Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Amino Acids

Etoposide

Cytarabine

Venetoclax

Mitoxantrone

Fludarabine

Fludarabine phosphate

Azacitidine

Daunorubicin

Etoposide phosphate

Gilteritinib

Idarubicin

Gemtuzumab

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Enzyme Inhibitors

Antiviral Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

All eligible patients receive intervention according to the Detailed Description section with the following:

Venetoclax, Cytabrine, Danunorubicin Hydrochloride, Gemtuzumab Ozogamicin, Etoposide, Mitoxantrone Hydrochloride, Gilteritinib

All eligible patients receive intervention according to the Detailed Description section with the following:

Venetoclax, Cytabrine, Danunorubicin Hydrochloride, Fludarabine Phosphate, Gemtuzumab Ozogamicin, Etoposide, Idarubin Hydrochloride, Mitoxantrone Hydrochloride, Gilteritinib

All eligible patients receive intervention according to the Detailed Description section with the following:

Venetoclax, Azacitidine, Cytabrine, Danunorubicin Hydrochloride, Fludarabine Phosphate, Gemtuzumab Ozogamicin, Etoposide, Idarubin Hydrochloride, Gilteritinib

Venetoclax will be given with each course of therapy. Patients with low-risk AML will receive four courses of therapy, intermediate-risk patients will receive five courses of therapy, and high-risk patients will receive two or three courses of therapy followed by hematopoietic stem cell transplantation.

Given IV over 30 minutes q12 hours on days 1-8 (16 doses)

Gemtuzumab Ozogamicin

Daunorubicin Hydrochloride

Fludarabine Phosphate

Idarubicin Hydrochloride

Mitoxantrone Hydrochloride

Jeffrey E. Rubnitz, MD, PhD

This is a phase 2 study to test the hypothesis that venetoclax in combination with standard chemotherapy will be tolerable and active in pediatric patients with newly diagnosed acute myeloid leukemia (AML).

Primary Objectives:

* Establish the tolerability adding venetoclax to standard chemotherapy in pediatric patients with AML
* Estimate the proportion of patients who become minimal residual disease (MRD) negative by flow cytometry after one course of venetoclax-based induction therapy

Secondary Objectives:

- Estimate the rates of complete remission (CR), event-free survival (EFS), and overall survival (OS) in pediatric patients who receive venetoclax-based chemotherapy

Treatment will be based on genetic characteristics and response to therapy. Venetoclax will be given with each course of therapy. Low-risk patients will receive four courses of chemotherapy and intermediate-risk patients will receive five courses. High-risk patients who do not have a suitable stem cell donor or who decline HCT will receive five courses of chemotherapy. The definition of suitable stem cell donor and the conditioning regimens used for HCT will be determined by local institutional protocols or guidelines.

Intervention:

Low Risk

Induction 1: Venetoclax orally (PO) once daily (QD) on days -2 to 11, cytarabine intravenously (IV) over 30 minutes every 12 hours on days 1-8, daunorubicin hydrochloride IV over 1 hour QD on days 1, 3, and 5, etoposide IV over one hour QD on days 1-5, and gemtuzumab ozogamicin IV over 2 hours on day 6.

Induction 2: Venetoclax PO QD on days 1-14, cytarabine IV over 30 minutes every 12 hours on days 1-8, daunorubicin hydrochloride IV over 1 hour QD on days 1, 3, and 5, and etoposide IV over 1 hour QD on days 1-5.

Intensification: Venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-4, and mitoxantrone hydrochloride IV over 1 hour QD on days 2-4 during intensification 1 and then venetoclax PO QD on days 1-7 and high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5 during intensification 2. Patients with FLT3 activation receive sorafenib PO QD on days 8-28 during intensification 1 and 2.

Intermediate Risk

Induction 1: Venetoclax orally (PO) once daily (QD) on days -2 to 11, cytarabine intravenously (IV) over 30 minutes every 12 hours on days 1-8, daunorubicin hydrochloride IV over 1 hour QD on days 1, 3, and 5, etoposide IV over one hour QD on days 1-5, and gemtuzumab ozogamicin IV over 2 hours on day 6.

