BLAST MRD AML-2: BLockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia 2- A Randomized Phase 2 Study of Anti-PD-1 Pembrolizumab in Combination With Azacitidine and Venetoclax as Frontline Therapy in Unfit Patients With Acute Myeloid Leukemia
Study Details
Study Description
Brief Summary
This phase II trial studies how well azacitidine and venetoclax with or without pembrolizumab work in treating older patients with newly diagnosed acute myeloid leukemia. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. 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 venetoclax with pembrolizumab may increase the rate of deeper/better responses and reduce the chance of the leukemia coming back in patients with newly diagnosed acute myeloid leukemia compared to conventional therapy of azacitidine and venetoclax alone.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVE:
- Assess the percentage of patients with minimal residual disease (MRD) negative complete remission (CR) (MRD-CR) or complete remission with incomplete count recovery (MRD-CRi) with azacitidine (AZA) + venetoclax (VEN) with pembrolizumab during the first 6 cycles and compare to control arm.
SECONDARY OBJECTIVES:
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Assess the investigator-assessed rates of CR/CRi/partial remission (PR)/morphological leukemia free state (MLFS) as defined per the modified International Working Group (IWG) 2003 response criteria with AZA + VEN with pembrolizumab, as well as rates of MRD negative MLFS.
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Rates of complete remission with partial count recovery (CRh) and hematologic improvement (HI) to red blood cells and platelets.
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Assess time to MRD negativity and duration of MRD negative state, event free survival (EFS), relapse free survival (RFS), calculated as the time from initial treatment to either disease relapse or death, duration of response (DOR, defined as the time from first CR/CRi to the date of the first documented relapse or death, whichever occurs first) and overall survival (OS).
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Assess the proportion of patients who develop severe toxicity.
EXPLORATORY OBJECTIVES:
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MRD assessment by duplex sequencing (DS) and comparing DS and multiparameter flow cytometry for MRD detection as an exploratory biomarker.
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Assessment of immune-checkpoint expression and dynamic change of immune cell subsets in response to the combination of checkpoint-inhibition and backbone combination in acute myeloid leukemia (AML).
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High-throughput sequencing of the T-cell receptor (TCR) Vb CDR3 regions on flow cytometrically sorted t-cell subsets to assess the effect of immunotherapy on the diversity of the t-cell repertoire and assess for correlation to clinical outcomes.
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Investigation of protein signatures and ribonucleic acid (RNA) signatures associated with response and efficacy using O-link cytokine panel and RNA-sequencing (seq), respectively.
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Determination of mutational load by whole exome sequencing to assess for correlation with clinical outcomes, immune infiltrating profile, and T cell repertoire diversity and clonality.
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Profiling of deoxyribonucleic acid (DNA) methylation patterns before and after treatment to assess for correlation to response to treatment.
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Correlate gut microbiome at baseline and changes in the microbiome with clinical response, both in standard chemotherapy and immunotherapy/chemotherapy therapy settings.
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MRD assessment using duplex sequencing strategy for circulating cell-free tumor DNA and correlation with long-term outcomes.
IX: Exploring different thresholds of MRD negativity using flow cytometry aside from the 0.1% level that will be used for the primary endpoint purposes (e.g. 0.01%).
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I (AZA + VEN):
INDUCTION THERAPY PHASE: Patients receive azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) on days 1-7 or days 1-5 in week 1 and 1-2 in week 2. Patients also receive venetoclax orally (PO) on days 1-28 of cycle 1 and days 1-21 or 1-28 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY PHASE: Patients receive azacitidine IV over 10-40 minutes or SC on days 1-7 or days 1-5 in week 1 and 1-2 in week 2. Patients also receive venetoclax PO on days 1-28 of cycle 1 and days 1-21 or 1-28 of subsequent cycles. Cycles repeat every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity. After completion of 24 cycles, patients who respond to treatment or have stable disease (SD) may continue treatment per physician discretion.
