MDACC Study Summary 2007-0727

Study Summary
No. 2007-0727:.......Leukemia......Hagop Kantarjian......Leukemia

Study Summary Title



Study Summary Number:	2007-0727

Study Title:	A Randomized Phase II Study of Oral Sapacitabine in Elderly Patients with Acute Myeloid Leukemia Previously Untreated or in First Relapse, or Previously Treated Myelodysplastic Syndrome

Physician

New Patient Referral



Name:	Hagop Kantarjian	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Leukemia	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-7026 Contact us about clinical trials

General Information



Disease Group:	Leukemia	Supported By:	Cyclacel Ltd.

Phase of Study:	Phase II	Return Visit:	Cycle 1, Days 1, 8 and 15 Cycle 2 and subsequent cycles, Day 1 Follow-up visit: 28 days after last dose. (All days + 3 days)

Treatment Agents:	Sapacitabine	Home Care:	Self-medicated

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	NA

Description/
Intervention:

The goal of the first part of this clinical research study is to look at how
well 3 different doses of sapacitabine can help to control AML in patients who
are least 70 years of age or MDS in patients who are at least 60 years of age.
The safety and tolerability of sapacitabine will also be studied.

The main goal of the second part of the study is to learn if sapacitabine can
improve blood cell counts and lower the amount of leukemia in bone marrow.
The main goal of the third and fourth part of this study is to learn which of
the 3 doses of sapacitabine can help to control the disease for at least one
year in patients who are least 70 years of age or older with AML or 60 years of
age or older with MDS.

Study Objectives / Outcomes

The primary objective of Part 1 this study is to evaluate 1-year survival rate of 3 dosing schedules in elderly patients with previously untreated or first relapsed AML or previously treated MDS; the secondary objectives are to assess the number of patients who have achieved a CR, CRp, PR or CRi or hematological improvement and their corresponding durations, transfusion requirements, number of hospitalized days and safety.

The primary objective of Part 2 of this study is to evaluate the rate of clinical benefit response (CR, CRp, PR, major HI or SD) and the rate of complete response (CR or CRp) in elderly patients with previously untreated AML and significant concomitant medical illnesses defined as having a HCTCI of 2 or higher; the secondary objectives are to assess response duration, transfusion requirements, number of hospitalized days, overall survival, and safety.

The primary objective of Part 3 of this study is to evaluate 1-year survival rate of 3 dosing schedules in elderly patients with previously untreated AML that evolved from MDS after receiving hypomethylating agents for the preceding MDS; the secondary objectives are to assess the rate of clinical benefit response (CR, CRp, PR, major HI or SD) and their corresponding durations, transfusion requirements, number of hospitalized days and safety.

The primary objective of Part 4 of this study is to evaluate 1-year survival rate of 3 dosing schedules in older patients with MDS previously treated with hypomethylating agents; the secondary objectives are to assess the rate of clinical benefit response (CR, CRp, PR, major HI or SD) and their corresponding durations, transfusion requirements, number of hospitalized days and safety.

Study Status Information



Study Activation / Registration Date:	12/21/2007

IRB Review and Approval Date:	12/21/2007

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Closed

Projected Accrual:	325

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) For Part 1 of the study, a histologically or pathologically confirmed diagnosis of AML based on WHO classification which is previously untreated by systemic therapy or is in first relapse after achieving a complete remission (CR or CRp) to initial induction, consolidation and/or maintenance therapy; a histologically or pathologically confirmed diagnosis of MDS based on French-American-British (FAB) classification with an IPSS score of intermediate-2 or high-risk which has been previously treated with hypomethylating agents.

2) Continued from #1: For Part 2 of the study, a histologically or pathologically confirmed diagnosis of AML based on WHO classification which is previously untreated by systemic therapy in the setting of significant concomitant medical illnesses defined by having a HCTCI of 2 and higher. For Part 3 of the study, a histologically or pathologically confirmed diagnosis of AML preceded by MDS based on WHO classification after receiving hypomethylating agents for the preceding MDS but the newly diagnosed AML has not been treated with any systemic anti-leukemic therapy.

3) Continued from #2: For Part 4 of the study, a histologically or pathologically confirmed diagnosis of MDS based on FAB classification with an IPSS score of intermediate-2 or high- risk and 6 - < 20% blasts in bone marrow which has been previously treated with hypomethylating agents.

4) Age >/= 70 years for AML or >/= 60 years for MDS

5) Eastern Cooperative Oncology Group (ECOG) performance status 0-2

6) Adequate renal function: Creatinine </= 1.5 x ULN

7) Adequate liver function: Total bilirubin or direct bilirubin </= 1.5 x ULN; Alanine aminotransferase (ALT or SGPT) </= 2.5 x institutional upper limit of normal (ULN) or </= 5 x ULN if the liver is involved by tumor

8) Life expectancy reasonably adequate for evaluating the treatment effect

9) Patient must be able to swallow capsules.

10) Patients must be at least 2 weeks from prior systemic therapy for AML or MDS, radiation therapy, major surgery, or other investigational therapy, and have recovered from clinically significant toxicities of these prior treatments. Patients with >/=50,000 WBC in peripheral blood may receive hydroxyurea to control the WBC <50,000 prior to starting sapacitabine if this is considered by the treating physician to be in the best interest of the patient.

11) All men of reproductive potential must agree to practice effective contraception for 4 weeks prior to study entry, during the entire study period and for one month after the study unless documentation of infertility exists.

12) Ability to understand and willingness to sign the informed consent form

Exclusion Criteria:

1) AML is of the sub-type of acute promyelocytic leukemia.

2) For Part 1 of the study, having received more than one induction systemic therapy for AML or having received a standard dose or high dose ara-C containing regimen for MDS; for Part 2 of the study, having received any systemic therapy for AML or having received hypomethylating agents or cytotoxic chemotherapy for the preceding MDS or myeloproliferative diseases (MPD); for Part 3 and 4 of the study, having received a standard dose or high dose ara-C containing regimen for the preceding MDS.

3) Patients with known central nervous system (CNS) involvement by leukemia should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

4) Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, active cancer(s) other than AML or MDS, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patients receiving intravenous antibiotics for infections that are under control may be included in this study.

5) Continued from #4: Active cancer other than AML or MDS refers to cancer that requires systemic chemotherapy, or biological therapy within 6 months of the study entry. Patients who have received only hormonal therapy in the neoadjuvant or adjuvant setting in the past 6 months may participate in this study.

6) Pregnant or lactating women

7) Known to be HIV-positive

Links

Registration Number: NCT00590187
Study Information on Clinical Trials Registry (clinicaltrials.gov)