B Acute Lymphoblastic LeukemiaPhase 2NCT02767934
Pembrolizumab in Treating Minimal Residual Disease in Patients With Acute Lymphoblastic Leukemia
A Phase 2 study testing Laboratory Biomarker Analysis and Pembrolizumab in people with B Acute Lymphoblastic Leukemia and Minimal Residual Disease, run by University of Washington at 1 site in United States.
Trial summary
This phase II trial studies how well pembrolizumab works in treating small amounts of cancer cells that remain after attempts to remove the cancer has been made in patients with acute lymphoblastic leukemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B Acute Lymphoblastic Leukemia, Minimal Residual Disease, Recurrent Acute Lymphoblastic Leukemia
- What is being tested?
- Laboratory Biomarker Analysis and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jan 2017to 17 Dec 2019
- 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
- All subjects must have a diagnosis of ALL of either B-cell, T-cell, or mixed (i.e., B/T lineage)
- Be willing and able to provide written informed consent for the trial
- Presence of MRD (defined as < 5% blasts in the bone marrow by morphologic assessment and no clinically-apparent extramedullary disease but with quantifiably-measurable disease as assessed by either MFC or PCR) under any of the following circumstances:
- MRD persistence >= 11 weeks after the start of initial therapy
- MRD persistence >= 2 weeks after the start of salvage therapy, or
- MRD reappearance at any time
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- For patients with Philadelphia chromosome positive (Ph+) disease, have previously received treatment with >= 1 Abelson (ABL) kinase inhibitor (e.g., imatinib, dasatinib, etc.) or are ineligible for such treatment
- Have previously received or are ineligible for treatment with blinatumomab; ineligibility will include (but not be limited to) cluster of differentiation 19 (CD19)-negative disease, denial of insurance coverage, physician discretion, and/or patient refusal
- Be willing to provide tissue from a newly obtained bone marrow aspirate and/or biopsy; newly-obtained is defined as a specimen obtained up to 28 days prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g., inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the principal investigator (PI)
- Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Absolute neutrophil count (ANC) >= 1,000 /mcL (performed within 10 days of treatment initiation)
- Hemoglobin >= 8 g/dL (performed within 10 days of treatment initiation)
- Platelets >= 50,000 /mcL (performed within 10 days of treatment initiation)
- Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance >= 60 mL/min/1.73 m^2 for subject with creatinine levels > 1.5 X institutional ULN (performed within 10 days of treatment initiation) (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl])
- Serum total bilirubin =< 1.5 X ULN 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 ULN (performed within 10 days of treatment initiation)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)
- 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 (performed within 10 days of treatment initiation)
- Female subjects of childbearing potential should have a negative urine or serum pregnancy within 3 days 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
- 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
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational new drug 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 bacillus tuberculosis (TB)
- Has a known 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 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
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- Note: subjects with =< grade 2 neuropathy or with hematologic toxicity that has recovered to levels above that stated in inclusion criterion are an exception to this criterion and may qualify for the study if all other inclusion/exclusion criteria are met
- Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention (i.e., =< grade 1 or at baseline) 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 and/or leukemic meningitis; subjects with previously treated CNS leukemia may participate provided they are stable (e.g., without evidence of active disease by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline) and have no evidence of leukemic blasts on analysis of cerebrospinal fluid (CSF)
- 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
- Has previously received an allogeneic hematopoietic cell transplant, unless the following criteria are met:
- Detection of MRD occurred >= 21 days from stem cell infusion
- No active GVHD
- Receiving systemic steroid therapy of =< 10 mg of prednisone daily (or equivalent)
- Has discontinued systemic immunosuppressant therapy >= 7 days prior to first dose of pembrolizumab
- Has previously received other forms of cellular immunotherapy (e.g., chimeric antigen receptor-modified [CAR] T cells), unless the following criteria are met:
- Detection of MRD occurred >= 21 days from cell infusion
- Any specific manifestations of cytokine release syndrome or neurologic toxicity attributable to the cellular therapy have completely resolved (i.e., < grade 1)
- Has an active infection requiring systemic therapy; antimicrobial prophylaxis will be permitted at the discretion of the treating investigator
- 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 from the time of consent through 120 days after the last dose of trial treatment
- Has received prior therapy with any immune checkpoint inhibitor
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Has known active hepatitis B (e.g., hepatitis B virus surface protein antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [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
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: A Phase II Study of Anti-PD-1 Antibody (MK-3475; Pembrolizumab) for the Treatment of Minimal Residual Disease in Adults With Acute Lymphoblastic Leukemia
This phase II trial studies how well pembrolizumab works in treating small amounts of cancer cells that remain after attempts to remove the cancer has been made in patients with acute lymphoblastic leukemia. 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.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the efficacy of pembrolizumab in minimal residual disease (MRD)-positive acute lymphoblastic leukemia (ALL).
