search
Back to results

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

Primary Purpose

Leukemia, Mantle Cell Lymphoma, Myelofibrosis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RAD001
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • M.D. Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RAD001

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD)
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)
Number of participants with objective response includes a partial or complete response divided by the total number of participants.

Full Information

First Posted
April 23, 2004
Last Updated
October 11, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
Novartis
search

1. Study Identification

Unique Protocol Identification Number
NCT00081874
Brief Title
RAD001 in Relapsed or Refractory AML, ALL, CML in Blastic-Phase, Agnogenic Myeloid Metaplasia, CLL, T-Cell Leukemia, or Mantle Cell Lymphoma
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 Type
Interventional

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
April 2004 (undefined)
Primary Completion Date
September 2006 (Actual)
Study Completion Date
September 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
Novartis

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Mantle Cell Lymphoma, Myelofibrosis
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RAD001
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
RAD001
Other Intervention Name(s)
Everolimus, Afinitor
Intervention Description
Phase I: Starting dose 5 mg by mouth daily for 28 days. Phase II: Maximum Tolerated Dose (MTD) from Phase I.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Description
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.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
Number of participants with objective response includes a partial or complete response divided by the total number of participants.
Time Frame
28 days

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francis J. Giles, MD
Organizational Affiliation
UT MD Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
M.D. Anderson Cancer Center's website

Learn more about this trial

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

We'll reach out to this number within 24 hrs