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

Acute Lymphoblastic Leukemia Clinical Trial

Official title: A Pilot Study of Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone (Hyper-CVAD) With Sirolimus for the Treatment of Adult Acute Lymphoblastic Leukemia and Aggressive Lymphoid Malignancies

Status Completed

Clinical Trial 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.

Clinical Trial Description

The primary objective of this trial is to characterize the feasibility, safety and tolerability of therapy with Hyper-CVAD and Rapamycin in adults with ALL and other aggressive lymphoid malignancies.

This study will evaluate the effectiveness of Rapamycin given in combination with Hyper-CVAD during A treatment cycles, and Methotrexate and Cytarabine in B treatment cycles. Both cycles will also contain the drug Rituximab if the patient has a B cell type of leukemia or lymphoma.

This combination of drugs are being studied to determine whether or not these drugs will have an effect in treating this disease.

Current therapeutic regimens for induction of remission in ALL are broadly similar. There is no single best regimen for induction therapy. The hyper-CVAD regimen is of particular interest because it does not include asparaginase as part of the therapeutic regimen and the results of induction are similar to other published regimens.

The HyperCVAD regimen with or without rituximab is also an accepted induction regimen for lymphoblastic lymphoma, Burkitt and Burkitt like lymphoma, Mantle Cell Lymphoma, and ALL in the elderly. The regimen has also been used as a salvage regimen in patients with the above diagnoses who have relapsed after another induction regimen.

This trial will add a novel agent, an mTOR inhibitor (MTI), rapamycin, to act synergistically with the HyperCVAD regimen. This is a pilot study, assessing the feasibility, safety and toxicity of this regimen, with an ultimate goal to perform a phase II study to evaluate response rates and survival.

This is a pilot study of the Hyper-CVAD regimen with Rapamycin for the treatment of adults with acute lymphoblastic leukemia or other aggressive lymphoid malignancies. The standard Hyper-CVAD regimen will be used, with the addition of the investigational agent, Rapamycin. Hyper-CVAD alone is one of the current standard induction and salvage regimens used to treat ALL and other aggressive lymphoid malignancies.

Subjects included will have either de novo, relapsed, or refractory ALL or another aggressive lymphoid malignancy.

Chemotherapy will consist of 4 'A' cycles alternating with 4 'B' cycles, every 21 days, or as count recovery allows (at least 14 days apart) as follows: 1A; 1B; 2A; 2B, 3A; 3B; 4A; 4B. This is dependent on white blood cell count recovery. ;

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Adult T-cell Leukemia/Lymphoma
• Burkitt Lymphoma
• Leukemia
• Leukemia, Lymphoid
• Leukemia, T-Cell
• Leukemia-Lymphoma, Adult T-Cell
• Lymphoblastic Lymphoma
• Lymphoid Malignancies (New or Relapsed)
• Lymphoma
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Mantle Cell Lymphoma
• Neoplasms
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

• NCT number: NCT01184885
• Study type: Interventional
• Source: Thomas Jefferson University
• Status: Completed
• Phase: Early Phase 1
• Start date: July 2010
• Completion date: April 2013