A Pilot Study to Determine the Safety and Tolerability of Sirolimus Given With Hyper-CVAD Chemotherapy
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|ClinicalTrials.gov Identifier: NCT01184885|
Recruitment Status : Completed
First Posted : August 19, 2010
Results First Posted : January 3, 2014
Last Update Posted : December 18, 2017
|Condition or disease||Intervention/treatment||Phase|
|Lymphoid Malignancies (New or Relapsed) Acute Lymphoblastic Leukemia Burkitt Lymphoma Lymphoblastic Lymphoma Mantle Cell Lymphoma Adult T-cell Leukemia/Lymphoma||Drug: Hyper-CVAD Drug: Sirolimus||Early Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||7 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||July 2010|
|Actual Primary Completion Date :||March 2011|
|Actual Study Completion Date :||April 2013|
Experimental: Hyper-CVAD and Sirolimus
Hyper-CVAD and Sirolimus
Sirolimus loading dose of 12mg on day 1 followed by a single daily dose of 4 mg/ day on days 2 through 7 (Cycle A) and on days 2 through 6 (Cycle B)
Other Name: Rapamycin
- Number of Participants With Count Recovery That Allows for Starting a Phase II Study to Evaluate Response Rates and Survival [ Time Frame: 18 months ]
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 (absolute neutrophil count) of > 0.5 x 10^9/L and platelet count > 50 x 10^9/L.
Hyper-CVAD/Rapamycin will be deemed acceptable if it is feasible to administer in 80% or more of subjects.
- Induction Mortality [ Time Frame: 18 months ]Induction mortality. Hyper-CVAD/ Rapamycin will be considered acceptable if induction mortality does not exceed 31% in patients older than 60, or 15% in those younger than 60
- Complete Response [ Time Frame: Every 21 days or as count recovery allows (at least 14 days apart) up to 24 weeks ]
To describe response rates to hyper-CVAD and sirolimus in adults with ALL and other aggressive lymphoid malignancies.
Bone marrow (<5% blasts) with adequate bone marrow cellularity, no evidence of circulating blasts or extramedullary disease and normalization of peripheral blood counts except for platelets (neutrophil count =1,000/µL).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01184885
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Thomas Jefferson University|
|Philadelphia, Pennsylvania, United States, 19107|
|Principal Investigator:||Margaret Kasner, MD||Thomas Jefferson University|