Acute Biphenotypic LeukemiaPhase 2NCT02399917
Lirilumab and Azacitidine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia
A Phase 2 study testing Azacitidine and Lirilumab in people with Acute Biphenotypic Leukemia and Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies the side effects lirilumab and azacitidine and to see how well they work in treating patients with acute myeloid leukemia that has not responded to treatment or has returned after a period of improvement. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Biphenotypic Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Recurrent Acute Myeloid Leukemia
- What is being tested?
- Azacitidine and Lirilumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Apr 2015to 12 Jul 2018
- 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 or biphenotypic or bilineage leukemia who have failed at least one prior therapy; patients with AML should have failed prior therapy or have relapsed after prior therapy
- Patients should not be eligible or able to receive approved therapy of confirmed clinical benefit in this patient population
- Patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) who received therapy for the MDS or CMML and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML; the World Health Organization (WHO) classification will be used for AML
- Prior therapy with hydroxyurea, chemotherapy, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Total bilirubin =< 2 times upper limit of normal (x ULN) (=< 3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome)
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- Aspartate aminotransferase or alanine aminotransferase =< 2.5 x ULN (=< 5.0 x ULN if considered to be due to leukemic involvement)
- Serum creatinine =< 2 x ULN or glomerular filtration rate (GFR) >= 50
- Patients must provide written informed consent
- In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of 5-azacytidine and lirilumab will be at least 2 weeks OR at least 5 half-lives for cytotoxic/noncytotoxic agents; use of one dose of cytarabine (up to 2 g/m^2) is allowed prior to the start of study therapy or hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and while the patient is on active study treatment, as needed, for clinical benefit and after discussion with the principal investigator (PI); concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted
- Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment
- Women of childbearing potential must agree to use an adequate method of contraception during the study and until 30 days after the last treatment; males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 30 days after the last treatment; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
Who cannot join
- Patients with known allergy or hypersensitivity to lirilumab, 5-azacytidine, or any of their components; patients who have previously been treated with lirilumab in combination with 5-azacytidine will be excluded
- Patients with a known history of severe interstitial lung disease or severe pneumonitis or active pneumonitis that is uncontrolled in the opinion of the treating physician
- Patients with a known history of any of the following autoimmune diseases are excluded: (a) patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) (b) patients with a history of rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis])
- Patients with organ allografts (such as renal transplant) are excluded
- Patients with allogeneic stem cell transplantation within the last 6 months or patients with active graft-versus-host disease (GVHD) will be excluded
- Ongoing immunosuppressive therapy, including cyclosporine and tacrolimus; patients who are on high dose steroid; Note: Subjects may be using systemic corticosteroids (daily doses =< 10 mg of prednisone or equivalent) or topical or inhaled corticosteroids
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- Patients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemia
- Active and uncontrolled disease/(active uncontrolled infection, uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure New York Heart Association [NYHA] class III/IV, clinically significant and uncontrolled arrhythmia) as judged by the treating physician
- Patients with active and uncontrolled human immunodeficiency virus (HIV) infection will be excluded; however, patients with well controlled HIV infection will be considered
- Patients known to be positive for hepatitis B by surface antigen expression; known to have active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months)
- Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator
- Patients unwilling or unable to comply with the protocol
- Pregnant or breastfeeding
- Acute promyelocytic leukemia (APL)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label Phase II Study of Lirilumab (BMS-986015) in Combination With 5-Azacytidine (Vidaza) for the Treatment of Patients With Refractory/Relapsed Acute Myeloid Leukemia
This phase II trial studies the side effects lirilumab and azacitidine and to see how well they work in treating patients with acute myeloid leukemia that has not responded to treatment or has returned after a period of improvement. Monoclonal antibodies, such as lirilumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving lirilumab with azacitidine may be an effective treatment for relapsed or refractory acute myeloid leukemia.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of lirilumab in combination with 5-azacytidine (azacitidine) in patients with refractory/relapsed acute myeloid leukemia (AML). (Part A, Lead-In Phase) II. To determine the overall response rate (ORR) of lirilumab in combination with 5-azacytidine in patients with refractory/relapsed AML. (Part B, Phase II)
SECONDARY OBJECTIVES:
- To determine the duration of response, disease-free survival (DFS), and overall survival (OS) of patients with refractory/relapsed AML treated with this combination.
