A Pilot Study to Determine the Safety and Tolerability of Sirolimus Given With Hyper-CVAD Chemotherapy

• Status: Completed
• Trial end date: 2013-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a pilot study, assessing the feasibility, safety and toxicity of an mTOR (mammalian target of Rapamycin) inhibitor (MTI), rapamycin, when administered with HyperCVAD (Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicine and Dexamethasone), with an ultimate goal to perform a phase II study to evaluate response rates and survival in adults with Acute Lymphoblastic Leukemia (ALL) and aggressive lymphoid malignancies.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Collaborator: American Society of Clinical Oncology
• Treatments: Cyclophosphamide; Doxorubicin; Everolimus; Sirolimus; Vincristine

Criteria

Inclusion Criteria:

1. Patients must have a diagnosis of one of the following lymphoid malignancies (new or relapsed):

• Acute Lymphoblastic Leukemia (B and T cell, Philadelphia Chromosome Negative)

• Burkitt Lymphoma

• Burkitt - type Lymphoma

• Lymphoblastic Lymphoma

• Mantle Cell Lymphoma

• Adult T cell Leukemia/ lymphoma

2. Patients must be >18 years old

3. Patients must have an ECOG performance status of 0 or 1(see attachment 1).

4. Patients must have a life expectancy of at least 4 weeks.

5. Patients must be able to consume oral medication.

6. Patients must have completed any radiotherapy four weeks prior to study entry, 0-2 weeks for local palliative XRT (small port).

7. Patients must have recovered from the toxic effects of any prior chemotherapy to < grade 2 (except alopecia).

8. Required initial laboratory values: Creatinine < or = 2.0mg/dL; total or direct bilirubin < or = 1.5mg/dL (if not due to the leukemia or lymphoma itself); SGPT(ALT) < or = 3xULN; glucose <200 mg/dL, negative pregnancy test for women with child-bearing potential.

9. Patients must be able to sign consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing.

10. Patients may have had a prior stem cell transplant (autologous or allogeneic), however they may not have active GvHD, nor be on any immunosuppression

Exclusion Criteria:

1. Patients must not be receiving any chemotherapy agents (except Hydroxyurea)

2. Intrathecal ARA-C and intrathecal methotrexate are permissible (as they are not systemic and only isolated to the central nervous system).

3. Patients must not be receiving growth factors, except for erythropoietin.

4. Patients with a current second malignancy requiring systemic therapy, other than non-melanoma skin cancers, are not eligible.

5. Patients with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, myocardial infarction within the past 6 months or serious uncontrolled cardiac arrhythmia are not eligible.

6. Patients taking any of the following drugs while on-study are not eligible:

1. Carbamazepine (e.g. Tegretol)

2. Rifabutin (e.g. Mycobutin)

3. Rifampin (e.g. Rifadin)

4. Rifapentine (e.g. Priftin)

5. St. John's Wort- may decrease the effects of sirolimus by decreasing the amount of sirolimus in the body

6. Clarithromycin (e.g. Biaxin)

7. Cyclosporin e.g. (Neorla or Sandimmune)

8. Diltiazem (e.g. Cardizem)

9. Erythromycin (e.g. Akne-Mycin, Ery-Tab)

10. Itraconazole (e.g. Sporanox)

11. Ketoconazole (e.g. Nizoral)

12. Telithromycin (e.g. Ketek)

13. Verapamil (e.g. Calan SR, Isoptin, Verelan)

14. Voriconazole (e.g. VFEND) - May increase the effects of sirolimus by increasing the amount of this medicine in the body. [Cannot be taken within 72 hours prior to or subsequent to receiving rapamycin, but may be taken prior to or after the above time period]

15. Tacrolimus (e.g. Prograf) - May cause liver transplant rejection or serious side effects in patients on sirolimus.

7. Patients with known HIV positivity or AIDS-related illness are not eligible.

8. Patients with other severe concurrent disease which in the judgment of the investigator would make the patient inappropriate for entry into this study are ineligible.

9. Patients must not have evidence of cerebellar dysfunction or prior history of cerebellar dysfunction with Ara-C administration.

10. Patients must not have received any investigational agents within 30 days of study entry.

11. Patients must not be pregnant or breastfeeding. Pregnancy tests must be obtained for all females of child-bearing potential. Pregnant or lactating patients are ineligible for this study due to the unknown human fetal or teratogenic toxicities of rapamycin. Males or females of reproductive age may not participate unless they have agreed to use an effective contraceptive method.

12. Patients who have uncontrolled infection are not eligible. Patients must have any active infections under control. Fungal disease must be stable for at least 2 weeks before study entry. Patients with bacteremia must have documented negative blood cultures prior to study entry.