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
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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Feasibility of therapy with Hyper-CVAD and Rapamycin
This will be assessed by evaluating the tolerability of this regimen compared to historical controls who received Hyper-CVAD or Hyper-CVAD/ Rituximab regimens. The treatment will be designated feasible for an individual subject if in 80% of chemotherapy cycles the subject has count recovery that allows for starting the subsequent cycle by Day 28. Count recovery is defined as ANC of > 0.5 x 109 AND Platelet count > 50 x 109/L. Hyper-CVAD/Rapamycin will be deemed acceptable if it is feasible to administer in 80% or more of subjects.
Margaret Kasner, MD
Thomas Jefferson University
United States: Institutional Review Board
|University of Pennsylvania||Philadelphia, Pennsylvania 19104|
|Thomas Jefferson University||Philadelphia, Pennsylvania 19107-6541|