II. To determine the safety of lirilumab in combination with 5-azacytidine in patients with refractory/relapsed AML.
OUTLINE:
Patients receive azacitidine subcutaneously (SC) or intravenously (IV) over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and up to 90 days.
- Conditions
- Acute Biphenotypic Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- Being tested
- Azacitidine, Lirilumab
- Medical subject headings
- Leukemia, Biphenotypic, Acute, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5 AZA, 5-AC, 5-Azacytidine, 5-AZC
Given SC or IV
LirilumabBiological
Also called BMS-986015, IPH2102
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Phase 1b Lead-in Cohort 1 | Experimental | Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
5-Azacitidine 75mg/m^2 Lirilumab 1.0 mg/kg Receives: Drug: Azacitidine; Biological: Lirilumab |
| Phase 1b Lead-in Cohort 2 | Experimental | Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Receives: Drug: Azacitidine; Biological: Lirilumab |
| Phase 2 | Experimental | Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Receives: Drug: Azacitidine; Biological: Lirilumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose of Iirilumab in Combination With 5-azacitidine
To identify the dose at which <2/6 participants experience Dose Limiting Toxicities (DLT). The dose level at which 0-1/6 participants experience a DLT in the first 28 days of treatment will be the maximum tolerated dose (MTD) and would be used to treat an additional 34 participants in the phase II potion of the study. (Part A, Lead-In Phase)
Measured: Up to 28 days
Participants With an Objective Response
Objective Response Rate (ORR) will be monitored using the Bayesian approach of Thall, Simon, Estey and the extension by Thall and Sung. Overall response rate (ORR), defined as complete remission (CR) + CR with incomplete platelet recovery (CRp) + CR with incomplete count recovery (CRi) + partial response (PR) + marrow clearance of blasts + hematological improvement within 3 months of treatment initiation among adult patients with refractory/relapsed Acute Myelogenous Leukemia (AML) (Phase II)
Measured: Up to 3 months
Secondary outcomes (3)
Duration of Response
The date of Objective Response to the date of loss of response or last follow-up.
Measured: Up to 2.5 years
Overall Survival
Overall Survival (OS) is defined: Time of presentation to date of death or censored at last follow-up date.
Measured: Up to 2 years
Disease Free Survival
Disease Free Survival (DFS) is defined: Time from date of treatment start until the date of first objective documentation of disease-relapse
Measured: Up to 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2015 (estimated)
- Study start20 Apr 2015
- Primary completion12 Jul 2018
- Study completion12 Jul 2018
Why it stopped: This study was terminated early due to response rates not meeting the anticipated minimum of 30%.
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.
- Other trials for Acute Biphenotypic LeukemiaStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Phase IB, lead-in/II to determine MTD
- Masking
- None (open label)
- Enrolment
- 36 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
- Naval Daver, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02399917
- Sponsor's protocol ID
- 2014-0862
- Other IDs
- NCI-2015-00678, 2014-0862, P30CA016672
- Status last verified
- Sep 2019
- First submitted
- 23 Mar 2015
- Last updated
- 24 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Phase II Study of Lirilumab (BMS-986015) in Combination With 5-Azacytidine (Vidaza) for the Treatment of Patients With Refractory/Relapsed Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT02399917
- Acronym / sponsor ID
- 2014-0862
- Conditions
- Acute Biphenotypic Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated early due to response rates not meeting the anticipated minimum of 30%.
- Enrolment
- 36 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 20 Apr 2015 (actual)
- Primary completion
- 12 Jul 2018 (actual)
- Study completion
- 12 Jul 2018 (actual)
- First posted
- 26 Mar 2015 (estimated)
- Results
- Posted 24 Sep 2019
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 the side effects lirilumab and azacitidine and to see how well they work in treating patients with acute myeloid leukemia that has not responded to treatment or has returned after a period of improvement. Monoclonal antibodies, such as lirilumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving lirilumab with azacitidine may be an effective treatment for relapsed or refractory acute myeloid leukemia.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of lirilumab in combination with 5-azacytidine (azacitidine) in patients with refractory/relapsed acute myeloid leukemia (AML). (Part A, Lead-In Phase) II. To determine the overall response rate (ORR) of lirilumab in combination with 5-azacytidine in patients with refractory/relapsed AML. (Part B, Phase II)
SECONDARY OBJECTIVES:
- To determine the duration of response, disease-free survival (DFS), and overall survival (OS) of patients with refractory/relapsed AML treated with this combination.