ARM II (AZA + VEN + PEMBROLIZUMAB):
INDUCTION THERAPY PHASE: Patients receive pembrolizumab IV over 30 minutes on day 8 of cycle 1 and every 3 weeks in cycle 2-6, azacitidine IV over 10-40 minutes or SC on days 1-7 or days 1-5 in week 1 and 1-2 in week 2, and venetoclax PO on days 1-28 of cycle 1 and days 1-21 or 1-28 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY PHASE: Patients receive pembrolizumab IV over 30 minutes on day 8 of cycle 1 and every 3 weeks in cycle 2-6, azacitidine IV over 10-40 minutes or SC on days 1-7 or days 1-5 in week 1 and 1-2 in week 2, and venetoclax PO on days 1-28 of cycle 1 and days 1-21 or 1-28 of subsequent cycles. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. After completion of 24 cycles, patients who respond to treatment or have SD may continue treatment with azacitidine and venetoclax per physician discretion.
After completion of study treatment, patients are followed up every 6 months for up to 3 years
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Arm I (AZA, VEN) INDUCTION THERAPY PHASE: Patients receive azacitidine IV over 10-40 minutes or SC on days 1-7 or days 1-5 in week 1 and 1-2 in week 2. Patients also receive venetoclax PO on days 1-28 of cycle 1 and days 1-21 or 1-28 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY PHASE: Patients receive azacitidine IV over 10-40 minutes or SC on days 1-7 or days 1-5 in week 1 and 1-2 in week 2. Patients also receive venetoclax PO on days 1-28 of cycle 1 and days 1-21 or 1-28 of subsequent cycles. Cycles repeat every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity. After completion of 24 cycles, patients who respond to treatment or have SD may continue treatment per physician discretion. |
Drug: Azacitidine
Given IV or SC
Other Names:
Procedure: Biopsy
Undergo biopsy
Other Names:
Drug: Venetoclax
Given PO
Other Names:
|
| Experimental: Arm II (AZA, VEN, pembrolizumab) INDUCTION THERAPY PHASE: Patients receive pembrolizumab IV over 30 minutes on day 8 of cycle 1 and every 3 weeks in cycle 2-6, azacitidine IV over 10-40 minutes or SC on days 1-7 or days 1-5 in week 1 and 1-2 in week 2, and venetoclax PO on days 1-28 of cycle 1 and days 1-21 or 1-28 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30 minutes on day 8 of cycle 1 and every 3 weeks in cycle 2-6, azacitidine IV over 10-40 minutes or SC on days 1-7 or days 1-5 in week 1 and 1-2 in week 2, and venetoclax PO on days 1-28 of cycle 1 and days 1-21 or 1-28 of subsequent cycles. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. After completion of 24 cycles, patients who respond to treatment or have SD may continue treatment with azacitidine and venetoclax per physician discretion. |
Drug: Azacitidine
Given IV or SC
Other Names:
Procedure: Biopsy
Undergo biopsy
Other Names:
Biological: Pembrolizumab
Given IV
Other Names:
Drug: Venetoclax
Given PO
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of patients with minimal residual disease negative complete remission (MRD-CR) or MRD-complete remission with incomplete count recovery (Cri) with azacitidine (AZA) + venetoclax (VEN) with MK-3475 (pembrolizumab) [Up to 6 cycles (each cycle is 28 days)]
Secondary Outcome Measures
- Proportion of patients who develop severe toxicity [Up to cycle 2 (each cycle is 28 days)]
Other Outcome Measures
- Biomarkers or serial measurements of biomarkers associated with response outcomes [Baseline up to 3 years]
A univariate logistic regression will be selected to assess baseline biomarkers associated with response outcomes. The dynamic changes of PD-L1/ PD-1 expressions, concentration of cytokine, and ribonucleic acid (RNA) sequencing (seq)/T-cell receptor (TCR) seq etc. will be monitored. The measurements of biomarkers in changes over time from baseline to several time-points will be performed by using generalized linear mixed effects modeling with a Benjamini-Hochberg correction to control for false discovery rates.
- Biomarkers or serial measurements of biomarkers associated with survival outcomes [Baseline up to 3 years]
The Kaplan-Meier method and log-rank test will be used to estimate the distribution of survival between/among different marker strata. Univariate or Multivariate cox proportional hazard models will be employed to explore the significance of biomarkers on survival outcomes, while adjusting for the potential prognostic factors. The interaction effects between treatment and biomarkers also will be evaluated. Serial measurements of biomarkers will be estimated at baseline, end of induction, post-cycle 1, 2, 4, and 6, every 3 months during maintenance, one year, and end of treatment when applicable. Landmark analysis or joint modeling will be used to assess serial measurements of biomarkers dynamical impacts on survival outcomes, where appropriate.
