug: IpilimumabHCQ 400-600 mg orally every 12 hours and nivolumab 3 mg/kg IV plus ipilimumab 1 mg/kg IV every 3 weeks x4 cycles Then 6 weeks after the last dose of ipilimumab/nivolumab begin maintenance nivolumab 480 mg IV every 4 weeks Continue protocol treatment for up to 24 months until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-mandated study removal. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histological or cytological evidence of melanoma, unresectable Stage III or Stage IV, any genotype, and any programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) status
- Phase 1a: nivolumab + HCQ: any prior treatment, or treatment naïve
- Phase 2: nivolumab + HCQ:
- - - Cohort 2a: prior immunotherapy in the adjuvant or metastatic setting is required
- - - Cohort 2b: anti-PD-1 Ab-naïve, but may have received any prior other therapy
Key exclusion criteria (16 listed)
- Known serious concurrent infection or medical illness, including psychiatric disorders, which would jeopardize the ability to receive the protocol treatment with reasonable safety.
- Pregnant or breast-feeding.
- Patients with brain metastases treated with whole brain radiation that have been stable for 2 months are eligible; patients with brain metastases treated with gamma knife or surgery are allowed to participate after 2 weeks have elapsed since their procedure. Subjects are excluded if they have leptomeningeal disease or metastases causing spinal cord compression that are symptomatic or untreated or not stable for greater than or equal to 3 months (documented by imaging) or requiring corticosteroids greater than 20 mg prednisone equivalent daily.
- Must have discontinued active immunotherapy, chemotherapy, or investigational anticancer therapy at least 4 weeks prior to entering the study and oral targeted therapy at least 2 weeks prior to entering the study.
- All prior anti-cancer treatment-related toxicities (except alopecia and laboratory values listed in protocol eligibility) must be less than or equal to Grade 1 or irreversible (hypophysitis) according to the Common Terminology Criteria for Adverse Events version 5 at the time of starting treatment. Patients that are asymptomatic on low dose maintenance hormone replacement delivered at a stable dose for prior toxicities are eligible.
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 |
|---|---|---|
| NivolumabAlso: Opdivo®Combination of nivolumab and hydroxychloroquine OR nivolumab, hydroxychloroquine and ipilimumab | Drug | Phase 1a: Nivolumab and Hydroxychloroquine (HCQ), Phase 1b: Nivolumab + Ipilimumab +Hydroxychloroquine (HCQ), Phase 2: Nivolumab and Hydroxychloroquine (HCQ) |
| HydroxychloroquineAlso: PlaquenilCombination of nivolumab and hydroxychloroquine OR nivolumab, hydroxychloroquine and ipilimumab | Drug | Phase 1a: Nivolumab and Hydroxychloroquine (HCQ), Phase 1b: Nivolumab + Ipilimumab +Hydroxychloroquine (HCQ), Phase 2: Nivolumab and Hydroxychloroquine (HCQ) |
| IpilimumabAlso: YERVOY®Combination of nivolumab, hydroxychloroquine and ipilimumab | Drug | Phase 1b: Nivolumab + Ipilimumab +Hydroxychloroquine (HCQ) |
Primary outcome
Phase 1: Maximum tolerated dose (MTD) - Number of Subjects with Dose-limiting Toxicities
Time frame: From first dose of protocol treatment to 16 to 32 weeks
To determine the MTD and preliminary safety of HCQ when administered in conjunction with one of the following treatments in patients with advanced melanoma: * HCQ administered in combination with nivolumab; or * HCQ administered in combination with nivolumab and ipilimumab followed by maintenance nivolumab
Phase 2: Objective Response Rate (ORR)
Time frame: 12 months
To assess the ORR as measured by RECIST v1.1. in subjects with advanced melanoma
2 secondary outcomes
Progression-free survival
Time frame: From start of treatment to first progression, death due to any cause or last patient contact alive and progression-free over 24 months
1 year survival rate
Time frame: From start of treatment to one year
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 21 Sep 2026.
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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. This study is not recruiting at the moment.
Ravi Amaravadi, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Nivolumab, Hydroxychloroquine and Ipilimumab in people with Melanoma, run by Ravi Amaravadi, MD at 1 site in United States.
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 12 inclusion and 16 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: under way, not looking for participants, as of the sponsor's last update on 21 Sep 2026. 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 United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Maximum tolerated dose (MTD) - Number of Subjects with Dose-limiting Toxicities (time frame: From first dose of protocol treatment to 16 to 32 weeks). 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 21 Sep 2026.