Pembrolizumab and Decitabine for Refractory or Relapsed Acute Myeloid Leukemia

NCT02996474 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 17002617-H-0026
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Acute myeloid leukemia (AML) is a cancer of the white blood cells. It is fatal if not treated. Treatment for AML that has not responded to treatment (refractory) or has returned after treatment (relapsed) often do not work. Researchers want to see if an immunotherapy drug, combined with a less intense chemotherapy, may be able to help. Objective: To test if pembrolizumab, in combination with decitabine, is a possible treatment for people with relapsed or refractory AML. Eligibility: Adults 18 years of age and older with refractory AML or relapsed AML. Design: Participants will be first screened for eligibility. The study is counted in 21-day cycles. The initial phase of the study consists of 8 cycles. Participants may be in the study for up to 2 years if they are responding to the treatment. The first 3 weeks of treatment is usually done in the hospital. The rest may be done as an outpatient. Participants will get pembrolizumab at the beginning of each cycle through an IV. Participants will usually get decitabine by IV on days 8 12 and days 15 19 of every other cycle. Participants will give blood samples. Participants will have bone marrow exams. A needle will be inserted into the hip to extract cells from the bone marrow. Some participants may give a sample of saliva from the inside of their cheek. Some participants may give a small skin sample. The top layer of the skin is removed. Some patients may require leukapheresis before starting treatment. This is a procedure to remove leukemia cells in the blood stream.

Conditions

Relapsed Acute Myeloid Leukemia

Keywords

Pembrolizumab; Decitabine; AML (Acute Myelogenous Leukemia)

Outcome Measures

Primary Outcomes (1)

• Feasibility of a Novel Combination of Pembrolizumab and Decitabine in Relapsed/Refractory Acute Myeloid Leukemia Participants

  The number of patients who could be treated with a novel combination of Pembrolizumab and Decitabine in relapsed/refractory Acute Myeloid Leukemia participants without being removed from the protocol due to treatment related toxicities.

  24 weeks

Secondary Outcomes (5)

• Median Days to First Response From Start of Study to Initial Achievement of First Response (mCR, mCRi, CR, CRi, PR, or SD)

  At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)

• Median Days to Best Response From Start of Study to Initial Achievement of Best Response (by the Order of mCR, mCRi, CR, CRi, PR, or SD)

  At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)

• Median Duration (Days) of Response From Initial Achievement of Response to Loss of Response (mCR, mCRi, CR, CRi, PR, or SD)

  At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)

• Median Duration (Days) of Best Response From Initial Achievement of Best Response to Loss of Best Response (by the Order of mCR, mCRi, CR, CRi, PR, or SD)

  At the end of each cycle 2 (week 6), 4 (week 12), 6 (week 18), 8 (up to week 24)

• Overall Survival

  from enrollment until date of death, assessed up to 24 weeks

Study Arms (1)

Pembrolizumab and Decitabine for treatment of Acute Myeloid Leukemia

EXPERIMENTAL

Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Up to eight cycles of pembrolizumab will be given during the initial induction phase. Each cycle is 21 days. Decitabine will be administered at a dose of 20 mg/m\^2 by intravenous infusion over approximately 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7) for treatment relapsed/refractory AML.

Drug: Pembrolizumab; Drug: Decitabine

Interventions

Pembrolizumab DRUG

200 mg will be administered as a 30 minute IV infusion every 3 weeks. Every effort should be made to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min).

Also known as: Keytruda, MK-3475

Pembrolizumab and Decitabine for treatment of Acute Myeloid Leukemia

Decitabine DRUG

Will be administered at a dose of 20 mg/m\^2 by continuous intravenous infusion over 1 hour repeated daily ordinarily on days 8 through 12 and 15 through 19 of alternative cycles (ie: cycles 1, 3, 5, 7). Decitabine should be repeated every 6 weeks.

Also known as: Dacogen

Pembrolizumab and Decitabine for treatment of Acute Myeloid Leukemia

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Unequivocal diagnosis of relapsed or refractory acute myeloid leukemia (AML) confirmed by an NIH attending pathologist within 30 days of study enrollment (includes residual AML as confirmed by institutional standards by NIH pathologists
• Received at least one prior AML therapy before study enrollment.
• Ability to comprehend the investigational nature of the study and provide informed consent.
• Be at least 18 years of age on day of signing informed consent.
• Availability of a physician willing to assume clinical care after completion of the study.
• Be willing to provide blood and bone marrow for research as described in the study.
• Have a performance status of less than or equal to 1 on the ECOG Performance Scale
• Demonstrate adequate organ function as defined below, all screening labs should be performed within 14 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 must be willing to use an adequate method of contraception; 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 must 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. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Adequate Organ Function Laboratory Values: System Laboratory - Value
• Renal
• Serum Creatinine - Less than or equal to 1.5 X upper limit of normal (ULN)
• Hepatic

You may not qualify if:

• The subject must be excluded from participating in the trial if the subject:
• Has a diagnosis of acute promyelocytic leukemia (APL)
• Has previously received an allogeneic hematopoietic stem cell transplant.
• Has received AML treatment with an investigational therapy or 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 hypersensitivity to pembrolizumab or any of its excipients.
• Has hypersensitivity to decitabine or any of its excipients.
• Has received more than two prior cycles of decitabine.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1.
• Note: Subjects who have received cytoreductive therapy with hydroxyurea at any time prior to study Day 1 are an exception to this criterion.
• Has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to previously administered AML therapy agents.
• Note: Subjects with less than or equal to Grade 2 neuropathy are an exception 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.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Goswami M, Gui G, Dillon LW, Lindblad KE, Thompson J, Valdez J, Kim DY, Ghannam JY, Oetjen KA, Destefano CB, Smith DM, Tekleab H, Li Y, Dagur P, Hughes T, Marte JL, Del Rivero J, Klubo-Gwiezdzinksa J, Gulley JL, Calvo KR, Lai C, Hourigan CS. Pembrolizumab and decitabine for refractory or relapsed acute myeloid leukemia. J Immunother Cancer. 2022 Jan;10(1):e003392. doi: 10.1136/jitc-2021-003392.

  PMID: 35017151 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

pembrolizumab; Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

The 5 patients who did not complete the study were for reason other than treatment related toxicities.

Results Point of Contact

• Title: Christopher Hourigan
• Organization: National Heart Lung and Blood Institute

christopher.hourigan@nih.gov

+1 301 451 0257

Study Officials

• Christopher S Hourigan, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2016
• First Posted: December 19, 2016
• Study Start: December 16, 2016
• Primary Completion: April 2, 2019
• Study Completion: April 2, 2019
• Last Updated: December 28, 2022
• Results First Posted: May 21, 2020

Record last verified: 2019-11-20

Locations

US (1)