- Biomarkers effects between treatment arms [Up to 3 years]
The associations between treatment arms and baseline biomarkers will be evaluated using Chi-squared test/ Fisher's exact test, analysis of variance (ANOVA) and the Mann-Whitney U tests as appropriate. Trajectory trends of the changes in markers' values or status across the measurement time will be explored using generalized linear mixed models. The bar plots and trajectory time plots will visually show the differences over time between treatment arms. The associations between markers and the demographic/prognostic factors will also be assessed using the similar statistical methods.
- Correlations between biomarkers [Up to 3 years]
The correlations between biomarkers will be evaluated using Pearson/Spearman rank-order correlation coefficients, Chi-squared/Fisher's exact tests, and Wilcoxon rank sun / Kruskal-Wallis tests as appropriate. A scatter plot, boxplot, and mosaic plot will also be generated for visualization. The multiplicity of the endpoints will be adjusted using the correction of Benjamini and Hochberg.
- MRD assessment [Up to 3 years]
Library preparation, sequencing, and analysis will be performed with TwinStrand's optimized workflow, and TwinStrand's bioinformatics core will perform all analyses related to assay output.
- Cytokine panel analysis [At day 30 (after administration of pembrolizumab and count recovery) and after cycles 2, 4, and 6 (each cycle is 28 days)]
IFN-gamma+/CD3+/ CD4+ or IFN-gamma+/CD3+/CD8+ events will be gated and percentages of the total CD4+ and CD8+ T cells will be determined. Will compare levels of leukemia specific T-cell.
- Expression of PD-1, PD-L1 in acute myeloid leukemia (AML) bone marrow (BM) [At day 14 and at time of count recovery]
An association of clinical response with the expression of PD-L1 AML BM cells will be assessed by a Pearson chi-square test on a 2x2 table of frequencies.
- Dynamic change of immune subsets [Baseline up to cycle 6 (each cycle is 28 days)]
Statistical analyses of the frequency of CD8+, CD4+, Foxp3 regulatory T cells (Tregs), CD8+/Foxp3+ Tregs, central memory T cell (TCM)/effector memory T cell re-expressed CD45RA (TEMRA), effector memory T cell (TEM)/TEMRA, the percentage of Ki67 and GzmB in PD-1+, Eomes+ CD8 T cells to compare changes over time from baseline to several time-points will be performed by using mixed effects modeling with a Benjamini-Hochberg correction to control for false discovery rates.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Newly diagnosed and pathologically-confirmed, previously untreated AML as defined by World Health Organization (WHO) criteria. Bone marrow biopsy, or aspirate or peripheral blood that were obtained up to 3 weeks before signing consent are allowed for purposes of confirming AML diagnosis for eligibility purposes. Secondary AML arising from prior myelodysplastic syndrome (MDS), as long as they have not received more than full cycle of hypomethylating agent therapy for MDS, and therapy related (t)-AML are also allowed. AML arising from prior antecedent hematologic disorders defined as MDS, mycoplasma pneumoniae (MPN), or aplastic anemia are allowed. Note 1: Patients must have evidence of bone marrow involvement on aspirate or biopsy. Patients with only extramedullary disease and no bone marrow involvement will be excluded. Note 2: Every effort should be made to get an aspirate for central flow assessment at screening and all subsequent required time points, but in cases where an aspirate cannot be collected-including dry taps-the patient will not be excluded and assessments will be performed on peripheral blood (PB) which should be collected at every time that bone marrow (BM) is collected. Note 3: Some patients with AML require initiation of therapy quickly after diagnosis, and full metaphase karyotype results in some centers can take 2-3 weeks to result. To avoid this issue being an impediment to accrual to study or to cause delays in initiation of therapy in patients who need fast initiation of therapy, we allow use of karyotype and/or fluorescence in situ hybridization (FISH) results on samples from blood or marrow that were obtained up to 3 weeks before signing consent for purposes of eligibility and stratification. In any case, results from FISH or karyotype should exclude presence of core-binding factor (CBF) abnormalities by time of randomization
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Age >= 60 years
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Patients who are ineligible for intensive chemotherapy according to treating physician's assessment or who refuse intensive chemotherapy
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Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
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Prior use of lenalidomide, erythropoiesis-stimulating agents (ESAs), and growth factors is allowed if used to treat prior MDS. AML must be previously untreated except for hydroxyurea, or all-trans retinoic acid (ATRA) for suspicion of APL but both should be discontinued prior to initiation of study therapy. Hypomethylating agents are not allowed to have been used for AML therapy. If hypomethylating agent therapy was used for prior MDS or MPN therapy then it should not have exceeded one full cycle. Note: One dose of prophylactic intrathecal therapy is allowed during or before screening if a lumbar puncture is performed to rule out central nervous system (CNS) involvement
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Hydroxyurea or leukopheresis are allowed for management of hyperleukocytosis, as well as ATRA, before initiation of study therapy. White blood cell (WBC) count must be < 25 x 10^9/L to start on study therapy per venetoclax label. Hydroxyurea and ATRA may be administered up to one day prior to start of study treatment
