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RAD001 Study in Treatment of Relapsed or Refractory Acute Lymphocytic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00968253
First received: August 27, 2009
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
Acute Lymphocytic Leukemia
Drug: Everolimus (RAD001)
Drug: Cyclophosphamide
Drug: Vincristine
Drug: Doxorubicin
Drug: Dexamethasone
Drug: Mesna
Drug: Methotrexate
Drug: Ara-C (Cytarabine)
Drug: Methylprednisone
Drug: G-CSF
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Hyper-CVAD Plus RAD001 (Everolimus) for Patients With Relapsed or Refractory Acute Lymphocytic Leukemia (ALL)

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose [MTD] [ Time Frame: Following each dose cycles (21 days) ] [ Designated as safety issue: Yes ]
  • Dose-limiting toxicity [DLT] [ Time Frame: Continously during each dose cycle (21 days) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Complete and Overall Response Rate [ Time Frame: Up to 20 cycles of study drugs (21 day cycles) or till disease progression ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: November 2009
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus + Hyper-CVAD
First chemotherapy combination is Hyper-CVAD = Cyclophosphamide, Vincristine, Adriamycin (doxorubicin), and Dexamethasone
Drug: Everolimus (RAD001)
Beginning dose of 5 mg tablets every other day by mouth followed by a big glass of water. First dose will occur 1 day before receiving chemotherapy.
Other Name: Afinitor
Drug: Cyclophosphamide
300 mg/m^2 intravenous (IV) over 3 hours every 12 hours x 6 doses on Days 1, 2, 3 (total dose 1800 mg/m2).
Other Names:
  • Cytoxan
  • Neosar
Drug: Vincristine
2 mg IV on Day 4 and Day 11 ± 2 days.
Drug: Doxorubicin
50 mg/m^2 IV over 24 hours via central venous catheter on day 4, after last dose of Cyclophosphamide given.
Other Names:
  • Adriamycin
  • Rubex
Drug: Dexamethasone
40 mg IV or orally daily days 1-4 ± 2 days and days 11-14 ± 2 days.
Other Name: Decadron
Drug: Mesna
600 mg/m^2 IV continuous infusion daily for 24 hours days 1-3.
Other Name: Mesnex
Drug: G-CSF
10 mcg/kg/day (rounded) within 72 ± 48 hours after completion of chemotherapy until neutrophil recovery 1 x 109/L or higher. Pegfilgrastim (given at 6 mg subcutaneous for one dose approximately 24 hours after completion of the chemotherapy) may be substituted for G-CSF.
Other Names:
  • Filgrastim
  • Neupogen
  • Granulocyte Colony Stimulating Factor
Experimental: Everolimus + Methotrexate and Ara-C
Second chemotherapy combination is Methotrexate and Ara-C (cytarabine).
Drug: Everolimus (RAD001)
Beginning dose of 5 mg tablets every other day by mouth followed by a big glass of water. First dose will occur 1 day before receiving chemotherapy.
Other Name: Afinitor
Drug: Methotrexate
200 mg/m^2 IV over 2 hours followed by 800 mg/m^2 IV over 22 hours day 1.
Drug: Ara-C (Cytarabine)
3 gm/m^2 IV over 2 hours every 12 hours for 4 doses on days 2, 3.
Other Names:
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride
Drug: Methylprednisone
50 mg IV over 2 hours approximately every 12 hours for 6 doses days 1-3.
Other Names:
  • Medrol
  • Depo-Medrol
  • Solu-Medrol
Drug: G-CSF
10 mcg/kg/day (rounded) within 72 ± 48 hours after completion of chemotherapy until neutrophil recovery 1 x 109/L or higher. Pegfilgrastim (given at 6 mg subcutaneous for one dose approximately 24 hours after completion of the chemotherapy) may be substituted for G-CSF.
Other Names:
  • Filgrastim
  • Neupogen
  • Granulocyte Colony Stimulating Factor

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 (sirolimus, 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 Association 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 immunization 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00968253

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Novartis
Investigators
Study Chair: Marina Konopleva, MD, PHD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00968253     History of Changes
Other Study ID Numbers: 2009-0100, NCI-2011-01814
Study First Received: August 27, 2009
Last Updated: May 6, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Acute Lymphocytic Leukemia
ALL
Hyper-CVAD
RAD001
Everolimus
6-mercaptopurine
Citrovorum
Cyclophosphamide
Cytarabine
Dexamethasone
Doxorubicin
G-CSF
Methotrexate
MESNA
Pegfilgrastim
Prednisone
Solumedrol
Vincristine Sulfate

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
BB 1101
Cyclophosphamide
Cytarabine
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Doxorubicin
Everolimus
Lenograstim
Liposomal doxorubicin
Methotrexate
Sirolimus
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Adjuvants, Immunologic
Alkylating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on November 20, 2014