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

NCT00081874 | Completed Phase 1

• 1 other identifier: 2003-0948
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  28 days

Secondary Outcomes (1)

• Objective Response Rate (ORR)

  28 days

Study Arms (1)

RAD001

EXPERIMENTAL

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

Interventions

RAD001 DRUG

Phase I: Starting dose 5 mg by mouth daily for 28 days. Phase II: Maximum Tolerated Dose (MTD) from Phase I.

Also known as: Everolimus, Afinitor

RAD001

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Novartis: collaborator

Study Sites (1)

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M.D. Anderson Cancer Center's website

MeSH Terms

Conditions

Leukemia; Lymphoma, Mantle-Cell; Primary Myelofibrosis; Recurrence; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, T-Cell

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia, B-Cell; Chronic Disease

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Francis J. Giles, MD

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2004
• First Posted: April 27, 2004
• Study Start: April 1, 2004
• Primary Completion: September 1, 2006
• Study Completion: September 1, 2006
• Last Updated: April 27, 2025

Record last verified: 2012-10

Locations

US (1)