Pilot Study Of Sirolimus Plus Multiagent Chemotherapy For Relapsed/Refractory Acute Lymphoblastic Leukemia/Lymphoma (SIR-MO-1101)
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|ClinicalTrials.gov Identifier: NCT01658007|
Recruitment Status : Terminated (Slow Accrual)
First Posted : August 6, 2012
Last Update Posted : October 2, 2017
The investigators want to learn about treating relapsed/refractory lymphoblastic leukemia and lymphoma with a drug called sirolimus. The investigators are using sirolimus along with other cancer drugs that are often given to patients with relapsed leukemia and lymphoma.
The main purpose of this study is to determine if sirolimus can be given safely in combination with standard drugs used to treat relapsed lymphoblastic leukemia/lymphoma.
|Condition or disease||Intervention/treatment||Phase|
|Relapsed Lymphoblastic Leukemia Recurrent Adult Lymphoblastic Lymphoma Refractory Acute Lymphoblastic Leukemia Refractory Lymphoblastic Lymphoma||Drug: Sirolimus||Not Applicable|
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You will receive the drug sirolimus in addition to standard chemotherapy drugs.
Just like your original cancer treatment, relapsed leukemia/lymphoma treatment is divided into different parts. You will get sirolimus during the first two parts:
Re-induction: We give chemotherapy drugs to try to put your cancer back into remission, meaning that no cancer cells are found in the bone marrow samples (if you have leukemia) or on imaging studies (if you have lymphoma). From start to finish, this part of therapy lasts 35 days. On this study, you will take the drug sirolimus daily in addition to the normal re-induction chemotherapy drugs. You will swallow liquid sirolimus and you must take it with food. You will take sirolimus three times on the first day and two times each day after that during re-induction.
Altogether, this is the schedule for re-induction:
- Sirolimus by mouth starting 7 days before standard re-induction starts, and continuing every day through day 28
- Mitoxantrone by vein on days 1 and 2
- Vincristine by vein on days 3, 10, 17 and 24
- Dexamethasone by vein or by mouth on days 1-5 and 15-19
- PEG-asparaginase* on days 3 and 17
- IT Methotrexate given in spinal fluid on day 1 (all patients) day 8,29 (if no cancer found in spinal fluid)
- IT Triples given in spinal fluid on days 8,15,22,29 (if cancer found in spinal fluid)
(If you have an allergic reaction to PEG-asparaginase, you may be given 6 doses of Erwinia L-asparaginase instead)
Consolidation: We give drugs to continue to kill cancer cells in your body and prevent them from coming back. From start to finish, this part of therapy will last 63 days (it could be longer if we have to interrupt your treatment because you have low blood counts, and you need to wait for them to come up). On this study, you will take the drug sirolimus daily in addition to the normal consolidation chemotherapy drugs. You will take sirolimus three times on the first day and two times each day after that during consolidation.
Altogether, this is the schedule for consolidation:
- Sirolimus by mouth starting 7 days before consolidation starts, and continuing every day through day 56.
- Cyclophosphamide by vein on days 1 and 29
- Cytarabine by vein or under skin on days 1-4, 8-11, 29-32, 36-39
- 6-mercaptopurine by mouth on days 1-14, 29-42
- PEG-asparaginase* by vein on days 15 and 43
- Vincristine by vein on days 15 and 43
- It Methotrexate in spinal fluid on Days 1 and 29
- After you complete re-induction and consolidation, your doctor will determine the next steps of your treatment. This will depend on how you are doing and it will be up to you and your doctor. It will not be part of this study.
This research only includes the re-induction and consolidation portions of treatment (1 and 2, above). If you have already done re-induction, you can enter the study for consolidation only.
In addition to all the regular tests and procedures done to check on your cancer during this study, we will also take additional blood samples to monitor the levels of sirolimus in your blood (in order to adjust your dose) and we will also take blood samples to find certain markers in your blood that might indicate that the sirolimus is doing what it is supposed to do.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study Of Sirolimus Plus Multiagent Chemotherapy For Relapsed/Refractory Acute Lymphoblastic Leukemia/Lymphoma|
|Study Start Date :||August 2012|
|Actual Primary Completion Date :||January 2017|
|Actual Study Completion Date :||January 2017|
Adding sirolimus to established induction and consolidation chemotherapy for relapsed/refractory acute lymphoblastic leuk
Adding sirolimus to established induction and consolidation chemotherapy for relapsed/refractory acute lymphoblastic leukemia
Other Name: Rapamycin, Rapamune
- Determine rate of dose limiting toxicities [ Time Frame: 35 days ]The safety of the regimen will be assessed by the occurrence of unexpected or severe adverse events attributable to sirolimus
- Number of participants with adverse events to determine maximum tolerated level of sirolimus in combination with chemotherapy [ Time Frame: 28 Days ]MAST (maximum acceptable sirolimus trough) will be the serum trough range at which fewer than one third of patients experience dose limiting toxicities during the observation period (28 days)
- Measure the number of residual leukemia cells in the bone marrow. [ Time Frame: At day 35 of induction and day 56 of consolidation ]Disease response will be assessed according to standard criteria
- Measure protein phosphorylation [ Time Frame: Samples collected at Baseline, Days 1, 3, 8 and 29 of induction and Baseline, and Days 1, 8, 29, and 36. ]Peripheral blood samples (5mL) will be obtained at day -6 (baseline), 1, 3,8, 29 of induction and day -6 (baseline), 1, 8, 29, 36 of consolidation for measurement of pAKT, p-S6, p70S6 kinase activity, and single-cell phosphoflow studies in peripheral blood mononuclear cells
- Tumor measurement by PET and/or CT scan [ Time Frame: After day 35 of induction and/or Day 56 of Consolidation ]Disease response will be assessed according to standard criteria
- Measure changes in sirolimus plasma concentration (ng/ml). [ Time Frame: 56 Days ]Use serial measurements of sirolmus trough levels and PK modeling to adjust individual patient sirolimus dose.
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): NCT01658007
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|Principal Investigator:||Maureen O'Brien, MD||Children's Hospital Medical Center, Cincinnati|