II. To determine the safety of lirilumab in combination with 5-azacytidine in patients with refractory/relapsed AML.
OUTLINE:
Patients receive azacitidine subcutaneously (SC) or intravenously (IV) over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and up to 90 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Phase IB, lead-in/II to determine MTD
| Arm | Type | Receives |
|---|---|---|
| Phase 1b Lead-in Cohort 1 | Experimental | Drug: Azacitidine, Biological: LirilumabPatients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 1.0 mg/kg |
| Phase 1b Lead-in Cohort 2 | Experimental | Drug: Azacitidine, Biological: LirilumabPatients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg |
| Phase 2 | Experimental | Drug: Azacitidine, Biological: LirilumabPatients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients with AML or biphenotypic or bilineage leukemia who have failed at least one prior therapy; patients with AML should have failed prior therapy or have relapsed after prior therapy
- Patients should not be eligible or able to receive approved therapy of confirmed clinical benefit in this patient population
- Patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) who received therapy for the MDS or CMML and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML; the World Health Organization (WHO) classification will be used for AML
- Prior therapy with hydroxyurea, chemotherapy, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Key exclusion criteria (14 listed)
- Patients with known allergy or hypersensitivity to lirilumab, 5-azacytidine, or any of their components; patients who have previously been treated with lirilumab in combination with 5-azacytidine will be excluded
- Patients with a known history of severe interstitial lung disease or severe pneumonitis or active pneumonitis that is uncontrolled in the opinion of the treating physician
- Patients with a known history of any of the following autoimmune diseases are excluded: (a) patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) (b) patients with a history of rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis])
- Patients with organ allografts (such as renal transplant) are excluded
- Patients with allogeneic stem cell transplantation within the last 6 months or patients with active graft-versus-host disease (GVHD) will be excluded
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 |
|---|---|---|
| AzacitidineAlso: 5 AZA, 5-AC, 5-Azacytidine, 5-AZCGiven SC or IV | Drug | Phase 1b Lead-in Cohort 1, Phase 1b Lead-in Cohort 2, Phase 2 |
| LirilumabAlso: BMS-986015, IPH2102Given IV | Biological | Phase 1b Lead-in Cohort 1, Phase 1b Lead-in Cohort 2, Phase 2 |
Primary outcome
Maximum Tolerated Dose of Iirilumab in Combination With 5-azacitidine
Time frame: Up to 28 days
To identify the dose at which <2/6 participants experience Dose Limiting Toxicities (DLT). The dose level at which 0-1/6 participants experience a DLT in the first 28 days of treatment will be the maximum tolerated dose (MTD) and would be used to treat an additional 34 participants in the phase II potion of the study. (Part A, Lead-In Phase)
Participants With an Objective Response
Time frame: Up to 3 months
Objective Response Rate (ORR) will be monitored using the Bayesian approach of Thall, Simon, Estey and the extension by Thall and Sung. Overall response rate (ORR), defined as complete remission (CR) + CR with incomplete platelet recovery (CRp) + CR with incomplete count recovery (CRi) + partial response (PR) + marrow clearance of blasts + hematological improvement within 3 months of treatment initiation among adult patients with refractory/relapsed Acute Myelogenous Leukemia (AML) (Phase II)
3 secondary outcomes
Duration of Response
Time frame: Up to 2.5 years
Overall Survival
Time frame: Up to 2 years
Disease Free Survival
Time frame: Up to 2.5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Naval Daver 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 Azacitidine and Lirilumab in people with Acute Biphenotypic Leukemia and Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, 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 12 inclusion and 14 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 24 Sep 2019. 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 Sep 2019). 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?
Maximum Tolerated Dose of Iirilumab in Combination With 5-azacitidine (time frame: Up to 28 days). 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 24 Sep 2019.