Acute Myeloid Leukemia Arising From Previous Myelodysplastic SyndromePhase 2NCT02532231
Nivolumab in AML in Remission at High Risk for Relapse
A Phase 2 study testing Laboratory Biomarker Analysis and Nivolumab in people with Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome and Adult Acute Myeloid Leukemia in Remission, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies how well nivolumab works in treating patients with acute myeloid leukemia that has decreased or disappeared but may still be in the body (remission), and is at high risk for returning (relapse). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Adult Acute Myeloid Leukemia in Remission, Blasts Under 10 Percent of Bone Marrow Nucleated Cells
- What is being tested?
- Laboratory Biomarker Analysis and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Oct 2015to 8 Aug 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 AML in remission (defined as CR, CR with incomplete platelet recovery -CRp-, CR with incomplete hematologic recovery -CRi-, or partial remission defined as a bone marrow with < 10% blasts after therapy with or without hematologic recovery)
- High risk for relapse defined as: 1st CR with high risk features for relapse (including history of prior malignancy treated with chemotherapy or radiotherapy, or history of myelodysplastic syndrome, myeloproliferative disorder, chronic myelomonocytic leukemia, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN] or other hematologic malignancy thought to have evolved to AML [i.e., secondary AML, (sAML)]; high risk cytogenetics at diagnosis; fms-related tyrosine kinase 3 [FLT3] mutated at diagnosis; or presence or minimal residual disease assessed by polymerase chain reaction [PCR], cytogenetics, and/or flow cytometry at time of enrollment) 2nd CR regardless of disease characteristics at the time of diagnosis
- Have received induction chemotherapy and at least one cycle of consolidation chemotherapy; patients should have achieved a CR within 12 months of enrollment onto protocol
- No further chemotherapy or stem cell transplant (SCT) planned at the time of enrollment
- Creatinine =< 1.5 x upper limit of normal (ULN)
- Serum bilirubin =< 1.5 x ULN
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- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (b-hCG) pregnancy test result within 24 hours prior to the first dose of treatment and must agree to use an effective contraception method during the study and for 23 weeks after the last dose of the study drug; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy
- Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 31 weeks following the last dose of study drug
- Patients or their legally authorized representative must provide written informed consent
Who cannot join
- History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years; patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses)
- Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 2 weeks prior to the first dose of the study drugs
- Patients with any other known concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes; cardiovascular disease including congestive heart failure New York Heart Association [NYHA] class III or IV, myocardial infarction within 6 months, and poorly controlled hypertension; chronic renal failure; or active uncontrolled infection) which, in the opinion of the investigator could compromise participation in the study
- Patients unwilling or unable to comply with the protocol
- Patients who are on steroids (> 10 mg/day or equivalent) or immune suppression medications
- Patients with autoimmune diseases (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis])
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- Patients with a history of inflammatory bowel disease such as Crohn's disease and ulcerative colitis
- Patients known to be positive for hepatitis B surface antigen expression or with active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months), or with known human immunodeficiency virus (HIV) infection
- Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational agents
- Females who are pregnant or lactating
- Patients with history of previous immunomodulatory therapy (not including lenalidomide or thalidomide)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: PD-1 Inhibition With Nivolumab for the Treatment of Patients With Acute Myeloid Leukemia in Remission at High Risk for Relapse
This phase II trial studies how well nivolumab works in treating patients with acute myeloid leukemia that has decreased or disappeared but may still be in the body (remission), and is at high risk for returning (relapse). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the anti-leukemic effects of nivolumab in patients with acute myeloid leukemia (AML) who have achieved a 1st complete remission (CR) after induction chemotherapy and consolidation chemotherapy and have high risk for relapse, or have achieved a 2nd CR.
SECONDARY OBJECTIVES:
- To evaluate the immunologic responses to nivolumab among patients with AML in CR status post standard chemotherapy.
II. To determine whether response to nivolumab correlates with immunologic responses.
III. To evaluate assessment of minimal residual disease (MRD) by flow cytometry as a predictor of response to immune therapy in treatment of AML and changes during the course of therapy with nivolumab.
IV. To evaluate time to relapse and overall survival. V. To evaluate the toxicity profile of nivolumab among patients with AML in CR.
OUTLINE:
Patients receive nivolumab intravenously (IV) over 1 hour on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After cycle 6, patients may receive nivolumab on day 1 only. After cycle 12, patients may receive nivolumab on day 1 of every 3 cycles. Patients experiencing disease progression may go back to receiving treatment on days 1 and 15 of each cycle.
