Return to List

Study Summary
No. 2009-0100:.......Leukemia......Marina Konopleva......Leukemia
.
Study Summary Title
Study Summary
Number:
2009-0100
Study Title:Phase I/II study of Hyper-CVAD plus RAD001 (everolimus) for patients with relapsed or refractory acute lymphocytic leukemia
.
Physician New Patient Referral
Name:Marina KonoplevaPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:LeukemiaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-794-1628
Contact us about clinical trials
.
General Information
Disease Group:LeukemiaSupported By:Novartis
Phase of Study:Phase I/Phase IIReturn
Visit:
1-3 times weekly for course 1, then every 1-2 weeks during course 2-8 if
administered at MDACC. If components of the courses 3-8 and maintenance
chemotherapy are delivered by the local oncologist, the participants must come
to MDACC monthly.
Treatment
Agents:
6-mercaptopurine
Citrovorum
Cyclophosphamide
Cytarabine
Dexamethasone
Doxorubicin
G-CSF
Methotrexate
MESNA
Pegfilgrastim
Prednisone
RAD001
Solumedrol
Vincristine Sulfate
Home Care:RAD001 will be self-administered continuously at home. G-CSF can be
administered at home.
Treatment Loc:Only at MDACC
Estimated
Length of Stay
in Houston:
For hyper-CVAD (odd) courses, 4-5 days; for high-dose methotrexate/cytarabine
(even) courses for 3-4 days. Frequency-approximately every 21-28 days, for 8
courses total.
Description/
Intervention:
The goal of Phase I of this clinical research study is to find the highest
tolerable dose of RAD001 (everolimus) when given in combination with the
standard chemotherapy regimens to patients with ALL.

The goal of Phase II of this study is to learn if the drug combinations can
help to control ALL. The safety of these drug combinations will be also studied
in both phases.
.
Study Objectives / Outcomes
Primary:
To establish the safety (dose-limiting toxicity [DLT] and maximum tolerated dose [MTD]), and efficacy (complete and overall response rate) of the RAD001 in combination with the hyper-CVAD regimen.

Secondary:
To analyze the effects of RAD001 on AKT/mTOR signaling pathways in leukemic blasts.
.
Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:11/18/2009
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Open
Projected Accrual:N/A
.
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) Refractory or relapsed acute lymphocytic leukemia (ALL) or lymphoblastic lymphoma (LL). Patients expressing Philadelphia chromosome (Ph+) are eligible if they have failed a prior tyrosine kinase-containing therapy.

2) Age >/= 10 years.

3) ECOG performance status </= 3.

4) Adequate liver function with serum bilirubin </= 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 2.5 x ULN, unless proven to be related to disease infiltration.

5) Adequate renal function with serum creatinine </= 1.5 x ULN, unless proven to be related to disease infiltration.

6) No symptomatic pulmonary disease. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) >/= 50% of expected, corrected for hemoglobin.

7) Fasting serum cholesterol </= 300 mg/dL (or </= 7.75 mmol/L); fasting triglycerides </= 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.

8) Signed informed consent.

Exclusion Criteria:1) Systemic chemotherapy within 7 days (with the exception of hydroxyurea and/or dexamethasone) prior to starting therapy and recovered from persistent acute toxicity (> grade 1) from that therapy, unless there is evidence of rapidly progressive disease. Concurrent therapy for central nervous system (CNS) prophylaxis or treatment for CNS relapse is permitted.

2) Prior treatment with or known hypersensitivity to an mTOR inhibitor (sirlimus, temsirolimus, everolimus).

3) Major surgery within 4 weeks of start of study drug.

4) Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix, or basal or squamous cell carcinomas of the skin.

5) Severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study: a. Symptomatic congestive heart failure of New York Heart Assocation Class III or IV. b. Unstable angina pectoris or myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia. c. Uncontrolled severe infections. d. Liver disease such as cirrhosis, or severe hepatic impairment (Child-Pugh class C).

6) continuation of #5: Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV DNA and HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.

7) Known history of HIV seropositivity.

8) Impairment of gastrointestinal function of gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, malabsorption syndrome or small bowel resection).

9) Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Childbearing potential is a sexually mature woman who: 1)has not undergone a hysterectomy or bilateral oophorectomy; 2)has not been naturally postmenopausal for at least 24 consecutive months. Adequate contraception must be used throughout the trial and for eight weeks after the last dose of study drug, by both sexes. (Women of child bearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of therapy.)

10) Male patient whose sexual partner(s) are women of child bearing potential who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment.

11) Patients should not receive immunzation with attenuated live vaccines within one week of study entry or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.

12) Patients who have developed pleural effusion while on dasatinib therapy.

.
Links
Registration Number: NCT00968253
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
.
Results


Return to Clinical Trials at M.D. Anderson Cancer Center