Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
|ClinicalTrials.gov Identifier: NCT01820624|
Recruitment Status : Completed
First Posted : March 29, 2013
Last Update Posted : April 27, 2017
|Condition or disease||Intervention/treatment||Phase|
|Adult Acute Megakaryoblastic Leukemia (M7) Adult Acute Monoblastic Leukemia (M5a) Adult Acute Monocytic Leukemia (M5b) Adult Acute Myeloblastic Leukemia With Maturation (M2) Adult Acute Myeloblastic Leukemia Without Maturation (M1) Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Acute Myelomonocytic Leukemia (M4) Adult Erythroleukemia (M6a) Adult Pure Erythroid Leukemia (M6b) Recurrent Adult Acute Myeloid Leukemia||Drug: tretinoin Drug: lithium carbonate Other: laboratory biomarker analysis||Phase 1|
I. To determine the safety and maximum tolerated dose of the combination of tretinoin with lithium carbonate in subjects with non promyelocytic acute myeloid leukemia.
I. To describe the dose limiting toxicities associated with the combination of lithium (lithium carbonate) and tretinoin.
II. To determine the ability of lithium to inhibit glycogen synthase kinase-3 (GSK3) activity in circulating acute myeloid leukemia (AML) cells and to enhance the retinoic acid receptor expression.
III. To determine the ability of lithium and tretinoin to induce differentiation and/or growth inhibition of AML cells.
IV. To determine the response rate of acute myeloid treatment to treatment with the combination of Tretinoin and Lithium.
OUTLINE: This is a dose-escalation study of tretinoin.
Patients receive tretinoin orally (PO) every 12 hours on days 1-7 and 15-21 and lithium carbonate PO three times daily (TID) on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Trial of Lithium and Tretinoin for Treatment of Non-Promyelocytic Acute Myeloid Leukemia in Patients Intolerant or Relapsed/Refractory to Standard Chemotherapy.|
|Study Start Date :||April 30, 2013|
|Actual Primary Completion Date :||October 9, 2015|
|Actual Study Completion Date :||November 13, 2015|
Experimental: Treatment (tretinoin, lithium carbonate)
Patients receive tretinoin PO every 12 hours on days 1-7 and 15-21 and lithium carbonate PO TID on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: lithium carbonate
Other: laboratory biomarker analysis
- Maximum tolerated dose of tretinoin when given together with lithium carbonate, defined as the dose level immediately below that at which at least 2/6 subjects experience dose-limiting toxicity (DLT), graded using the NCI CTCAE version 4.0 [ Time Frame: Up to 28 days ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01820624
|United States, Ohio|
|University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44106|
|Principal Investigator:||Paolo Caimi, MD||University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center|