AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 2NCT02845297

Study of Azacitidine in Combination With Pembrolizumab in R/R AML Patients and in Newly Diagnosed Older Patients

A Phase 2 study testing pembrolizumab and Azacitadine in people with Acute Myeloid Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a multicenter, nonrandomized, open-label phase 2 study (with a safety run-in phase) of azacitidine (AZA) 75 mg/m2 given IV or SQ on days 1-7 every 28 days in combination with pembrolizumab 200 mg given IV every 3 weeks (starting on day 8 of cycle 1). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
pembrolizumab and Azacitadine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
67 participants
Where
3 sitesUnited States
Study dates
Jul 2016to Dec 2022
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 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Cohort #1
  • Have histologically or cytologically confirmed relapsed or refractory AML (i.e. ≥5% blasts by manual differential on bone marrow aspirate/biopsy/flow cytometry), excluding acute promyelocytic leukemia (APL; FAB M3; t(15;17))
  • Be willing and able to provide written informed consent/assent for the trial.
  • Be > 18 years of age on day of signing informed consent.
  • Not be appropriate candidate for intensive salvage chemotherapy due to co-morbidities or other disease- or treatment-related factors.
  • NOTE: Subjects who received prior treatment with hypomethylating agents either for Myelodysplastic Syndrome (MDS), Myeloproliferative Neoplasm (MPN), or AML will be eligible if they achieved response to hypomethylating agents in the past (PR or CR) and did not progress while receiving therapy with hypomethylating agents.
Show all 35Show fewer
  • NOTE: Subjects who had prior allogeneic stem cell transplant (alloHSCT) will be eligible as long as they have been at least 3 months after allogeneic HSCT and are off of all immune suppression for at least 3 weeks (>21 days) and have no evidence of active graft versus host disease (GVHD). Subjects with prior alloHSCT will NOT be eligible for enrollment during the safety run in phase.
  • Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 14 days of treatment initiation.
  • ECOG performance status ≤ 2.
  • A projected life expectancy of at least 12 weeks.
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female subjects of childbearing potential (Section 5.8.2) must be willing to use an adequate method of contraception as outlined in Section 5.8.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
  • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Male subjects of childbearing potential (Section 5.8.2) must agree to use an adequate method of contraception as outlined in Section 5.8.2- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures for the entire length of the study.
  • Cohort #2
  • Have histologically and cytologically confirmed newly diagnosed AML (i.e. ≥ 20% blasts by manual differential on bone marrow aspirate/biopsy and/or in peripheral blood), excluding acute promyelocytic leukemia (APL; FAB M3, t (15;17))
  • Be willing and able to provide written informed consent/assent for the trial.
  • Be ≥65 years of age on day of signing informed consent.
  • Have received NO prior treatment for AML with the exception of hydroxyurea/leukapheresis.
  • NOTE: Subjects may have been treated for pre-existent myeloid disorder such as Myelodysplastic Syndrome or Myeloproliferative Neoplasm excluding hypomethylating agents.
  • Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 14 days of treatment initiation.
  • ECOG performance status ≤ 2.
  • A projected life expectancy of at least 12 weeks.
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female subjects of childbearing potential (Section 5.8.2) must be willing to use an adequate method of contraception as outlined in Section 5.8.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
  • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Male subjects of childbearing potential (Section 5.8.2) must agree to use an adequate method of contraception as outlined in Section 5.8.2- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures for the entire length of the study.
  • Adequate Organ Function Laboratory Values
  • White blood cell (WBC) count <30,000 /mcL
  • Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN Serum total bilirubin ≤ 1.5 X ULN AST (SGOT) and ALT (SGPT) ≤ 3 X ULN Albumin >2.5 mg/dL International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

Who cannot join

  • Cohort #1
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • NOTE: Subjects who were treated on a clinical study of allogeneic stem cell transplant (alloHSCT) will be eligible if they are at least 3 months after allogeneic HCT and are at least 3 weeks (>21 days) off of all immune suppression and have no evidence of active GVHD (physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency is allowed). Subjects with prior alloHSCT will not be eligible for enrollment during the safety run in phase.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
Show all 47Show fewer
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks or growth factors within 1 week prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has known active central nervous system (CNS) leukemia. Subjects with previously treated CNS leukemia may participate provided that they have documented clearance of CNS leukemia and are not actively treated with intrathecal chemotherapy.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Subjects that require intermittent use of bronchodilators or local steroid injections will not be excluded from the study.
  • Has known history of, or any evidence of active, non-infectious pneumonitis.
  • Has an active uncontrolled infection requiring systemic therapy (viral, bacterial or fungal). Patients with infection under active treatment and controlled with antibiotics are eligible.
  • Has a white blood cell count > 30 x 109/L. NOTE: Leukapheresis and Hydroxyurea is permitted to meet this criterion and should be stopped ≥12 hours before starting treatment on the study.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  • Cohort #2
  • Has received treatment with hypomethylating agent for pre-existent myeloid disorder such Myelodysplastic Syndrome (MDS) or Myeloproliferative Neoplasm (MPN).
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment for pre-existent myeloid disorder such as MDS or MPN.
  • Not be eligible for treatment with a standard cytarabine and anthracycline or similar intensive induction chemotherapy due to co-morbidities or other factors, or is unwilling to receive intensive induction therapy.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks or growth factors within 1 week prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has known active central nervous system (CNS) leukemia. Subjects with previously treated CNS leukemia may participate provided that they have documented clearance of CNS leukemia and are not actively treated with intrathecal chemotherapy.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Subjects that require intermittent use of bronchodilators or local steroid injections will not be excluded from the study.
  • Has known history of, or any evidence of active, non-infectious pneumonitis.
  • Has an active uncontrolled infection requiring systemic therapy (viral, bacterial or fungal). Patients with infection under active treatment and controlled with antibiotics are eligible.
  • Has a white blood cell count > 30 x 109/L. NOTE: Leukapheresis and hydroxyurea is permitted to meet this criterion and should be stopped ≥12 hours before starting treatment on the study.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Johns Hopkins Oncology Center

