Ignite Creation Date:
2024-05-05 @ 11:57 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00186875
Status:
COMPLETED
Last Update Posted:
2017-07-28
First Post:
2005-09-01
Brief Title:
Therapy for Pediatric Relapsed or Refractory Acute Lymphoblastic Leukemia
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
A Study of Therapy for Pediatric Relapsed or Refractory Acute Lymphoblastic Leukemia
Status:
COMPLETED
Status Verified Date:
2017-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The main purpose of this study is to find out how well participants with relapsed or refractory ALL respond to treatment with an etoposide- and teniposide-based induction chemotherapy regimen and what the side effects are
Primary Objectives
To estimate the response rate for patients with refractory or relapsed ALL
To estimate the survival rate of patients with refractory or relapsed ALL treated with risk-directed therapy
Primary Objectives
To estimate the response rate for patients with refractory or relapsed ALL
To estimate the survival rate of patients with refractory or relapsed ALL treated with risk-directed therapy
Detailed Description:
In this study subjects will be divided into high-risk and standard-risk subgroups according to the length of their first remission the type of early cancer cell T or B-cell and the site or sites of disease relapse The remission induction phase the beginning phase of therapy will consist of three blocks of therapy Block A features daily IV low-dose etoposide in combination with cytarabine given by continuous IV weekly vincristine and daily dexamethasone In block B a combination of weekly PEG-asparaginase vincristine and daily dexamethasone will be given Block C will be a combination of high-dose methotrexate high-dose cytarabine and teniposide
There will be two phases of consolidation treatment phase after induction therapy Additional therapy will be given between the two consolidation phases Continuation will consist of eight weekly cycles of chemotherapy Periodic intrathecal therapy medicine given into the spinal fluid will be given throughout the treatment Participants who do not achieve remission absence of leukemia after consolidation will be offered enrollment on St Jude NKEHM protocol NK cell transplant Hematopoietic stem cell transplant HSCT is planned for participants with high risk disease HSCT will be done according to current institutional practice The duration of chemotherapy will be one year for patients with extramedullary outside the bone marrow relapse and two years for all others
Exploratory objectives include
To determine the prevalence of MRD in children undergoing treatment for relapsed ALL and to compare the results to those obtained in children with newly diagnosed ALL
To compare the level of MRD in bone marrow and peripheral blood concomitantly in children undergoing treatment for relapsed ALL
To characterize the gene expression profile of leukemia cells at the time of diagnosis and relapse to improve our understanding of mechanisms of relapse and of the development of drug resistance
To study whether pre-existing or emerging development of serum antibodies to asparaginase is related to hypersensitivity reaction to asparaginase in patient with relapsed ALL
Detailed Description of Treatment Plan
All patients will receive the same remission induction All high-risk patients will be offered HSCT which will be performed after a suitable donor is identified and preferably after MRD becomes negative If they do not have a donor or they refuse HSCT they will continue to receive chemotherapy Standard-risk patients continue chemotherapy if MRD is negative after induction but will be offered HSCT if MRD is 001 after Block C of Induction Those who do not achieve morphological CR after induction will be treated according to the contingency plan
Block A 14 days
Dexamethasone 5 mgm2day days 1-14
Vincristine 15 mgm2 max 2 mg days 1 and 8
Etoposide 25 mgm2 days 1-14
Cytarabine 25 mgm2 days 1-14
