Hematologic MalignanciesPhase 1NCT02985554

Phase I Study to Assess the Tolerability and Efficacy of Nivolumab in Patients With Hematologic Malignancies

A Phase 1 study testing Nivolumab in people with Hematologic Malignancies, run by University of Chicago at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Hematologic Malignancies
What is being tested?: Nivolumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3 participants
Where: 1 siteUnited States
Study dates: 20 Mar 2017to 22 Jun 2020
Phase: Phase 1
Are there results?: None posted in the registry

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

Patients with hematologic malignancies status post allogeneic SCT without evidence of disease relapse, active GVHD or history of more than Stage I skin acute GVHD; and off immunosuppression for at least 4 weeks. At least 60 days after allo-SCT.
Patients with high risk myeloid or lymphoid malignancies at stem cell transplant following ASBMT criteria (http://www.asbmt.org/displaycommon.cfm?an=1\&subarticlenbr=35, under disease classification), including but not limited to conditions listed. Refractory acute myelogenous or lymphoid leukemia Relapsed acute myelogenous or lymphoid leukemia Myelodysplastic syndromes with 5% or more blasts Chronic myelogenous leukemia in chronic phase 3 or more, blast phase presently, or second accelerated phase, Recurrent or refractory malignant lymphoma or Hodgkin's disease with less than a partial response at transplant High risk chronic lymphocytic leukemia defined as no response or stable disease to the most recent treatment regimen.
Age ≥18 years. Because no dosing or adverse event data are currently available on the use of nivolumab in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
ECOG/Karnofsky performance status of 0 or 1 (Karnofsky ≥70%, see Appendix A).
Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to treatment.
leukocytes ≥2000/mcL

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absolute neutrophil count ≥1,000/mcL(In the absence of growth factor support)
platelets ≥50,000/mcL or recovery to the baseline count(in the absence of transfusion)Hgb >9.0g/dL
total bilirubin ≤1.5× institutional upper limit of normal (ULN) (except patients with Gilbert Syndrome, who can have total bilirubin <3.0 mg/dL)
AST(SGOT)/ALT(SGPT) ≤3 × ULN 17
Serum creatinine ≤1.5× ULN OR
creatinine clearance (CrCl) ≥40 mL/min (if using the Cockcroft-Gault formula below): Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP should use an adequate method to avoid pregnancy for 23 weeks) after the last dose of investigational drug Nivolumab. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab. Women must not be breastfeeding. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception. Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately. 18
Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

History of allergy to study drug components.
Patients who have disease relapse, active GVHD or history of more than Stage 1 skin acute GVHD, history of cGVHD.
Patients with active infection, un-resolving more than grade 2 transplant-related toxicities.
Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier.
Patients who are receiving any other investigational agents.
Patients with known CNS involvement may be excluded because of poor prognosis and concerns regarding progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, if CNS disease is cleared before the treatment with Nivolumab, patients could be allowed if no permanent CNS damage.

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History of severe hypersensitivity reaction to any monoclonal antibody.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study because Nivolumab is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Nivolumab, breastfeeding should be discontinued if the mother is treated with Nivolumab.
Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) might be enrolled if the viral load by PCR is undetectable with/without active treatment and absolute lymphocyte count >= 350/ul. Patients with a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection might be enrolled if the viral load by PCR is undetectable with/without active treatment.
Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as SLE, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjögren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event).
Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses <10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intraarticular, intranasal, and inhalational corticosteroids (with minimal systemic absorption).
Physiologic replacement doses of systemic corticosteroids are permitted, even if <10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study.eligible. Patients with rheumatoid arthritis and other arthropathies, Sjögren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event).
Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses <10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intraarticular, intranasal, and inhalational corticosteroids (with minimal systemic absorption).
Physiologic replacement doses of systemic corticosteroids are permitted, even if <10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Chicago
Chicago, Illinois, 60637

Other trials in United States

About this study

Official title: Phase I Study to Assess the Tolerability and Efficacy of Nivolumab as Single Agent to Eliminate Minimal Residual Disease and Maintain Remission in Patients With Hematologic Malignancies After Allogeneic Stem Cell Transplantation

This is an open-label, dose escalation Phase I study to evaluate the tolerability and efficacy of single agent of Nivolumab as maintenance treatment to prevent relapse in patients with hematologic malignancies after allogeneic stem cell transplantation. Approximately 29 patients will be enrolled, where about 6-12 patients will be included on the dose escalation phase and 20 patients will be on the expansion cohort at maximal tolerated dose.

Read the detailed description

Nivolumab will be administrated intravenously. Standard dose escalation will be used for the intensification phase with starting dose at 1m/kg every 2 weeks for 4 doses. The DLT observation period is 29 days starting with the first dose taken on Day 1, The study treatment will continue until one of the discontinuation criteria is met. Each dose level (1-2) will be tested using the 3+3 design. If level 2 of 3mg/kg is reached without DLTs, 3mg/kg will be used for the dose expansion cohort. After the intensification phase, patients will start Nivolumab every 12 weeks maintenance phase till 2 years post allo-SCT. Patients will also receive best supportive care (BSC), including blood product transfusions, antimicrobials, and (as appropriate) granulocyte colony stimulating factors for neutropenic infection or poor graft function.

Conditions: Hematologic Malignancies
Being tested: Nivolumab
Keywords: hematologic malignancies, allogeneic stem cell transplantation (allo-SCT)
Medical subject headings: Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NivolumabDrug
Also called Opdivo
Nivolumab dose escalation will be used for the intensification phase with starting dose at 1m/kg every 2 weeks for 4 doses.