After completion of study treatment, patients are followed up for 30 days.
- Conditions
- Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Adult Acute Myeloid Leukemia in Remission, Blasts Under 10 Percent of Bone Marrow Nucleated Cells, Therapy-Related Myeloid Neoplasm
- Being tested
- Laboratory Biomarker Analysis, Nivolumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
NivolumabBiological
Also called BMS-936558, MDX-1106, NIVO, ONO-4538
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (nivolumab) | Experimental | Patients receive nivolumab IV over 1 hour on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After cycle 6, patients may receive nivolumab on day 1 only. After cycle 12, patients may receive nivolumab on day 1 of every 3 cycles. Patients experiencing disease progression may go back to receiving treatment on days 1 and 15 of each cycle. Receives: Other: Laboratory Biomarker Analysis; Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence-free Survival Rate
Time from date of treatment start until the date of first objective documentation of disease-relapse.
Measured: Up to 7 years 9 months
Secondary outcomes (4)
Number of Participants With Immunologic Responses to Nivolumab Among Patients With Acute Myeloid Leukemia (AML) in Complete Remission (CR) Status Post Standard Chemotherapy
Participants with Immunologic responses to nivolumab among patients with acute myeloid leukemia (AML) in complete remission (CR) status post standard chemotherapy. CR is Neutrophil count >/= 1.0 x 10^9/L, with a platelet count of >/+ x 10 ^ 9/L
Measured: Every 2 cycles (+/-1 cycle) for the first 6 cycles, then every 3 months while on study, then as clinically indicated till relapse; up to 7 years, 9 months.
Number of Participants Who Changed From MRD Postive to MRD Negative During Therapy With Nibolumab
Assessed by flow cytometry as a predictor of response to immune therapy in treatment of AML. The number of participants who were MRD Positive at the start of therapy with nivolumab and changed to MRD Negative during treatment.
Measured: Every 2 cycles (+/-1 cycle) for the first 6 cycles, then every 3 months while on study, then as clinically indicated till relapse; up to 7 years, 9 months.
Time to Relapse
Time from date of treatment start until the date of first objective documentation of disease-relapse.
Measured: Up to 7 years 9 months
Overall Survival
Time from date of treatment start until date of death due to any cause or last Follow-up.
Measured: Up to 7 years 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2015 (estimated)
- Study start19 Oct 2015
- Primary completion8 Aug 2023
- Study completion8 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia Arising From Previous Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Tapan M Kadia, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02532231
- Sponsor's protocol ID
- 2015-0213
- Other IDs
- NCI-2015-01522, 2015-0213, P30CA016672
- Status last verified
- Oct 2024
- First submitted
- 21 Aug 2015
- Last updated
- 24 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Shallis RM, Podoltsev NA. Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. Curr Opin Hematol. 2021 Mar 1;28(2):110-121. doi: 10.1097/MOH.0000000000000637.
PubMed 33394722
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PD-1 Inhibition With Nivolumab for the Treatment of Patients With Acute Myeloid Leukemia in Remission at High Risk for Relapse
- ClinicalTrials.gov ID
- NCT02532231
- Acronym / sponsor ID
- 2015-0213
- Conditions
- Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Adult Acute Myeloid Leukemia in Remission, Blasts Under 10 Percent of Bone Marrow Nucleated Cells, Therapy-Related Myeloid Neoplasm
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 19 Oct 2015 (actual)
- Primary completion
- 8 Aug 2023 (actual)
- Study completion
- 8 Aug 2023 (actual)
- First posted
- 25 Aug 2015 (estimated)
- Results
- Posted 24 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well nivolumab works in treating patients with acute myeloid leukemia that has decreased or disappeared but may still be in the body (remission), and is at high risk for returning (relapse). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the anti-leukemic effects of nivolumab in patients with acute myeloid leukemia (AML) who have achieved a 1st complete remission (CR) after induction chemotherapy and consolidation chemotherapy and have high risk for relapse, or have achieved a 2nd CR.
SECONDARY OBJECTIVES:
- To evaluate the immunologic responses to nivolumab among patients with AML in CR status post standard chemotherapy.
II. To determine whether response to nivolumab correlates with immunologic responses.
III. To evaluate assessment of minimal residual disease (MRD) by flow cytometry as a predictor of response to immune therapy in treatment of AML and changes during the course of therapy with nivolumab.