Induction 2: Venetoclax PO QD on days 1-14, fludarabine phosphate IV over 30 minutes QD on days 1-5, cytarabine IV over 3 hours QD starting 4 hours after each dose of fludarabine on days 1-5, idarubicin hydrochloride IV over 15 minutes QD on days 3-5. Patients with FLT3 activation receive sorafenib PO QD on days 8-28.

Intensification: Venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-4, and mitoxantrone hydrochloride IV over 1 hour QD on days 2-4 during intensification 1, venetoclax PO QD on days 1-7 and high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5 during intensification 2, and then venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-5, and etoposide IV over 1 hour QD on days 1-5 during intensification 3. Patients with FLT3 activation receive sorafenib PO QD on days 8-28 during intensification 1-3.

High Risk

Induction 1: Venetoclax orally (PO) once daily (QD) on days -2 to 11, cytarabine intravenously (IV) over 30 minutes every 12 hours on days 1-8, daunorubicin hydrochloride IV over 1 hour QD on days 1, 3, and 5, etoposide IV over one hour QD on days 1-5, and gemtuzumab ozogamicin IV over 2 hours on day 6.

Induction 2: Venetoclax PO QD on days 1-14, fludarabine phosphate IV over 30 minutes QD on days 1-5, cytarabine IV over 3 hours QD starting 4 hours after each dose of fludarabine on days 1-5, idarubicin hydrochloride IV over 15 minutes QD on days 3-5. Patients with FLT3 activation receive sorafenib PO QD on days 8-28.

Intensification: Patients with MRD \< 0.1% proceed directly to HCT if donor is available. If a donor is not yet available, patients with MRD \< 0.1% may receive ventoclax PO QD on days 1-21 and azacitidine IV over 30 minutes QD on days 1-5 or venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-5, and etoposide IV over 1 hour QD on days 1-5. Patients with MRD 0.1% to \< 1% may receive ventoclax PO QD on days 1-21 and azacitidine IV over 30 minutes QD on days 1-5 or venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-5, and etoposide IV over 1 hour QD on days 1-5. Patients with MRD \>= 1% may receive venetoclax PO QD on days 1-10, azacitidine IV over 30 minutes QD on days 1-5, and high-dose cytarabine IV over 3 hours every 12 hours on days 6, 8, and 10. Patients with FLT3 activation receive sorafenib PO QD on days 8-28.

A Study of Venetoclax in Combination With Conventional Chemotherapy in Pediatric Patients With Acute Myeloid Leukemia

A Collaboration Phase 2 Study of Venetoclax in Combination With Conventional Chemotherapy in Pediatric Patients With Acute Myeloid Leukemia

Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

Will compute a binomial confidence interval for the proportion of MRD-evaluable patients who become MRD-negative (defined as MRD \< 0.1%) after induction 1.

A patient is deemed to have tolerated a course of therapy if they complete that course without death or an unacceptable adverse event. Will monitor the tolerability or each course using multi-stage binomial stopping rules. Will use the method of Jung and Kim to compute 95% confidence intervals that adjust for the multi-stage monitoring.

The Kaplan-Meier method will be used and 95% confidence intervals will be computed for event-free survival at 3 years.

The Kaplan-Meier method will be used and 95% confidence intervals will be computed for overall survival at 3 years.

AbbVie

St. Jude Children's Research Hospital

Symptoms and General Pathology

Neoplasm Metastasis

Syndrome

Preleukemia

Myelodysplastic Syndromes

Neoplasm, Residual

Bone Marrow Diseases

Neoplastic Processes

Antibodies

Pembrolizumab

Immunoglobulins

Immune Checkpoint Inhibitors

Biospecimen Collection

Bone Marrow Aspiration

Bone Marrow Biopsy

Computed Tomography

Echocardiography

Hematopoietic Cell Transplantation

Multigated Acquisition Scan

Punch Biopsy

Amer Zeidan

Site Public Contact

Pankit Vachhani

Deepa Jeyakumar

Rory M. Shallis

Talha Badar

Shira N. Dinner

Swaroopa Yerrabothala

Keri R. Maher

Amer M Zeidan

This phase II trial studies how well cytarabine and idarubicin or daunorubicin with or without pembrolizumab work in treating patients with newly-diagnosed acute myeloid leukemia. Chemotherapy drugs, such as cytarabine, idarubicin, and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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 induction chemotherapy with pembrolizumab may work better than induction chemotherapy alone in treating patients with acute myeloid leukemia.

