scholarly journals Phase I study of Topotecan, a new topoisomerase I inhibitor, in patients with refractory or relapsed acute leukemia

Blood ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1146-1151
Author(s):  
HM Kantarjian ◽  
M Beran ◽  
A Ellis ◽  
L Zwelling ◽  
S O'Brien ◽  
...  
Keyword(s):  
Partial Response ◽  
Acute Leukemia ◽  
Phase I ◽  
Continuous Infusion ◽  
Phase I Study ◽  
Topoisomerase I ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous ◽  
Dose Limiting Toxicity ◽  
Severe Mucositis

The purpose of this study was to define, in a phase I study in leukemia, the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of Topotecan, a new topoisomerase I (topo I) inhibitor. Topotecan was delivered by a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or relapsed acute leukemia, at doses ranging from 3.5 mg/m2 to 18 mg/m2 per course. Twenty-seven patients were treated, including 17 patients with acute myelogenous or undifferentiated leukemia, 7 with acute lymphocytic leukemia, and 3 with chronic myelogenous leukemia in blastic phase. Severe mucositis was the dose-limiting toxicity occurring in two of five patients treated with Topotecan 11.8 mg/m2 per course; a third patient had prolonged myelosuppression. At the MTD of 10 mg/m2 per course, 1 of 12 patients had severe mucositis and 5 had mild-to- moderate mucositis. Nausea, vomiting, diarrhea, and prolonged myelosuppression were uncommon. Three patients (11%) achieved a complete response, two (7%) had a partial response, and one (4%) had a hematologic improvement. The overall complete plus partial response rate was 19%, and 24% in acute myelogenous or undifferentiated leukemia. A novel in vitro assay that quantifies Topotecan-stabilized topo I-DNA complexes in patient samples was used, which demonstrated heterogeneity in the ability of Topotecan to interact with topo I, the intracellular target of Topotecan. This phase I study defined the MTD of Topotecan to be 10 mg/m2 by continuous infusion over 5 days every 3 to 4 weeks in patients with refractory or relapsed acute leukemia. Severe mucositis was the dose-limiting toxicity. Future studies will define the precise activity of Topotecan in different leukemia subsets, its efficacy in combination with other antileukemic drugs, and correlations between Topotecan-induced topo I-DNA complex formation and individual patient response to Topotecan.

scholarly journals Phase I study of Topotecan, a new topoisomerase I inhibitor, in patients with refractory or relapsed acute leukemia

Blood ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1146-1151 ◽  
Author(s):  
HM Kantarjian ◽  
M Beran ◽  
A Ellis ◽  
L Zwelling ◽  
S O'Brien ◽  
...  
Keyword(s):  
Partial Response ◽  
Acute Leukemia ◽  
Phase I ◽  
Continuous Infusion ◽  
Phase I Study ◽  
Topoisomerase I ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous ◽  
Dose Limiting Toxicity ◽  
Severe Mucositis

Abstract The purpose of this study was to define, in a phase I study in leukemia, the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of Topotecan, a new topoisomerase I (topo I) inhibitor. Topotecan was delivered by a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or relapsed acute leukemia, at doses ranging from 3.5 mg/m2 to 18 mg/m2 per course. Twenty-seven patients were treated, including 17 patients with acute myelogenous or undifferentiated leukemia, 7 with acute lymphocytic leukemia, and 3 with chronic myelogenous leukemia in blastic phase. Severe mucositis was the dose-limiting toxicity occurring in two of five patients treated with Topotecan 11.8 mg/m2 per course; a third patient had prolonged myelosuppression. At the MTD of 10 mg/m2 per course, 1 of 12 patients had severe mucositis and 5 had mild-to- moderate mucositis. Nausea, vomiting, diarrhea, and prolonged myelosuppression were uncommon. Three patients (11%) achieved a complete response, two (7%) had a partial response, and one (4%) had a hematologic improvement. The overall complete plus partial response rate was 19%, and 24% in acute myelogenous or undifferentiated leukemia. A novel in vitro assay that quantifies Topotecan-stabilized topo I-DNA complexes in patient samples was used, which demonstrated heterogeneity in the ability of Topotecan to interact with topo I, the intracellular target of Topotecan. This phase I study defined the MTD of Topotecan to be 10 mg/m2 by continuous infusion over 5 days every 3 to 4 weeks in patients with refractory or relapsed acute leukemia. Severe mucositis was the dose-limiting toxicity. Future studies will define the precise activity of Topotecan in different leukemia subsets, its efficacy in combination with other antileukemic drugs, and correlations between Topotecan-induced topo I-DNA complex formation and individual patient response to Topotecan.

