Azacitidine and Pembrolizumab in Treating Patients With Myelodysplastic Syndrome

NCT03094637 | Unknown Phase 2 Results FDA Drug

• 2 other identifiers: 2016-0343NCI-2018-01238
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the side effects of azacitidine and pembrolizumab and to see how well they work in treating patients with myelodysplastic syndrome. Azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving azacitidine and pembrolizumab may work better at treating myelodysplastic syndrome.

Conditions

High Risk Myelodysplastic Syndrome; IPSS Risk Category Intermediate-1; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (3)

• Overall Response Rate (ORR) Defined as Complete Response + Partial Response + Hematological Improvement

  Will estimate the ORR for the experimental treatments, along with the 95% credible intervals. The association between ORR and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.

  Up to 2 years 4 months

• Event Free Survival

  Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.

  Up to 4 years

• Overall Survival

  Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests. Overall Survival will be presented by median survival, which is the time point at which the cumulative survival drops below 50%. If there is no median survival (not reached), it means the cumulative survival was more than 50%.

  Up to 4 years

Study Arms (1)

Treatment (azacitidine, pembrolizumab)

EXPERIMENTAL

Patients receive azacitidine Intravenous (IV) over 10-40 minutes or Subcutaneous (SC) on days 1-7, and pembrolizumab IV over 30 minutes every 3 weeks. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine; Biological: Pembrolizumab

Interventions

Azacitidine DRUG

Given IV

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Treatment (azacitidine, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (azacitidine, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary signed informed consent before performance of any study related procedure not part of normal medical care indicating that the patient is aware of the investigation and nature of this study in keeping with institutional policies and with the understanding that the consent may be withdrawn with the subject at any time without prejudice to future medical care
• Intermediate 1 (INT-1) or higher risk MDS defined by International Prognostic Scoring System (IPSS) criteria
• Patients can or cannot have receive prior therapy with hypomethylating agent but will be allocated to specific patient cohorts based on their prior exposure. Patients that had received prior hypomethylating agent therapy should have at least received 6 cycles of therapy and not achieved any response or had progressed after any given number of cycles
• Eastern Cooperative Oncology Group (ECOG) performance of 0 to 2
• Male patients, even if surgically sterilized, should agree to practice effective barrier contraception for the entire study treatment period and through 120 days after the last dose of the study treatment or agree to completely abstain from heterosexual intercourse. Female patients who are postmenopausal for at least one year before the screening visit or are surgical sterile or if they are of child bearing potential must have a negative pregnancy test within 72 hours of treatment of the start date and agree to practice two effective methods of contraception forms at the same time from the time of signing the informed consent through 120 days of the last dose of the study treatment or agree to completely abstain from heterosexual intercourse
• Willingness and ability to comply with scheduled visits treatment plans, laboratory tests and other study procedures
• Serum creatinine or measured or calculated creatine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrcL\]) =\< 2.0 x upper limit of normal (ULN) or \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN (performed within 10 days of treatment initiation). Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =\< 2.0 x ULN (unless considered due to Gilbert's disease or leukemia disease) or direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN (performed within 10 days of treatment initiation)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN (unless considered due to Gilbert's disease or leukemia disease) or =\< 5 x ULN for subjects with liver metastases (performed within 10 days of treatment initiation)
• 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 should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
• Patients must receive a minimum dose of azacitidine of 75mg/(m)(2) dose

You may not qualify if:

• Significant medical psychiatric cognitive or other conditions that may compromise the patient ability to understand the patient information to give informed consent to comply with the study protocol or to complete the study
• Any severe or concurrent disease or condition including uncontrolled systemic infection, congestive heart failure, angina pectoris or cardiac arrhythmia and autoimmune processes that in the opinion of the investigator would make the patient inappropriate for study participation
• Patients with known hypersensitivity to 5-azacitidine or MK3475 or any of their excipients
• Prior history of stem cell transplantation
• For patients in the relapse or refractory cohort, any other therapy not being a hypomethylating agent after hypomethylating agents (HMA) failure or more than 4 months since completion of last cycle of hypomethylating agent. Please note that hypomethylating agent may include second generation compounds such as SGI-110, oral decitabine or oral azacitidine and will also include combinations with investigational agents
• Treatment with other investigational agents including chemotherapy, immunotherapy, or radiation therapy within a month prior to the start of this clinical trial
• 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
• 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)
• 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 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) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has known history of, or any evidence of active, non-infectious pneumonitis

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Azacitidine; pembrolizumab

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Guillermo Garcia-Manero MD/Professor
• Organization: The University of Texas MD Anderson Cancer Center

ggarciam@mdanderson.org

713-745-3428

Study Officials

• Guillermo Garcia-Manero

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2017
• First Posted: March 29, 2017
• Study Start: November 6, 2017
• Primary Completion: November 6, 2021
• Study Completion: November 6, 2023
• Last Updated: March 22, 2023
• Results First Posted: October 1, 2021

Record last verified: 2023-02

Locations

US (1)