PRIMARY OBJECTIVE:

I. To assess the percentage of patients with minimal residual disease (MRD) negative complete remission (CR) (MRD-CR) as measured by flow cytometry at the end of first cycle of consolidation therapy with chemotherapy + pembrolizumab (MK-3475) and compare between the two study arms.

SECONDARY OBJECTIVES:

I. Assess the rate of complete remission (CR)/complete remission with incomplete count recovery (CRi) as defined per European LeukemiaNet 2017 response criteria at time of count recovery after induction therapy with chemotherapy + pembrolizumab (MK-3475) (Dohner et al., 2017).

II. Rates of complete remission with partial recovery count (CRh) and hematologic improvement (HI) to red blood cells and platelets.

III. Assess the rates of MRD negativity at day 14, MRD-negative CR at end of induction therapy and MRD negative CR after last consolidation cycle.

IV. Assess event free survival (EFS), measured from randomization to failure to achieve CR/CRi, relapse or death from any cause, and relapse free survival (RFS), calculated as the time from first documentation of CR/CRi to either disease relapse or death from any cause.

V. Assess the 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), defined as time from randomization to death from any cause.

VI. Assess safety endpoints including proportion of patients who develop severe toxicity as defined in the protocol.

EXPLORATORY OBJECTIVES:

I. MRD assessment by duplex sequencing (DS) and comparing DS and multiparameter flow cytometry for MRD detection as an exploratory biomarker.

II. 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).

III. 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.

IV. Investigation of protein signatures and ribonucleic acid (RNA) signatures associated with response and efficacy using O-link cytokine panel and RNA-sequencing (seq), respectively.

V. 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.

VI. Correlate gut microbiome at baseline and changes in the microbiome with clinical response, both in standard chemotherapy and immunotherapy/chemotherapy therapy settings.

VII. MRD assessment using duplex sequencing strategy for circulating cell-free tumor deoxyribonucleic acid (DNA) and correlation with long-term outcomes.

OUTLINE: Patients are randomized to 1 of 2 arms.

INDUCTION PHASE:

ARM I: Patients receive cytarabine via continuous intravenous (IV) infusion on days 1-7 and idarubicin hydrochloride IV over 15-30 minutes or daunorubicin hydrochloride IV over 15-30 minutes on days 1-3 of a 28-35 day cycle. Patients who have evidence of residual leukemia receive cytarabine via continuous IV infusion over days 1-5 and idarubicin hydrochloride IV over 15-30 minutes or daunorubicin hydrochloride IV over 15-30 minutes on days 1-2 for an additional cycle in the absence of disease progression or unacceptable toxicity. Beginning day 8, patients receive pembrolizumab IV over 25-40 minutes. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve a CR or a CRi may undergo hematopoietic stem cell transplantation (HSCT) per physician discretion or continue to consolidation therapy.

ARM II: Patients receive cytarabine via continuous IV infusion on days 1-7 and idarubicin hydrochloride IV over 15-30 minutes or daunorubicin hydrochloride IV over 15-30 minutes on days 1-3 of a 28-35 day cycle. Patients who have evidence of residual leukemia receive cytarabine via continuous IV infusion over days 1-5 and idarubicin hydrochloride IV over 15-30 minutes or daunorubicin hydrochloride IV over 15-30 minutes on days 1-2 for an additional cycle in the absence of disease progression or unacceptable toxicity. Patients who achieve a CR or a CRi may undergo HSCT per physician discretion or continue to consolidation therapy.

CONSOLIDATION THERAPY:

ARM I: Within 4 weeks of remission status documentation, patients receive high-dose cytarabine (HiDAC) IV over 1-3 hours every 10-12 hours on days 1, 3, and 5 for a total of 6 doses and pembrolizumab IV over 25-40 minutes. Cycles with HiDAC repeat every 28-42 days and cycles with pembrolizumab repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients who remain in CR or CRi receive up to 3 additional cycles of HiDAC and pembrolizumab in the absence of disease progression or unacceptable toxicity and continue to maintenance therapy.