Phase I/II study of idarubicin given with continuous infusion fludarabine followed by continuous infusion cytarabine in children with acute leukemia: a report from the Children's Cancer Group.

1997 ◽  
Vol 15 (8) ◽  
pp. 2780-2785 ◽  
Author(s):  
P A Dinndorf ◽  
V I Avramis ◽  
S Wiersma ◽  
M D Krailo ◽  
W Liu-Mares ◽  
...  
Keyword(s):  
Phase I ◽  
Continuous Infusion ◽  
Phase Ii ◽  
Phase I Study ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
Cancer Group ◽  
Major Toxicity ◽  
Acute Myelogenous ◽  
Refractory Aml

PURPOSE The Children's Cancer Group (CCG) undertook a phase I study (CCG-0922) to determine a tolerable dose of idarubicin given with fludarabine and cytarabine in children with relapsed or refractory leukemia. The phase I study was extended to a limited phase II study to assess the activity of this combination in children with acute myelogenous leukemia (AML). PATIENTS AND METHODS This was a multiinstitutional study within the CCG. Eleven patients were entered onto the phase I study: seven with AML, three with acute lymphoblastic leukemia (ALL), and one with chronic myelogenous leukemia (CML). The maximal-tolerated dose (MTD) of fludarabine and cytarabine determined in a previous study was a fludarabine loading dose (LD) of 10.5 mg/m2 followed by a continuous infusion (CI) of 30.5 mg/m2/24 hours for 48 hours, followed by cytarabine LD 390 mg/m2, then CI 101 mg/m2/h for 72 hours. Idarubicin was given at three dose levels: 6, 9, and 12 mg/m2 intravenously (I.V.) on days 0, 1, and 2. The phase II portion of the trial included 10 additional patients with relapsed or refractory AML. RESULTS A dose of idarubicin 12 mg/m2/d for 3 days given in combination with fludarabine and cytarabine was tolerated. The major toxicity encountered was hematologic. Nonhematologic toxicities included transaminase elevations, hyperbilirubinemia, and infections. Eight of 10 patients with AML in the phase II portion (12 mg/m2 idarubicin) achieved a complete remission (CR). CONCLUSION This combination is active in patients with relapsed or refractory AML. The major toxicity encountered is hematologic. This regimen may be useful therapy for AML and should be compared with standard induction therapy in children with newly diagnosed AML.

A Phase I Study of Temozolomide (Temodar®) in Pediatric Patients with Relapsed or Refractory Leukemia—A Children’s Oncology Group Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4455-4455
Author(s):  
Terzah M. Horton ◽  
Eileen Dolan ◽  
Madhuri Hegde ◽  
Stacey L. Berg ◽  
Peter Adamson ◽  
...  
Keyword(s):  
Phase I ◽  
Microsatellite Instability ◽  
Phase I Study ◽  
Sampling Strategy ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Methyl Transferase ◽  
Starting Dose ◽  
Acute Myelogenous ◽  
Dose Limiting Toxicity

Abstract A phase I study of oral temozolomide, administered daily for 5 days every 28 days, was performed in children with relapsed or primary refractory leukemias. The starting dose was 200 mg/m2/day with subsequent dose escalation to 260 mg/m2/day. Ten patients (5 male, 5 female), median age 9 years (range: 1–18 years), with leukemia (6 with acute lymphocytic leukemia [ALL], 4 with acute myelogenous leukemia [AML]) received a total of 14 cycles of temozolomide. Serum pharmacokinetic (PK) samples were obtained in 6 patients using a limited pharmacokinetic sampling strategy. Samples were also obtained from 8 patients for correlative biology studies, including analysis of methyl-guanine methyl transferase (MGMT) activity and microsatellite instability (MSI). MGMT activity was measured in 7 patients; all 3 patients with ALL tested for MGMT had elevated MGMT activity, with a median MGMT activity of 1240 fmol/mg protein (range: 356–1756). In contrast, 3 out of 4 patients with AML had MGMT activity below the limits of detection. Eight patients were tested for microsatellite instability by multiplex PCR using a panel of 13 MSI loci. Two patients (one with ALL and one with AML) demonstrated probable MSI instability. Temozolomide has been well tolerated, with no patients developing dose-limiting toxicity to date. One patient with AML, undetectable MGMT activity and no microsatellite instability had a partial response (PR) lasting 4 cycles (<10% myeloblasts in bone marrow). Further analysis is underway to determine the frequency of elevated MGMT activity in ALL and AML patients at diagnosis and following relapse.

Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia.

1997 ◽  
Vol 15 (5) ◽  
pp. 1796-1802 ◽  
Author(s):  
S M Kornblau ◽  
E Estey ◽  
T Madden ◽  
H T Tran ◽  
S Zhao ◽  
...  
Keyword(s):  
Phase I ◽  
Acute Myelogenous Leukemia ◽  
Phase I Study ◽  
Quantitative Polymerase Chain Reaction ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Psc 833 ◽  
Mdr1 Expression ◽  
Acute Myelogenous ◽  
Sdz Psc 833

PURPOSE Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.

An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma.

1990 ◽  
Vol 8 (11) ◽  
pp. 1907-1912 ◽  
Author(s):  
R Ohno ◽  
K Okada ◽  
T Masaoka ◽  
A Kuramoto ◽  
T Arima ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Phase Ii ◽  
Early Phase ◽  
Topoisomerase I ◽  
Phase Ii Study ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
Cross Resistance ◽  
Treatment Schedule ◽  
Acute Myelogenous

An early phase II study of a new camptothecin analog and an inhibitor of topoisomerase I, CPT-11, was conducted in 62 patients with refractory leukemia and lymphoma by four different treatment schedules in a multiinstitutional cooperative study. CPT-11 therapy resulted in four complete remissions (CRs) and three partial remissions (PRs) in 29 assessable non-Hodgkin's lymphoma (NHL) patients, one PR in three Hodgkin's disease (HD), one CR and one PR in 11 acute lymphoblastic leukemia (ALL), and one PR in 15 acute myelogenous leukemia (AML) patients. Single infusion of 200 mg/m2 every 3 to 4 weeks produced no response in both leukemia and lymphoma patients. Sixty-minute infusions of 40 mg/m2/d for 5 days every 3 to 4 weeks or for 3 days weekly produced four CRs (17%) and four PRs (17%) in 24 patients with malignant lymphoma. Sixty-minute infusions of 20 mg/m2 twice a day for 7 days every 3 to 4 weeks resulted in one CR and two PRs in 12 patients with acute leukemia. No response was seen in an acute leukemia patient by another treatment schedule. CPT-11 was effective in two (15%) of 13 primarily refractory leukemia and lymphoma cases, in two of four relapsed cases, and in seven (17%) of 41 relapsed and refractory cases. Major side effects were leukopenia (91%) and gastrointestinal (GI) (76%). CPT-11 was shown to be effective against refractory leukemia and lymphoma, and thus deserves further clinical study; the novel antitumor activity mode of this drug predicts no cross-resistance to presently available antitumor drugs.

Phase I Study of Temozolomide in Relapsed/Refractory Acute Leukemia

2002 ◽  
Vol 20 (15) ◽  
pp. 3249-3253 ◽  
Author(s):  
Karen Seiter ◽  
Delong Liu ◽  
Thomas Loughran ◽  
Ahmad Siddiqui ◽  
Paul Baskind ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Complete Response ◽  
Hematologic Malignancies ◽  
Maximum Tolerated Dose ◽  
Myelogenous Leukemia ◽  
Platelet Recovery ◽  
Acute Myelogenous ◽  
Dose Limiting Toxicity

PURPOSE: To determine the dose-limiting toxicity and maximum-tolerated dose of temozolomide in patients with acute leukemia. PATIENTS AND METHODS: Twenty patients (16 with acute myelogenous leukemia, two with acute lymphoblastic leukemia, and two with chronic myelogenous leukemia in blastic phase) received 43 cycles of temozolomide. Patients began treatment at two different dose levels: 200 mg/m2/d for 7 days or 200 mg/m2/d for 9 days. RESULTS: Prolonged aplasia was the dose-limiting toxicity, and the maximum-tolerated dose was 7 days of temozolomide. Overall treatment was well tolerated: hospitalization was required in only nine of 43 courses, and there were no treatment-related deaths. Two patients obtained a complete response, and two others met criteria for complete response except for platelet recovery. Overall, nine of 20 patients had a significant decrease in bone marrow blasts after temozolomide treatment. CONCLUSION: Temozolomide was well tolerated and had significant antileukemic activity when administered as a single agent. Further studies of temozolomide in hematologic malignancies are indicated.

