RAD001 Study in Treatment of Relapsed or Refractory Acute Lymphocytic Leukemia

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00968253
• Date of registration: 27/08/2009
• Prospective Registration: Yes
• Primary sponsor: M.D. Anderson Cancer Center
• Public title: RAD001 Study in Treatment of Relapsed or Refractory Acute Lymphocytic Leukemia
• Scientific title: Phase I/II Study of Hyper-CVAD Plus RAD001 (Everolimus) for Patients With Relapsed or Refractory Acute Lymphocytic Leukemia (ALL)
• Date of first enrolment: November 2009
• Target sample size: 24
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00968253
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Marina Konopleva, MD, PHD
• Affiliation: M.D. Anderson Cancer Center

Key inclusion & exclusion 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. Eastern Cooperative Oncology Group (ECOG) performance status
4. Adequate liver function with serum bilirubin alanine aminotransferase (ALT) and aspartate aminotransferase (AST) unless proven to be related to disease infiltration.

5. Adequate renal function with serum creatinine 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 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 mammilian target of rapamycin
(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. Hepatitis B virus (HBV) DNA
and hepatitis C virus (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.



Age minimum: 10 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Acute Lymphocytic Leukemia

Leukemia

Intervention(s)

Drug: Mesna

Drug: Vincristine

Drug: Cyclophosphamide

Drug: Everolimus (RAD001)

Drug: Dexamethasone

Drug: Doxorubicin

Drug: Methotrexate

Drug: Methylprednisone

Drug: G-CSF

Drug: Ara-C (Cytarabine)

Primary Outcome(s)

Maximum Tolerated Dose [MTD] Determination by Number of Participants With Dose Limiting Toxicity (DLT) [Time Frame: Following first two dose cycles (21 days/each), up to 42 days]

Overall Response Rate (OR) Where OR = CR + CRp + CRi [Time Frame: 8 courses of treatment, up to 24 weeks]

Secondary Outcome(s)

Participant Responses by Daily Dose Level Assignment (RAD001 5 mg, 10 mg and MTD 5 mg) [Time Frame: Up to 20 cycles of study drugs (21 day cycles) or till disease progression]

Secondary ID(s)

2009-0100

NCI-2011-01814

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Novartis

Results

• Results available: Yes
• Date Posted: 31/05/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00968253