ARM II: Within 4 weeks of remission status documentation, patients receive HiDAC IV over 1-3 hours every 12 hours on days 1, 3, and 5 for a total of 6 doses in the absence of disease progression or unacceptable toxicity. Patients who remain in CR or CRi receive up to 3 additional cycles of HiDAC in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY:

ARM I: Patients receive pembrolizumab IV over 25-40 minutes. Cycles repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

All patients also undergo a skin punch biopsy during screening and undergo bone marrow biopsy and aspiration, collection of blood samples, and echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening and on study. Patients may optionally undergo computed tomography (CT) scan during screening.

After completion of study treatment, patients are followed up at 30 days and then every 6 months for up to 5 years. Patients who undergo HSCT are also followed up at 100 days post-transplant.

BLAST MRD AML-1: BLockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia 1- A Randomized Phase 2 Study of Anti-PD-1 Pembrolizumab in Combination With Intensive Chemotherapy as Frontline Therapy in Patients With Acute Myeloid Leukemia

BLockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia 1 (BLAST MRD AML-1): A Randomized Phase 2 Study of the Anti-PD-1 Antibody Pembrolizumab in Combination With Conventional Intensive Chemotherapy as Frontline Therapy in Patients With Acute Myeloid Leukemia

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Will be assessed by duplex sequencing. 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.

Will compare duplex sequencing and multiparameter flow cytometry for MRD detection. McNemar's Chi-squared test for paired samples (regular duplex sequencing versus multiparameter flow cytometry and ultra-deep duplex sequencing versus multiparameter flow cytometry) will be used to compare the MRD measures.

Will assess immune cell subsets and correlate with response to combine chemotherapy and anti PD-1 directed therapy using mass cytometry. All data will be analyzed and graphs generated using the DVS Cytobank software (Cytobank). Will also measure CD47 levels on leukemic blasts prior to and after chemotherapy and pembrolizumab application to see whether CD47 expression levels correlate with responders versus non-responders and whether expression levels change at different times of therapy. Statistical analyses of the frequency of CD8 positive (+), CD4+, Foxp3 T regulatory cells (Tregs), CD8+/Foxp3+ Tregs, central memory effector (TCM)/ memory cells that re-express CD45RA (TEMRA), effector memory (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.

An association of clinical response with the expression of PD-L1 acute myeloid leukemia bone marrow cells will be assessed by a Pearson Chi-square test on a 2 x 2 table of frequencies. The dependent variable will be defined as response (yes versus no), and quantitative immunofluorescence categories (negative versus positive) will be the independent variables. Will also monitor the dynamic change of PD-L1 expression over the course of treatment and its correlation with clinical response. Longitudinal measurements of PD-L1 will be examined using mixed-effects modeling.

Will use massively parallel sequencing technology to sequence the genomic DNA of tumor cells (leukemic bone marrow) and normal cells (germline) obtained from patients with acute myeloid leukemia. Mutational load by whole-exome sequencing will be correlated with clinic-pathological parameters such as response to treatment, survival and immune infiltrating profile, and T cell repertoire diversity and clonality.

Will investigate protein signatures associated with response and efficacy using the Olink inflammation biomarker panel.

Will be assessed using either the Agilent 4200 TapeStation and High Sensitivity RNA ScreenTape or the Agilent 2100 Bioanalyzer and RNA 6000 Pico Chip. Either method will employ the region analysis method to determine the percentage of RNA in the sample that is \> 200 nt for each sample to be processed.

Will perform high-throughput sequencing of the TCR V beta 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. TCR diversity and clonality will be calculated using a software by Adaptive Technologies. T-cell repertoire diversity and clonality will be correlated with clinic-pathological parameters such as response to treatment, survival, and immune infiltrating profile, as well as genomic profiles (total mutation burden, non-synonymous mutation burden, predicted neoantigen burden, clonal mutation burden and clonal predicted neoantigen burden). TCR profile generated from treatment-refractory tumors at the time of disease progression will be compared to data from pre-treatment tumor samples to explore the TCR repertoire evolution of these tumors under therapeutic pressure.