High-dose ifosfamide with mesna uroprotection: a phase I study.

1990 ◽  
Vol 8 (1) ◽  
pp. 170-178 ◽  
Author(s):  
A D Elias ◽  
J P Eder ◽  
T Shea ◽  
C B Begg ◽  
E Frei ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
Continuous Infusion ◽  
Dose Level ◽  
Phase I Study ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
Autologous Bone ◽  
Dose Limiting Toxicity ◽  
Cns Toxicity

Phase II trials of ifosfamide have been performed with standard doses of 5 to 8 g/m2/course. In this phase I study, 29 patients were treated with a 4-day continuous infusion ifosfamide to determine the maximum-tolerated dose and the nonhematologic dose-limiting toxicity. Autologous bone marrow support was to have been used for the subsequent dose level if granulocytes were more than 500/microL for more than 14 days in two of two to five patients at a given dose level. Doses were escalated from 8 to 18 g/m2 ifosfamide. Mesna was given at an equivalent dose by continuous infusion for 5 days. At the 18 g/m2 dose level, dose-limiting renal insufficiency and a median of 11 days (range, 8 to 18 days) of granulocytopenia (less than 500/microL) were observed. Thus, autologous bone marrow reinfusion ws not used. The duration of myelosuppression, the frequency and severity of mucositis, and renal tubular acidosis were all dose-dependent. Mild to moderate CNS toxicity also appeared to be related to dose; however, severe CNS toxicity (transient confusion, hallucinations, and somnolence) was observed sporadically at both low- and high-dose levels. Transient hematuria (greater than 50 red blood cells [RBCs]/high power field) occurred once but did not affect treatment. There were nine responses (two complete) in 27 heavily pretreated assessable patients including seven responses in 20 patients with advanced refractory sarcoma. Ifosfamide with mesna uroprotection can undergo considerable dose escalation over the usual prescribed doses before nonhematologic dose-limiting toxicity is encountered. Ifosfamide has broad cytotoxicity against solid tumors and may prove to be an important addition to high-dose combination chemotherapy regimens.

A Phase I Study of Oral 6-Thioguanine, Followed by Continuous Infusion Cytarabine, Followed by Intramuscular PEG-Asparaginase (“TGAP”) in Children with Relapsed or Refractory Acute Leukemia or Non-Hodgkin’s Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4536-4536
Author(s):  
Cecilia H. Fu ◽  
Janet L. Franklin ◽  
Paul Gaynon ◽  
Colleen McCarthy ◽  
Edward Panosyan ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase I ◽  
Continuous Infusion ◽  
Cell Lines ◽  
Dose Level ◽  
Phase I Study ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Grade 3 ◽  
Level 2

Abstract Background: We found enhanced cytotoxicity against human leukemia cell lines resistant to cytarabine with the sequence specific three-drug combination, 6-thioguanine (6TG) + cytarabine + PEG-asparaginase (“TGAP”) [Fu et al, Cancer Chemother Pharmacol 48:123–133, 2001] and developed a Phase I study to evaluate TGAP’s feasibility in children with relapsed/refractory leukemia or non-Hodgkin’s lymphoma with marrow involvement. Patients and Methods: Three days of twice daily 6TG was followed by cytarabine @ 487 mg/m2 loading dose and 126 mg/m2/hr by 72-hour continuous infusion. Cytarabine was followed by pegylated asparaginase @ 2,500 units/m2. Complete response (CR) required fewer than 5% marrow blasts with recovery of neutrophils and platelets. Partial response required marrow blasts between 5% and 25% with no peripheral blasts. Results: Between April 1999-January 2006, 11 patients, age 1 to 18 years, were enrolled after local IRB approval and individual or parental informed consent. Six patients had relapsed/refractory ALL, 4 patients had relapsed ANLL (2/4 had Down syndrome) and 1 patient had relapsed Burkitt’s lymphoma/leukemia. Six patients were enrolled at dose level #1 (6TG @ 100mg/m2/dose) and 5 patients were enrolled at dose level #2 (6-TG @ 150mg/m2/dose). The last patient enrolled was later found ineligible, but was included for toxicity. Chemotherapy was well tolerated in 9 patients. All patients developed grade 3–4 neutropenic fevers or bacteremia. Other grade 3–4 toxicities included transient elevations in transaminases. Asparaginase related pancreatitis occurred in two patients, in one with symptoms. Dose limiting acute vascular leak syndrome occurred in two patients at dose level #2 during the cytarabine infusion and just after the completion of therapy. Both required mechanical ventilation but recovered fully. Complete responses (CR) occurred in 2 of 10 evaluable patients and partial response (PR) occurred in 2 for total response rate (CR + PR) of 40%. All four responders tolerated a second course of TGAP. Both CR patients subsequently underwent matched unrelated BMT with no veno-occlusive disease or other excessive toxicity. In one CR patient, ara-CTP incorporation in the patients leukemic blasts ex vivo studied at baseline, pre chemotherapy, and repeated after 6TG and a 24-hour infusion of cytarabine showed a four-fold increase in intracellular ara-CTP, confirming our previous work in cell lines. Conclusions: TGAP is a feasible combination for patients with relapsed leukemias. A phase II study is currently under development using the maximum tolerated dose for 6TG of 100mg/m2/dose in combination with CI ara-C and IM PEG-asparaginase.