SECONDARY OBJECTIVES:
- To describe the toxicity profile of pembrolizumab in patients with previously-treated ALL.
II. To gain a preliminary assessment of how MRD response translates into relapse-free and overall survival.
EXPLORATORY OBJECTIVES:
- To compare disease assessments by multiparameter flow cytometry (MFC) and polymerase chain reaction (PCR) to a newly-developed and more sensitive next generation sequencing (NGS)-based platform.
II. To correlate response to pembrolizumab to immunologic markers in peripheral blood and bone marrow specimens.
III. To evaluate if treatment with pembrolizumab has a measurable impact on hematopoietic engraftment and graft-vs-host disease (GVHD) in patients who subsequently undergo allogeneic hematopoietic cell transplantation (HCT).
OUTLINE:
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients achieving complete MRD response may receive up to 1 additional year of treatment at the discretion of the investigator.
After completion of study treatment, patients are followed up every 3 months for up to 2 years.
- Conditions
- B Acute Lymphoblastic Leukemia, Minimal Residual Disease, Recurrent Acute Lymphoblastic Leukemia, T Acute Lymphoblastic Leukemia
- Being tested
- Laboratory Biomarker Analysis, Pembrolizumab
- Medical subject headings
- Burkitt Lymphoma, Neoplasm, Residual, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pembrolizumab) | Experimental | Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients achieving complete MRD response may receive up to 1 additional year of treatment at the discretion of the investigator. Receives: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Complete Minimal Residual Disease Response
Will be defined as percentage of evaluable subjects who achieve a complete response. Will be evaluated with a Simon two-stage optimum design.
Measured: Up to 2 years
Secondary outcomes (2)
Overall Survival
Measured: Up to 2 years
Relapse-Free Survival
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2016 (estimated)
- Study start13 Jan 2017
- Primary completion31 Jul 2019
- Study completion17 Dec 2019
Why it stopped: Terminated due to lack of efficacy
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for B Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ryan Cassaday, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02767934
- Sponsor's protocol ID
- 9458
- Other IDs
- NCI-2016-00602, 9458, P30CA015704, RG1016006
- Status last verified
- Jun 2020
- First submitted
- 6 May 2016
- Last updated
- 20 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Cassaday RD, Garcia KA, Fromm JR, Percival MM, Turtle CJ, Nghiem PT, Stevenson PA, Estey EH. Phase 2 study of pembrolizumab for measurable residual disease in adults with acute lymphoblastic leukemia. Blood Adv. 2020 Jul 28;4(14):3239-3245. doi: 10.1182/bloodadvances.2020002403.