Analysis of microbiome communities will be performed in R. Pairwise differences in temporal variability across body sites will be made using Mann-Whitney U test, whereas pairwise differences among response groups performed using Student's t-test. Correlation between microbial/metabolome changes with immune-checkpoint expression and kinetics of immune cell subset recovery and programming in the standard of care and experimental arm will be evaluated. As a marker of mucosal immunity, changes in immune cell content within stool samples in patients that experience colitis or gastrointestinal graft versus host disease will be compared to suitable controls.

MRD will be assessed by multicolor flow cytometry as an integral biomarker.

Will be defined per European LeukemiaNet 2017.

Median RFS will be estimated with Kaplan-Meier curves with 95% confidence interval calculated based on the Brookmeyer-Crowley method

Median DOR will be estimated with Kaplan-Meier curves with 95% confidence interval calculated based on the Brookmeyer-Crowley method.

Will be assessed per Common Terminology Criteria for Adverse Events version 5.0.

National Cancer Institute (NCI)

Myeloproliferative Disorders

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Precancerous Conditions

Myelodysplastic-Myeloproliferative Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Myelodysplastic/myeloproliferative Disease

Dermatologic Agents

Pomalidomide

Podophyllotoxin

Angiogenesis Inhibitors

Growth Inhibitors

Keratolytic Agents

Tubulin Modulators

Antimitotic Agents

Laboratory Biomarker Analysis

Pharmacological Study

Ivana Gojo

This phase I trial studies the side effects and best dose of pomalidomide after combination chemotherapy in treating patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Drugs used in chemotherapy, such as cytarabine, daunorubicin hydrochloride, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Pomalidomide may kill cancer cells by stopping blood flow to the cancer and by stimulating white blood cells to kill cancer cells. Giving more than one drug (combination chemotherapy) and pomalidomide may kill more cancer cells.

PRIMARY OBJECTIVES:

I. To define the maximum tolerated dose (MTD) of pomalidomide when given at the time of early lymphocyte recovery following intensive induction timed sequential therapy (TST) with cytarabine (cytosine arabinoside), daunorubicin hydrochloride (daunorubicin) and etoposide (AcDVP-16) in patients with newly diagnosed intermediate- and poor-risk acute myeloid leukemia and high-risk myelodysplastic syndrome (MDS).

II. To evaluate the safety, tolerability and toxicity of pomalidomide given at the time of early lymphocyte recovery following induction AcDVP-16 chemotherapy in adults with newly diagnosed intermediate- and poor-risk acute myeloid leukemia and high-risk MDS.

SECONDARY OBJECTIVES:

I. To evaluate the safety, tolerability and toxicity of pomalidomide given as a continuation therapy following induction and/or consolidation chemotherapy in adults with newly diagnosed intermediate- and poor-risk acute myeloid leukemia and high-risk MDS.

II. To document responses (complete remission \[CR\], CR with incomplete count recovery \[CRi\], partial remission \[PR\]) to AcDVP-16 followed by pomalidomide at the time of lymphocyte recovery in newly diagnosed adults with intermediate- and poor-risk acute myeloid leukemia (AML) and high-risk MDS, including duration of response, disease-free and overall survival.

III. Correlative pharmacodynamics studies: a) to characterize the effects of pomalidomide on the functional dynamics of different lymphocyte subpopulations (effector T \[Teff\], regulatory T \[Treg\], natural killer \[NK\] cells) and its impact on tumor-associated antigen (TAA)-specific T cell immunity when given following induction and as a maintenance; b) to examine for the presence of minimal residual disease (MRD) before and after pomalidomide administration during induction and continuation therapy; c) to examine cereblon expression in primary leukemia cells at diagnosis and in sorted T cells prior to and after pomalidomide treatment.

OUTLINE: This is a dose-escalation study of pomalidomide.

INDUCTION: Patients receive cytarabine intravenously (IV) continuously and daunorubicin hydrochloride IV on days 1-3 (patients may otherwise receive idarubicin hydrochloride IV over 10-15 minutes on days 1-3 if daunorubicin hydrochloride is unavailable), and etoposide IV over 3 hours on days 8-10. At the time of early lymphocyte recovery (after day +14), patients also receive pomalidomide orally (PO) for 10-21 days.

