Pembrolizumab and Decitabine for Refractory or Relapsed Acute Myeloid Leukemia

Phase 1

Completed

Conditions: Relapsed Acute Myeloid Leukemia

Interventions: Drug: Pembrolizumab
Drug: Decitabine

Registration Number: NCT02996474

Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

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.

Detailed Description: This is a pilot study to determine the feasibility of a novel combination of Pembrolizumab and Decitabine in relapsed/refractory adult AML patients. While both Pembrolizumab and Decitabine are FDA approved agents, this study will explore giving these drugs in combination for this population of patients.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pembrolizumab and Decitabine for treatment of Acute Myeloid Leukemia	Pembrolizumab	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.
Pembrolizumab and Decitabine for treatment of Acute Myeloid Leukemia	Decitabine	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.

Primary Outcome Measures

Name	Time	Method
Feasibility of a Novel Combination of Pembrolizumab and Decitabine in Relapsed/Refractory Acute Myeloid Leukemia Participants	24 weeks	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.

Secondary Outcome Measures

Name	Time	Method
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)	Time to first response (days) is time from start of study to first response (mCR, mCRi, CR, CRi, PR, or SD) in relapsed/refractory acute myeloid leukemia (AML) participants. Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, \< 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, \< 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be \< 1,000/mcl and/or platelet count \< 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count \> 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts \< 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.
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)	Time to Best Response is defined as time (days) from start of study to initial achievement of best response. Best response is defined by the order of mCR, mCRi, CR, CRi, PR, or SD. Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, \< 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, \< 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be \< 1,000/mcl and/or platelet count \< 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count \> 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts \< 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.
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)	To determine duration (days) of response as defined as time from initial achievement of response to loss of response (mCR, mCRi, CR, CRi, PR, or SD). Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, \< 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, \< 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be \< 1,000/mcl and/or platelet count \< 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count \> 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts \< 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.
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)	Duration of Best Response is time (days) from initial achievement of best response to loss of best response. Best response is defined by the order of mCR, mCRi, CR, CRi, PR, or SD. Measurable residual disease (MRD) negative complete remission is no evidence of residual disease, \< 5% blasts, no Auer rods and may be with mCR or without count recovery (ANC ≥ 1,000/mcl and platelet count ≥ 100,000/mcl) as mCRi. Morphologic complete remission (CR) is ANC ≥ 1,000/mcl, platelet count ≥ 100,000/mcl, \< 5% blasts, no Auer rods, no evidence of disease; Morphologic complete remission with incomplete blood count recovery (CRi) is same as CR but ANC may be \< 1,000/mcl and/or platelet count \< 100,000/mcl; Partial remission (PR) is ANC ≥ 1,000/mcl, platelet count \> 100,000/mcl, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts \< 5% with persistent Auer rods. Stable disease (SD) is absence of a complete or partial response, and no progressive disease.
Overall Survival	from enrollment until date of death, assessed up to 24 weeks	Number of participants overall survival is defined as death from any cause