Study groups in NCT02985554
Study group	Role	What they receive
Nivolumab	Experimental	Nivolumab will be administrated intravenously. Standard dose escalation will be used for the intensification phase with starting dose at 1m/kg every 2 weeks for 4 doses. Receives: Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum tolerated dose of Nivolumab
The maximum tolerated dose (MTD) of Nivolumab in patients with hematologic malignancies after allo-SCT.
Measured: 24 months

Secondary outcomes (4)

Number of type of adverse events
To evaluate the toxicities of Nivolumab as maintenance treatment after allogeneic stem cell transplantation (allo-SCT).
Measured: 24 months
Incidence of non-relapse mortality
Measured: From the date of therapy to the date of non-relapse death, whichever came first, assessed up to 100 months
Time until progression free survival
Measured: From start date of therapy to the first documented disease relapse or death from any cause, whichever may come first, assessed up to 100 months
Time until overall survival
Measured: From start date of therapy to death from any cause, whichever may come first, assessed up to 100 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Mar 201722 Jun 2020

First posted7 Dec 2016 (estimated)
Study start20 Mar 2017
Primary completion6 Feb 2019
Study completion22 Jun 2020

Why it stopped: Study stopped early due to slow accrual and safety concerns.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Hematologic MalignanciesStudies of the same condition, open and under way.
More trials run by University of ChicagoThe 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 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 3 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02985554
Sponsor's protocol ID: IRB16-0888
Status last verified: Jun 2020
First submitted: 1 Dec 2016
Last updated: 25 Jun 2020
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hematologic Malignancies trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Study to Assess the Tolerability and Efficacy of Nivolumab as Single Agent to Eliminate Minimal Residual Disease and Maintain Remission in Patients With Hematologic Malignancies After Allogeneic Stem Cell Transplantation
ClinicalTrials.gov ID: NCT02985554
Acronym / sponsor ID: IRB16-0888
Conditions: Hematologic Malignancies
Keywords: hematologic malignancies, allogeneic stem cell transplantation (allo-SCT)
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study stopped early due to slow accrual and safety concerns.
Enrolment: 3 participants (actual)
Lead sponsor: University of ChicagoUniversity, hospital or other
Study start: 20 Mar 2017 (actual)
Primary completion: 6 Feb 2019 (actual)
Study completion: 22 Jun 2020 (actual)
First posted: 7 Dec 2016 (estimated)
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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Nivolumab	Experimental	Drug: NivolumabNivolumab will be administrated intravenously. Standard dose escalation will be used for the intensification phase with starting dose at 1m/kg every 2 weeks for 4 doses.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Patients with hematologic malignancies status post allogeneic SCT without evidence of disease relapse, active GVHD or history of more than Stage I skin acute GVHD; and off immunosuppression for at least 4 weeks. At least 60 days after allo-SCT.
Patients with high risk myeloid or lymphoid malignancies at stem cell transplant following ASBMT criteria (http://www.asbmt.org/displaycommon.cfm?an=1\&subarticlenbr=35, under disease classification), including but not limited to conditions listed. Refractory acute myelogenous or lymphoid leukemia Relapsed acute myelogenous or lymphoid leukemia Myelodysplastic syndromes with 5% or more blasts Chronic myelogenous leukemia in chronic phase 3 or more, blast phase presently, or second accelerated phase, Recurrent or refractory malignant lymphoma or Hodgkin's disease with less than a partial response at transplant High risk chronic lymphocytic leukemia defined as no response or stable disease to the most recent treatment regimen.
Age ≥18 years. Because no dosing or adverse event data are currently available on the use of nivolumab in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
ECOG/Karnofsky performance status of 0 or 1 (Karnofsky ≥70%, see Appendix A).
Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to treatment.

Key exclusion criteria (19 listed)

History of allergy to study drug components.
Patients who have disease relapse, active GVHD or history of more than Stage 1 skin acute GVHD, history of cGVHD.
Patients with active infection, un-resolving more than grade 2 transplant-related toxicities.
Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier.
Patients who are receiving any other investigational agents.

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: OpdivoNivolumab dose escalation will be used for the intensification phase with starting dose at 1m/kg every 2 weeks for 4 doses.	Drug	Nivolumab

Primary outcome

Maximum tolerated dose of Nivolumab
Time frame: 24 months
The maximum tolerated dose (MTD) of Nivolumab in patients with hematologic malignancies after allo-SCT.

4 secondary outcomes

Number of type of adverse events
Time frame: 24 months
Incidence of non-relapse mortality
Time frame: From the date of therapy to the date of non-relapse death, whichever came first, assessed up to 100 months
Time until progression free survival
Time frame: From start date of therapy to the first documented disease relapse or death from any cause, whichever may come first, assessed up to 100 months
Time until overall survival
Time frame: From start date of therapy to death from any cause, whichever may come first, assessed up to 100 months

Results and safety

The study was stopped early (reason given: Study stopped early due to slow accrual and safety concerns.). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2020.

Related trials for Hematologic Malignancies

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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.

Hongtao Liu, MD principal investigator

University of Chicago

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Nivolumab in people with Hematologic Malignancies, run by University of Chicago 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 14 inclusion and 19 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: stopped early, as of the sponsor's last update on 25 Jun 2020. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study stopped early due to slow accrual and safety concerns.). Results are not available in the source record.

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?

Maximum tolerated dose of Nivolumab (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02985554.

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 25 Jun 2020.