All patients will proceed to Block B if the clinical condition permits
CNS prophylaxis IT MHA
CNS-1 At the time of relapse and day 14
CNS-2 and 3 At the time of relapse day 8 and 14
Leucovorin 5 mgm2 5 mg max dose PO 24 and 30 hours after each IT MHA
Block B 15 days
All patients will proceed to Block B immediately after Block A if they are clinically well
Dexamethasone 6 mgm2 Days 1-14
Vincristine 15 mgm2 days 1 and 8
PEG-Asparaginase 2500 unitsm2 days 1 8 and 15
CNS prophylaxis IT MHA CNS-2 or 3 only if necessary
CNS-1 no IT MHA
CNS-2 and 3 day 8 minimum 4 doses and maximum 8 doses during induction
Leucovorin 5 mgm2 5 mg max PO 24 and 30 hours after each IT MHA
Block C 1 day
All patients who received Block B will proceed to Block C when WBC 1000microL ANC 300microL and platelets 50000 microL after recovery from Block B
Methotrexate 8 gmm2 day 1
Cytarabine 1 gm2 at least 24 h after ITHMA day 1
Teniposide 165 mgm2 day 1
CNS prophylaxis IT MHA
CNS-1 at the time of BMA after Block C
CNS-2 and 3 day 1 and 8 These two doses of IT MHA may be omitted if the patient had negative CSF for blasts in the 3 preceding CSF exam and at the time of BMA after Block C regardless of the previous CSF status
Leucovorin 5 mgm2 5 mg maximum dose PO 24 and 30 hours after each IT MHA
Consolidation I
This is a 4-week phase It will be started if WBC 1000microL ANC 500microL and platelets 50000 microL
Week 1 Dex day 1 2 3 PEG VCR Mito day 4
Week 2 Dex day 1 2 3 PEG VCR day 4
Week 3 Dex day 1 2 3 PEG VCR Mito day 4
Week 4 Dex day 1 2 3 PEG VCR day 4
Dexamethasone 8 mgm2day day 1-3
PEG-Asparaginase 2500 unitsm2 IM day 4 each week
Vincristine 2 mgm2 max 2 mg day 4 each week
Mitoxantrone 12 mgm2 day 4 week 1 and 3
Interim Continuation
Week 1
etoposide 300 mgm2 IV 1 dose on day 1
Cyclophosphamide 300 mgm2 IV 1 dose on day 1
Week 2
Methotrexate 40 mgm2 IV 1 dose on day 1
6-mercaptopurine 75 mgm2 PO Days 1 to 7
Week 3
teniposide 150 mgm2 IV 1 dose on day 1
Cytarabine 300 mgm2 IV 1 dose on day 1
Week 4
Dexamethasone 12 mgm2day PO TID Days 1 to 5
Vinblastine 6 mgm2 IV max 10 mg 1 dose on day 1
Consolidation II
Week 1
etoposide 300 mgm2 IV 1 dose on day 1
Cyclophosphamide 300 mgm2 IV 1 dose on day 1
Week 2
Methotrexate 40 mgm2 IV 1 dose on day 1
6-mercaptopurine 75 mgm2 PO Days 1 to 7
Week 3
teniposide 150 mgm2 IV 1 dose on day 1
Cytarabine 300 mgm2 IV 1 dose on day 1
Week 4
Dexamethasone 12 mgm2day PO TID Days 1 to 5
Vinblastine 6 mgm2 IV max 10 mg 1 dose on day 1
Continuation
Week 1
etoposide 300 mgm2 IV 1 dose on day 1
Cyclophosphamide 300 mgm2 IV 1 dose on day 1
Week 2
Methotrexate 40 mgm2 IV 1 dose on day 1
6-mercaptopurine 75 mgm2 PO QHS Days 1 to 7
Week 3
teniposide 150 mgm2 IV 1 dose on day 1
Cytarabine 300 mgm2 IV 1 dose on day 1
Week 4
Dexamethasone 12 mgm2day PO TID Days 1 to 5
Vincristine 2 mgm2 IVmaximum 2mg 1 dose on day 1
Week 5
etoposide 300 mgm2 IV 1 dose on day 1
Cyclophosphamide 300 mgm2 IV 1 dose on day 1
Week 6
Methotrexate 40 mgm2 IV 1 dose on day 1
6-mercaptopurine 75 mgm2 PO QHS Days 1 to 7
Week 7
teniposide 150 mgm2 IV 1 dose on day 1
Cytarabine 300 mgm2 IV 1 dose on day 1
Week 8
Dexamethasone 12 mgm2day PO TID Days 1 to 5
Vinblastine 6 mgm2 IVmax 10 mg 1 dose on day 1
Plan for Stem Cell Transplant
Patients who have positive MRD high-risk or standard-risk at the end of induction or all high-risk patients regardless of MRD are eligible for HSCT
All high-risk patients are eligible for HSCT HSCT will be performed as soon as MRD becomes negative after induction If MRD becomes negative 001 and a donor has not been found the patient will continue chemotherapy phases Consolidation I Interim Continuation etc until a suitable donor is found
Those who have persistent positive MRD 001 after Block C are also eligible for HSCT
All standard-risk patients will continue chemotherapy if MRD is negative 001 after induction
If MRD is positive 001 after Block C of induction they become eligible for HSCT