Phase I Study of S-trans, Trans-farnesylthiosalicylic Acid (FTS), a Novel Oral Ras Inhibitor, in Patients with Refractory Hematologic Malignancies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1600-1600 ◽  
Author(s):  
Gautam Borthakur ◽  
Farhad Ravandi ◽  
Susan O’Brien ◽  
Miloslav Beran ◽  
Betsy Williams ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Hematologic Malignancies ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Hematologic Toxicity ◽  
Pharmacokinetic Data ◽  
Farnesyl Transferase ◽  
Acute Myelogenous ◽  
American Society

Abstract Background: Ras activation (mutational or non-mutational) is a key pathway for survival and proliferative advantage of leukemic cells. Farnesyl transferase inhibitors (FTI) that are thought to alter lipid modification of Ras and thereby alter its membrane targeting, are in clinical trial in hematologic malignancies but their target may not be specific for Ras. Toxicities of FTIs include diarrhea, skin rash and hepatic toxicity. FTS is an oral Ras inhibitor that causes dislocation of Ras from its membrane location by competing directly with farnesylated Ras to bind to its putative membrane binding proteins. FTS does not inhibit farnesyl transferase enzyme. Methods: We report on an ongoing phase I study of FTS in patients with relapsed/refractory hematologic malignancies in which FTS is administered orally twice daily on days 1–21 of a 28 day cycle in a “3+3” dose escalation design. Results: To date, 18 patients (pts) have been enrolled, with 17 pts treated (1 cycle=2, 2 cycles=8, 4 cycles=2, 5 cycles=1, 6 cycles=2, 8 cycles=1 and 9 cycles=1). Four pts were enrolled at dose level (DL) of 100 mg, 3 pts at each DL of 200, 400, 600 and 800 mg and 2 pts at DL of 900 mg. One pt enrolled at 100 mg DL was never treated. Median age was 72 years (range, 35 to 85 years), median ECOG status 1 (range 0–2) and median no. of prior therapies 2 (range, 0–7). Diagnoses included: Acute myelogenous leukemia (AML) = 9 pts, myelodysplastic syndrome (MDS) = 5 pts, chronic myelomonocytic leukemia (CMML) = 2 pts, chronic myelogenous leukemia (CML) = 1 pt. and Myeloproliferative Disorder = 1 pt. Preliminary analysis of pharmacokinetic data indicates that both Cmax and AUC increase with dose, but less than dose proportionately. Detailed PK data will be available for presentation at the American Society of Hematology 2007 Annual Meeting. Of 17 pts evaluable for response, 7 pts (41%) (4 MDS, 1 CMML, 1 CML, 1 AML) had hematological improvement (HI) (1 in three lineages, 6 in one lineage) without any complete remission. These responses lasted for a median of 9 weeks (range, 4 to 26 weeks). Currently, 2 patients are continuing on study with improvement in cytopenia and stable disease for over 20 weeks each. Grade 1–2 diarrhea has been the only non-hematologic toxicity seen, observed in 14 of 17 (82%) pts evaluable for toxicity and is completely correctable with oral antidiarrheals. Conclusion: FTS shows promising activity in refractory hematologic malignancies and to date has minimal toxicity.

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