IV. To evaluate time to relapse and overall survival. V. To evaluate the toxicity profile of nivolumab among patients with AML in CR.
OUTLINE:
Patients receive nivolumab intravenously (IV) over 1 hour on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After cycle 6, patients may receive nivolumab on day 1 only. After cycle 12, patients may receive nivolumab on day 1 of every 3 cycles. Patients experiencing disease progression may go back to receiving treatment on days 1 and 15 of each cycle.
After completion of study treatment, patients are followed up for 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (nivolumab) | Experimental | Other: Laboratory Biomarker Analysis, Biological: NivolumabPatients receive nivolumab IV over 1 hour on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After cycle 6, patients may receive nivolumab on day 1 only. After cycle 12, patients may receive nivolumab on day 1 of every 3 cycles. Patients experiencing disease progression may go back to receiving treatment on days 1 and 15 of each cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with AML in remission (defined as CR, CR with incomplete platelet recovery -CRp-, CR with incomplete hematologic recovery -CRi-, or partial remission defined as a bone marrow with < 10% blasts after therapy with or without hematologic recovery)
- High risk for relapse defined as: 1st CR with high risk features for relapse (including history of prior malignancy treated with chemotherapy or radiotherapy, or history of myelodysplastic syndrome, myeloproliferative disorder, chronic myelomonocytic leukemia, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN] or other hematologic malignancy thought to have evolved to AML [i.e., secondary AML, (sAML)]; high risk cytogenetics at diagnosis; fms-related tyrosine kinase 3 [FLT3] mutated at diagnosis; or presence or minimal residual disease assessed by polymerase chain reaction [PCR], cytogenetics, and/or flow cytometry at time of enrollment) 2nd CR regardless of disease characteristics at the time of diagnosis
- Have received induction chemotherapy and at least one cycle of consolidation chemotherapy; patients should have achieved a CR within 12 months of enrollment onto protocol
- No further chemotherapy or stem cell transplant (SCT) planned at the time of enrollment
- Creatinine =< 1.5 x upper limit of normal (ULN)
Key exclusion criteria (11 listed)
- History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years; patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses)
- Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 2 weeks prior to the first dose of the study drugs
- Patients with any other known concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes; cardiovascular disease including congestive heart failure New York Heart Association [NYHA] class III or IV, myocardial infarction within 6 months, and poorly controlled hypertension; chronic renal failure; or active uncontrolled infection) which, in the opinion of the investigator could compromise participation in the study
- Patients unwilling or unable to comply with the protocol
- Patients who are on steroids (> 10 mg/day or equivalent) or immune suppression medications
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 |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (nivolumab) |
| NivolumabAlso: BMS-936558, MDX-1106, NIVO, ONO-4538Given IV | Biological | Treatment (nivolumab) |
Primary outcome
Recurrence-free Survival Rate
Time frame: Up to 7 years 9 months
Time from date of treatment start until the date of first objective documentation of disease-relapse.
4 secondary outcomes
Number of Participants With Immunologic Responses to Nivolumab Among Patients With Acute Myeloid Leukemia (AML) in Complete Remission (CR) Status Post Standard Chemotherapy
Time frame: Every 2 cycles (+/-1 cycle) for the first 6 cycles, then every 3 months while on study, then as clinically indicated till relapse; up to 7 years, 9 months.
Number of Participants Who Changed From MRD Postive to MRD Negative During Therapy With Nibolumab
Time frame: Every 2 cycles (+/-1 cycle) for the first 6 cycles, then every 3 months while on study, then as clinically indicated till relapse; up to 7 years, 9 months.
Time to Relapse
Time frame: Up to 7 years 9 months
Overall Survival
Time frame: Up to 7 years 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33394722Shallis RM, Podoltsev NA. Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. Curr Opin Hematol. 2021 Mar 1;28(2):110-121. doi: 10.1097/MOH.0000000000000637.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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.
Tapan M Kadia principal investigator
M.D. Anderson Cancer Center
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 Laboratory Biomarker Analysis and Nivolumab in people with Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome and Adult Acute Myeloid Leukemia in Remission, run by M.D. Anderson Cancer Center 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 11 inclusion and 11 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: finished, as of the sponsor's last update on 24 Oct 2024. 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 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?
Yes. Results are posted in the registry (first posted 24 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Recurrence-free Survival Rate (time frame: Up to 7 years 9 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 NCT02532231, which also lists 1 linked publication.
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 24 Oct 2024.