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Intermediate-risk or poor risk AML as well as favorable risk by National Comprehensive Cancer Network (NCCN)/European LeukemiaNet (ELN) with the exception of "good-risk" cytogenic profile (i.e., for eligibility patient should lack the presence of t(8;21), (inv[16] or t[16;16]), or t(15;17) by full cytogenetics or FISH). Clarification: We allow use of karyotype and/or FISH results (as well as FLT3 results) on samples from blood or marrow that were obtained up to 3 weeks before signing consent for purposes of eligibility and stratification. Adverse karyotype can be determined based on FISH results (e.g., loss of chromosome 7 or 5 or 3 or more abnormalities) based on the specific probes used in the FISH. If results of full metaphase karyotype are not available and the available FISH results do not suggest an adverse karyotype, and there is a need to initiate therapy before those full results are available, then the patient can be stratified into the unknown/intermediate NCCN cytogenetic group for randomization purposes. In any case, results from FISH or karyotype should show that CBF abnormalities are NOT present by at time of randomization as the presence of CBF abnormalities is an exclusion factor
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Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN
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Creatinine clearance (CrCl) should be calculated per institutional standard
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Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl
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Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN
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Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN OR =< 5 x ULN for patients with liver metastases
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Patients who are human immunodeficiency virus (HIV) positive may participate IF they meet the following eligibility requirements:
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They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective
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Patients must have an undetectable HIV viral load
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Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
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Patients who have undergone major surgery must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
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Female patients of childbearing potential must have a negative urine or serum pregnancy test 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. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or
- has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). Female patients of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. Male patients who have a female partner 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 patient
- Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
Exclusion Criteria:
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Patients with core binding factor (CBF)-AML and acute promyelocytic leukemia (APL)
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Received a prior anti-cancer monoclonal antibodies (mAb) within 4 weeks prior to study registration or have not recovered (recovery defined as baseline or =< grade 1) from adverse events (AEs) due to agents administered more than 4 weeks earlier
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Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
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Patients who have had chemotherapy, targeted small molecule therapy (aside from imatinib, dasatinib, or nilotinib, hydroxyurea, or ATRA), or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
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Left ventricular ejection fraction < 50% as determined by either echocardiogram or multi-gated acquisition (MUGA)
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Patients who have not recovered from AEs due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of =< grade 2 neuropathy and alopecia
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NOTE: Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=< 2 weeks of radiotherapy) to non-central nervous system (CNS) disease
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Patients currently participating and receiving study therapy or have 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 are ineligible
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History of hypersensitivity to pembrolizumab (MK-3475) or any of its excipients, or other agents used in this study
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Current use of systemic corticosteroids or immunosuppressive agents
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EXCEPTION: Low doses of steroids (e.g., < 10 mg of prednisone or equivalent dose of other steroid), used for treatment of non-hematologic medical condition (e.g., chronic adrenal insufficiency) inhaled corticosteroids, or topical steroids are permitted
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Other active primary malignancy (other than non-melanomatous skin cancer or carcinoma in situ of the cervix) requiring treatment or limiting expected survival to =< 2 years
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NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy for their cancer)
