Pomalidomide After Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
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|ClinicalTrials.gov Identifier: NCT02029950|
Recruitment Status : Active, not recruiting
First Posted : January 8, 2014
Last Update Posted : October 8, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia-2 High Risk Myelodysplastic Syndrome Myeloproliferative Neoplasm||Drug: Cytarabine Drug: Daunorubicin Hydrochloride Drug: Etoposide Drug: Idarubicin Hydrochloride Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Pomalidomide||Phase 1|
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||63 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||December 16, 2013|
|Estimated Primary Completion Date :||July 4, 2020|
Experimental: Treatment (combination chemotherapy, pomalidomide)
See Detailed Description
Drug: Daunorubicin Hydrochloride
Drug: Idarubicin Hydrochloride
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Maximum tolerated dose of pomalidomide, defined as the highest dose at which 0 or 1 dose-limiting toxicities are observed in 6 patients by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (5.0 beginning April 1, 2018) [ Time Frame: Up to 21 days ]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.
- Proportion of toxicities in the expansion cohort graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (5.0 beginning April 1, 2018) [ Time Frame: Up to 2 years ]The proportion of toxicities by type and grade in the expansion cohort will be reported with exact binomial 95% confidence intervals.
- Proportion of patients achieving complete remission, complete remission with incomplete count recovery, or partial remission [ Time Frame: Up to 2 years ]The proportion of patients achieving each category of response will be reported with 95% exact binomial confidence intervals.
- Progression-free survival [ Time Frame: Time from start of treatment to time of progression or relapse or death, assessed up to 2 years ]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.
- Overall survival [ Time Frame: Time of enrollment onto this study to the time of death, assessed up to 2 years ]Standard life table methods will be used to analyze overall survival.
- Change in lymphocyte subpopulations [ Time Frame: Baseline to up to 1 year ]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.
- Change in levels of antigen-specific CD8+ T cell responses [ Time Frame: Baseline to up to 1 year ]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 of minimal residual disease-leukemic stem cells in marrow [ Time Frame: Day 14 ]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.
- Change in level of cereblon expression in acute myeloid leukemia cells and sorted T cells [ Time Frame: Baseline to up to 1 year ]Will examine in relation to clinical parameters as well as T cell reconstitution.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02029950
|United States, Connecticut|
|New Haven, Connecticut, United States, 06520|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|Principal Investigator:||Ivana Gojo||Johns Hopkins University/Sidney Kimmel Cancer Center|