RAD001 in Relapsed or Refractory AML, ALL, CML in Blastic-Phase, Agnogenic Myeloid Metaplasia, CLL, T-Cell Leukemia, or Mantle Cell Lymphoma

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ClinicalTrials.gov Identifier: NCT00081874

Recruitment Status : Completed

First Posted : April 27, 2004

Last Update Posted : March 21, 2012

Sponsor:

Collaborator:

Novartis

Information provided by (Responsible Party):

M.D. Anderson Cancer Center

Study Description

Brief Summary:

The goal of this clinical research study is to find the highest safe dose of RAD001 that can be given as a treatment for leukemia, mantle cell lymphoma, or myelofibrosis. Another goal is to learn how effective the dose that is found is as a treatment.

Condition or disease	Intervention/treatment	Phase
Leukemia Mantle Cell Lymphoma Myelofibrosis	Drug: RAD001	Phase 1 Phase 2

Detailed Description:

RAD001 is a new drug that was designed to block proteins that are important in the development and growth of cancer.

If you are eligible to take part in this study, you will receive treatment with RAD001 by mouth every day for as long as you stay on study. Four weeks (28 days) of treatment is considered one course of therapy. The first 3 to 6 participants on study will receive the lowest dose of RAD001. If that dose is safe, the next group of 3 to 6 patients will receive double the dose as the first 3-6 participants. If that dose is safe, all further participants will start treatment at that dose.

While on study, you will have weekly blood tests (about 2 teaspoons). Bone marrow aspirates and/or biopsies, x-rays and/or scans will be performed every 4-12 weeks and as often as the physician feels it is necessary. A physical exam will be done at Weeks 5, 7, 9, 11 and anytime the physician sees fit. Vital signs will be taken every week.

You may be removed from this study if you don't respond after 4 courses of therapy, intolerable side effects occur, or if the disease worsens. Your dose may be temporarily held or decreased if certain side effects occur. If you are benefitting from the therapy, you may continue on it indefinitely as long as continue to benefit.

Once you come off study, a physical exam, measurement of vital signs, a blood test (about 2 teaspoons), a bone marrow aspirate and/or biopsy, x-rays, and/or scans will be done.

This is an investigational study. The FDA has authorized RAD001 for use in research only. A total of 70 -125 patients will take part in this study. All will be enrolled at M. D. Anderson.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	29 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase I/II Study of RAD001 in Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Chronic Myeloid Leukemia in Blastic-Phase, Agnogenic Myeloid Metaplasia, Chronic Lymphocytic Leukemia, T-Cell Leukemia, or Mantle Cell Lymphoma
Study Start Date :	April 2004
Actual Primary Completion Date :	September 2006
Actual Study Completion Date :	September 2006

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Chronic myeloid leukemia Core binding factor acute myeloid leukemia Cytogenetically normal acute myeloid leukemia Familial acute myeloid leukemia with mutated CEBPA Primary myelofibrosis

MedlinePlus related topics: Leukemia Lymphoma

Drug Information available for: Sirolimus Everolimus Temsirolimus

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Acute Lymphoblastic Leukemia Chronic Myeloid Leukemia Myelofibrosis Mantle Cell Lymphoma Leukemia, T-cell, Chronic Chronic Myeloproliferative Disorders

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: RAD001 Phase I: Participants initially treated with 5 mg RAD001 by mouth daily for 28 days. Phase II: The MTD (either 5mg or 10mg) administered daily until intolerance or failure or lack of response after 4 cycles of therapy. For assessment purposes, each cycle will comprise a 28-day period.	Drug: RAD001 Phase I: Starting dose 5 mg by mouth daily for 28 days. Phase II: Maximum Tolerated Dose (MTD) from Phase I. Other Names: Everolimus Afinitor

Outcome Measures

Primary Outcome Measures :

Maximum Tolerated Dose (MTD) [ Time Frame: 28 days ]
If either 0 of 3 or 1 of 6 patients assigned to receive dose of 10 mg experiences grade 3 or 4 drug related toxicities, then this dose is the MTD. If greater than 2 patients experience grade 3 or 4 toxicities, either in the first 3 patients or in the first 6 patients, then the MTD is 5 mg.

Secondary Outcome Measures :

Objective Response Rate (ORR) [ Time Frame: 28 days ]
Number of participants with objective response includes a partial or complete response divided by the total number of participants.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with advanced, relapsed or refractory: acute leukemias (AML, ALL), MDS, CMML in transformation with greater than or equal to 10% peripheral blood/bone marrow blasts, CML in blastic phase, agnogenic myeloid metaplasia (AMM), CLL, T-cell leukemia, or mantle cell lymphoma.
Serum bilirubin <= 2 mg/dL, SGOT or SGPT < 3 upper limit of normal, serum creatinine <= 2 mg/dL, unless considered due to organ leukemic involvement or Gilbert's syndrome
The effects of RAD001 on the developing human fetus are unknown. For this reason and because inhibitors of mRNA translation are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Patients who have had cytotoxic chemotherapy (other than hydroxyurea or corticosteroids) or radiotherapy within 7 days prior to entering the study.
Patients may not be receiving any other cytotoxic investigational agents.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to RAD001. RAD001 must not be administered to patients with known hypersensitivity to everolimus, sirolimus or to any of its excipients. Excipients include butylated hydroxytoluene, magnesium stearate, hydroxypropylmethyl-cellulose, crospovidone, and lactose.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study because RAD001 has a potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with RAD001, breastfeeding should be discontinued if the mother is treated with RAD001.

Contacts and Locations

Information from the National Library of Medicine

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): NCT00081874

Locations

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United States, Texas
M.D. Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Novartis

Investigators

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Principal Investigator:	Francis J. Giles, MD	UT MD Anderson Cancer Center

More Information

Additional Information:

M.D. Anderson Cancer Center's website This link exits the ClinicalTrials.gov site

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Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00081874 History of Changes
Other Study ID Numbers:	2003-0948
First Posted:	April 27, 2004 Key Record Dates
Last Update Posted:	March 21, 2012
Last Verified:	March 2012

Keywords provided by M.D. Anderson Cancer Center:


Leukemia Mantle cell lymphoma Myelofibrosis Relapsed or Refractory Acute Myeloid Leukemia Acute Lymphocytic Leukemia Chronic Myeloid Leukemia in Blastic-Phase	Agnogenic Myeloid Metaplasia Chronic Lymphocytic Leukemia T-Cell Leukemia RAD001 Everolimus Afinitor

Additional relevant MeSH terms:

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Lymphoma Leukemia Lymphoma, Mantle-Cell Leukemia, T-Cell Blast Crisis Primary Myelofibrosis Metaplasia Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Leukemia, Myeloid Leukemia, Lymphoid	Lymphoma, Non-Hodgkin Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases Leukemia, Myelogenous, Chronic, BCR-ABL Positive Cell Transformation, Neoplastic Carcinogenesis Neoplastic Processes Pathologic Processes Sirolimus Everolimus Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs

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