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Patient with known active CNS disease and/or carcinomatous meningitis before study enrollment. Assessment of the cerebrospinal fluid (CSF) is not required to enroll in the study unless there is clinical suspicion for CNS involvement. However, if CSF assessment is performed for any reason, there should be no evidence of active leukemia in the CSF as per investigator judgement. Up to one dose of prophylactic intrathecal chemotherapy is allowed prior to study enrollment. 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 protocol 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 protocol treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
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Patients who received prior allogenic transplant
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Patient with 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
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Patient with a diagnosis of immunodeficiency or receiving high dose systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment
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Patient with active autoimmune disease except for patients with hypothyroidism and vitiligo 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
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Patient with a known history of non-infectious pneumonitis that required the use of steroids or current non-infectious pneumonitis
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Patient with active uncontrolled infection
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Patient with a known history of active TB (Bacillus tuberculosis)
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Patients with uncontrolled intercurrent illness
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Patients with psychiatric illness/social situations that would limit compliance with study requirements
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Pregnant women are excluded from this study because pembrolizumab (MK-3475) is humanized antibody with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab, breastfeeding should be discontinued if the mother is treated with pembrolizumab. These potential risks may also apply to other agents used in this study
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Patients with no bone marrow involvement (i.e., those with only extramedullary disease)
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Patients who received prior hypomethylating agent (HMA) therapy for more than one full cycle in treatment for prior MDS. Patient must not have received HMA therapy for treatment of AML
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Patients that received a live vaccine within 30 days of planned start of study therapy
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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
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Patients with active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment. Patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Yale University | New Haven | Connecticut | United States | 06520 |
| 2 | MedStar Georgetown University Hospital | Washington | District of Columbia | United States | 20007 |
| 3 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 4 | HaysMed University of Kansas Health System | Hays | Kansas | United States | 67601 |
| 5 | University of Kansas Cancer Center | Kansas City | Kansas | United States | 66160 |
| 6 | Lawrence Memorial Hospital | Lawrence | Kansas | United States | 66044 |
| 7 | Olathe Health Cancer Center | Olathe | Kansas | United States | 66061 |
| 8 | University of Kansas Cancer Center-Overland Park | Overland Park | Kansas | United States | 66210 |
| 9 | Ascension Via Christi - Pittsburg | Pittsburg | Kansas | United States | 66762 |
| 10 | Salina Regional Health Center | Salina | Kansas | United States | 67401 |
| 11 | University of Kansas Health System Saint Francis Campus | Topeka | Kansas | United States | 66606 |
| 12 | University of Kansas Hospital-Westwood Cancer Center | Westwood | Kansas | United States | 66205 |
| 13 | Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | United States | 21287 |
| 14 | Siteman Cancer Center at West County Hospital | Creve Coeur | Missouri | United States | 63141 |
| 15 | Truman Medical Centers | Kansas City | Missouri | United States | 64108 |
| 16 | University of Kansas Cancer Center - North | Kansas City | Missouri | United States | 64154 |
| 17 | University of Kansas Cancer Center - Lee's Summit | Lee's Summit | Missouri | United States | 64064 |
| 18 | University of Kansas Cancer Center at North Kansas City Hospital | North Kansas City | Missouri | United States | 64116 |
| 19 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 20 | Siteman Cancer Center-South County | Saint Louis | Missouri | United States | 63129 |
| 21 | Siteman Cancer Center at Christian Hospital | Saint Louis | Missouri | United States | 63136 |
| 22 | Siteman Cancer Center at Saint Peters Hospital | Saint Peters | Missouri | United States | 63376 |
| 23 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 24 | Wake Forest University at Clemmons | Clemmons | North Carolina | United States | 27012 |
| 25 | Wake Forest Baptist Health - Wilkes Medical Center | Wilkesboro | North Carolina | United States | 28659 |
| 26 | Wake Forest University Health Sciences | Winston-Salem | North Carolina | United States | 27157 |
| 27 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Amer M Zeidan, Yale University Cancer Center LAO
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2020-01016
- NCI-2020-01016
- 10334
- 10334
- UM1CA186689