PubMed 32692850
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Anti-PD-1 Antibody (MK-3475; Pembrolizumab) for the Treatment of Minimal Residual Disease in Adults With Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT02767934
- Acronym / sponsor ID
- 9458
- Conditions
- B Acute Lymphoblastic Leukemia, Minimal Residual Disease, Recurrent Acute Lymphoblastic Leukemia, T Acute Lymphoblastic Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated due to lack of efficacy
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 13 Jan 2017 (actual)
- Primary completion
- 31 Jul 2019 (actual)
- Study completion
- 17 Dec 2019 (actual)
- First posted
- 11 May 2016 (estimated)
- Results
- Posted 11 Aug 2020
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 how well pembrolizumab works in treating small amounts of cancer cells that remain after attempts to remove the cancer has been made in patients with acute lymphoblastic leukemia. 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.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the efficacy of pembrolizumab in minimal residual disease (MRD)-positive acute lymphoblastic leukemia (ALL).
SECONDARY OBJECTIVES:
- To describe the toxicity profile of pembrolizumab in patients with previously-treated ALL.
II. To gain a preliminary assessment of how MRD response translates into relapse-free and overall survival.
EXPLORATORY OBJECTIVES:
- To compare disease assessments by multiparameter flow cytometry (MFC) and polymerase chain reaction (PCR) to a newly-developed and more sensitive next generation sequencing (NGS)-based platform.
II. To correlate response to pembrolizumab to immunologic markers in peripheral blood and bone marrow specimens.
III. To evaluate if treatment with pembrolizumab has a measurable impact on hematopoietic engraftment and graft-vs-host disease (GVHD) in patients who subsequently undergo allogeneic hematopoietic cell transplantation (HCT).
OUTLINE:
Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients achieving complete MRD response may receive up to 1 additional year of treatment at the discretion of the investigator.
After completion of study treatment, patients are followed up every 3 months for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (pembrolizumab) | Experimental | Other: Laboratory Biomarker Analysis, Biological: PembrolizumabPatients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients achieving complete MRD response may receive up to 1 additional year of treatment at the discretion of the investigator. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- All subjects must have a diagnosis of ALL of either B-cell, T-cell, or mixed (i.e., B/T lineage)
- Be willing and able to provide written informed consent for the trial
- Presence of MRD (defined as < 5% blasts in the bone marrow by morphologic assessment and no clinically-apparent extramedullary disease but with quantifiably-measurable disease as assessed by either MFC or PCR) under any of the following circumstances:
- For patients with Philadelphia chromosome positive (Ph+) disease, have previously received treatment with >= 1 Abelson (ABL) kinase inhibitor (e.g., imatinib, dasatinib, etc.) or are ineligible for such treatment
- Have previously received or are ineligible for treatment with blinatumomab; ineligibility will include (but not be limited to) cluster of differentiation 19 (CD19)-negative disease, denial of insurance coverage, physician discretion, and/or patient refusal
Key exclusion criteria (28 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational new drug 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 bacillus tuberculosis (TB)
- Has a known 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
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 |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (pembrolizumab) |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Biological | Treatment (pembrolizumab) |
Primary outcome
Rate of Complete Minimal Residual Disease Response
Time frame: Up to 2 years
Will be defined as percentage of evaluable subjects who achieve a complete response. Will be evaluated with a Simon two-stage optimum design.
2 secondary outcomes
Overall Survival
Time frame: Up to 2 years
Relapse-Free Survival
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32692850Cassaday RD, Garcia KA, Fromm JR, Percival MM, Turtle CJ, Nghiem PT, Stevenson PA, Estey EH. Phase 2 study of pembrolizumab for measurable residual disease in adults with acute lymphoblastic leukemia. Blood Adv. 2020 Jul 28;4(14):3239-3245. doi: 10.1182/bloodadvances.2020002403.
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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.
Ryan Cassaday principal investigator
Fred Hutch/University of Washington Cancer Consortium
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 Laboratory Biomarker Analysis and Pembrolizumab in people with B Acute Lymphoblastic Leukemia and Minimal Residual Disease, run by University of Washington 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 21 inclusion and 28 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 20 Aug 2020. 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 11 Aug 2020). 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?
Rate of Complete Minimal Residual Disease Response (time frame: Up to 2 years). 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 NCT02767934, 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 20 Aug 2020.