CONSOLIDATION: Patients achieving CR or CRi receive cytarabine based treatment at the discretion of the treating investigator, with possible regimens comprising cytarabine IV continuously on days 1-3, and 10-12 and daunorubicin hydrochloride IV on days 1-3, or high- or medium-dose cytarabine IV every 12 hours on days 1, 3, and 5 for 1-4 courses.

CONTINUATION: Patients achieving CR or CRi who did not undergo allogeneic stem cell transplant receive pomalidomide PO daily on days 1-21 beginning 6 weeks following blood count recovery. Treatment repeats every 4-6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years.

Pomalidomide After Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

A Phase I Study of Pomalidomide Given at the Time of Lymphocyte Recovery Following Induction Timed Sequential Chemotherapy With Cytarabine, Daunorubicin and Etoposide (AcDVP16) in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) and High-Risk MDS

Boxplots and line plots will be used to visual trends in the lymphocyte subpopulations. Changes and percentage changes in variables will be summarized. 95% confidence intervals will be obtained by exponentiating the endpoints of confidence intervals for the differences of mean logarithms. A regression model using generalized estimating equations or mixed model used to assess T cell changes. Association of bone marrow and peripheral blood measurements assessed using scatterplots and Spearman's rank correlation coefficients.

McNemar's test will be used to compare proportions with positive tumor specificity before and after pomalidomide treatment. Sensitivity and specificity of induction responses for predicting complete remission status will be estimated.

Presence or absence of minimal residual disease on day 14 will be correlated with minimal residual disease following induction pomalidomide. McNemar's test will be used to compare proportions. Presence or absence of residual leukemic stem cells immediately following induction will be correlated with progression-free survival using the Kaplan-Meier survival method.

Will examine in relation to clinical parameters as well as T cell reconstitution.

The proportion of dose-limiting toxicities at each dose level will be reported with exact binomial 95% confidence intervals. Adverse events will be summarized by dose level for all doses. All toxicities by type and grade will be reported.

The proportion of toxicities by type and grade in the expansion cohort will be reported with exact binomial 95% confidence intervals.

The proportion of patients achieving each category of response will be reported with 95% exact binomial confidence intervals.

Standard life table methods will be used to analyze progression-free survival. One-year and median progression-free survival with 95% confidence intervals will be reported.

Standard life table methods will be used to analyze overall survival.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Venetoclax in Combination With Conventional Chemotherapy in Pediatric Patients With Acute Myeloid Leukemia	NCT05955261	Acute Myeloid L...	Venetoclax Azacitidine Cytarabine Gemtuzumab Ozog... Daunorubicin Hy... Fludarabine Pho... Idarubicin Hydr... Mitoxantrone Hy... Etoposide Gilteritinib	29 Days - 21 Years	St. Jude Children's Research Hospital
BLAST MRD AML-1: BLockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia 1- A Randomized Phase 2 Study of Anti-PD-1 Pembrolizumab in Combination With Intensive Chemotherapy as Frontline Therapy in Patients With Acute Myeloid Leukemia	NCT04214249	Acute Myeloid L... Acute Myeloid L... Acute Myeloid L... Secondary Acute...	Biospecimen Col... Bone Marrow Asp... Bone Marrow Bio... Computed Tomogr... Cytarabine Daunorubicin Hy... Echocardiograph... Hematopoietic C... Idarubicin Hydr... Multigated Acqu... Pembrolizumab Punch Biopsy	18 Years - 75 Years	National Cancer Institute (NCI)
A Study of Venetoclax in Combination With Conventional Chemotherapy in Pediatric Patients With Acute Myeloid Leukemia	NCT05955261	Acute Myeloid L...	Venetoclax Azacitidine Cytarabine Gemtuzumab Ozog... Daunorubicin Hy... Fludarabine Pho... Idarubicin Hydr... Mitoxantrone Hy... Etoposide Gilteritinib	29 Days - 21 Years	St. Jude Children's Research Hospital
Pomalidomide After Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome	NCT02029950	Acute Myeloid L... Chronic Myelomo... High Risk Myelo... Myeloproliferat...	Cytarabine Daunorubicin Hy... Etoposide Idarubicin Hydr... Laboratory Biom... Pharmacological... Pomalidomide	18 Years - 65 Years	National Cancer Institute (NCI)

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