    Baltimore, Maryland, 21231-2410

  • University of North Carolina Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina Hollings Cancer Center

    Charleston, South Carolina, 29425

Other trials in United States

About this study

Official title: Phase 2 Study of Azacitidine in Combination With Pembrolizumab in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients and in Newly Diagnosed Older (≥65 Years) AML Patients

This is a multicenter, nonrandomized, open-label phase 2 study (with a safety run-in phase) of azacitidine (AZA) 75 mg/m2 given IV or SQ on days 1-7 every 28 days in combination with pembrolizumab 200 mg given IV every 3 weeks (starting on day 8 of cycle 1). The dose/schedule of AZA selected for this study is FDA approved for patients with MDS/AML.

Read the detailed description

Acute myeloid leukemia (AML) remains a therapeutic challenge. Although 60-80% of newly diagnosed patients with AML respond to induction chemotherapy, the relapse rate remains high (40%-50%) even after allogeneic stem cell transplant (alloHSCT). Data suggests that epigenetic therapy with azacitidine combined with blockade of PD-1/PD-L1 pathway is a rational therapeutic approach both in newly diagnosed older patients and those with relapsed and refractory AML. Furthermore, recent data suggest that the addition of PD-1 blockade (nivolumab) to azacitidine in patients with AML who have previously failed hypomethylating agents may induce responses in up to 20% patients

We plan to examine two AML patient cohorts:

Cohort 1: relapsed/refractory AML. Cohort 2: newly diagnosed AML in older patients (≥65 years) not candidates for induction chemotherapy. Azacitidine and pembrolizumab have distinct mechanisms of action with no common overlapping toxicities; however, as azacitidine and pembrolizumab have not been tested previously in combination in AML patients, we plan to start enrollment with Cohort 1 (a safety run-in phase) and include only relapsed/refractory AML patients excluding those relapsing after allogeneic hematopoietic stem cell transplant (alloHSCT). The primary objective of the run in safety phase would be to determine the safe and tolerable dose/schedule of azacitidine and pembrolizumab in patients with AML. We will perform safety run in phase only in Cohort 1 as Cohort 2 patients would be expected to have a same or better tolerability given that they are not heavily pretreated

Being tested
pembrolizumab, Azacitadine
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • pembrolizumabDrug

    Also called MK-3475

    Intravenous pembrolizumab

  • AzacitadineDrug

    Also called Vidaza

    Intravenous or subcutaneous

Study groups in NCT02845297
Study groupRoleWhat they receive
Safety Run In Phase (only Cohort 1):ExperimentalThe treatment of relapsed and refractory AML patients.
Receives: Drug: pembrolizumab; Drug: Azacitadine
Cohort 2ExperimentalThe treatment of newly diagnosed AML patients (≥ 65 years) who are not candidates for intensive induction chemotherapy.
Receives: Drug: pembrolizumab; Drug: Azacitadine

What is being measured

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

  1. Maximal Tolerable Dose of Pembrolizumab for Cohort 1

    The primary objective is to determine the safe and tolerable dose for both the relapsed/refractory AML patients.

    Measured: 3- 28 day cycles

Secondary outcomes (1)

  1. Number of Participants Who Had Complete Remission/Complete Remission With Incomplete Recovery

    Response will be assessed using the International European LeukemiaNet Guidelines in AML63 and IWG Modified Response Criteria (2006) for CR and CRi. CR is bone marrow blasts <5%; absence of circulating blasts; ANC > or = 1, 000/mcL; platelet count > or = 100,000/mcL. CRi is all CR criteria except for residual neutropenia (<1,000/mcL) or thrombocytopenia (<100,000/mcL).

    Measured: 3-28 day cycles

Timeline

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

  1. First posted27 Jul 2016 (estimated)
  2. Study startJul 2016
  3. Primary completionApr 2022
  4. Study completionDec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
67 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02845297
Sponsor's protocol ID
J1651
Other IDs
IRB00098812
Status last verified
Mar 2023
First submitted
18 Jul 2016
Last updated
9 Mar 2023
Data monitoring committee
No
Individual data sharing
No

Publications

  • Rutella S, Vadakekolathu J, Mazziotta F, Reeder S, Yau TO, Mukhopadhyay R, Dickins B, Altmann H, Kramer M, Knaus HA, Blazar BR, Radojcic V, Zeidner JF, Arruda A, Wang B, Abbas HA, Minden MD, Tasian SK, Bornhauser M, Gojo I, Luznik L. Immune dysfunction signatures predict outcomes and define checkpoint blockade-unresponsive microenvironments in acute myeloid leukemia. J Clin Invest. 2022 Nov 1;132(21):e159579. doi: 10.1172/JCI159579.

    PubMed 36099049

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing pembrolizumab and Azacitadine in people with Acute Myeloid Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 3 sites 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 35 inclusion and 47 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 9 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 1 Mar 2023). 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?

Maximal Tolerable Dose of Pembrolizumab for Cohort 1 (time frame: 3- 28 day cycles). 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 NCT02845297, 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 9 Mar 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in