Standard-risk patients who have no response or progressive disease after Block A and who have positive MRD 001 after Block B will be candidates for HSCT They will be re-evaluated after Block C If MRD after Block C is positive follow the plan above If MRD is negative after Block C the management will be discussed with Transplant Service
Contingency Plan
Patients who do not achieve morphological CR M1 marrow after Induction
If CR M1 marrow is not achieved after Induction patients will proceed to Consolidation I If they do not achieve CR after Consolidation I they will be offered enrollment on the St Jude NKHEM protocol or offered alternative therapy If they do not achieve CR after NKHEM they will come off treatment
Patients who achieve CR but have positive MRD 001 after Block C of induction Become eligible for HSCT Up to two more courses of chemotherapy course 1 and 2 will be given to attempt reducing MRD They will receive HSCT as soon as MRD becomes negative MRD may be repeated every 2-4 weeks as indicated
Standard-risk patients who have positive MRD 001 after Block B will proceed to Block C Patients in this category will become candidates for HSCT but if MRD becomes negative after Block C the management will be discussed with Transplant Service Chemotherapy may be administered to reduce MRD prior to HSCT Patients will be transplanted as soon as the MRD becomes negative
Patients high-risk or standard-risk who achieved CR but have positive MRD 001 after Block C of Induction will become eligible for HSCT Up to two more courses of chemotherapy course 1 and 2 will be given to attempt reducing MRD They will receive HSCT as soon as MRD becomes negative If MRD remains positive after course 2 then they will proceed to HSCT after discussion with Transplant Service
Course 1
Give chemotherapy according to the plan for Consolidation I Start it immediately regardless of CBC BMA will be performed when WBC 1000microL ANC 300microL and platelets 50000microL If MRD is negative they will receive HSCT
Course 2
This course will be given if MRD is positive after Course 1 Patients will be offered enrollment on St Jude NKHEM protocol
If they are still MRD positive after Course 2 patients may receive Interim Continuation Consolidation II and then Continuation until MRD becomes negative or while awaiting HSCT
There will be two phases of consolidation treatment phase after induction therapy Additional therapy will be given between the two consolidation phases Continuation will consist of eight weekly cycles of chemotherapy Periodic intrathecal therapy medicine given into the spinal fluid will be given throughout the treatment Participants who do not achieve remission absence of leukemia after consolidation will be offered enrollment on St Jude NKEHM protocol NK cell transplant Hematopoietic stem cell transplant HSCT is planned for participants with high risk disease HSCT will be done according to current institutional practice The duration of chemotherapy will be one year for patients with extramedullary outside the bone marrow relapse and two years for all others
Exploratory objectives include
To determine the prevalence of MRD in children undergoing treatment for relapsed ALL and to compare the results to those obtained in children with newly diagnosed ALL
To compare the level of MRD in bone marrow and peripheral blood concomitantly in children undergoing treatment for relapsed ALL
To characterize the gene expression profile of leukemia cells at the time of diagnosis and relapse to improve our understanding of mechanisms of relapse and of the development of drug resistance
To study whether pre-existing or emerging development of serum antibodies to asparaginase is related to hypersensitivity reaction to asparaginase in patient with relapsed ALL
Detailed Description of Treatment Plan
All patients will receive the same remission induction All high-risk patients will be offered HSCT which will be performed after a suitable donor is identified and preferably after MRD becomes negative If they do not have a donor or they refuse HSCT they will continue to receive chemotherapy Standard-risk patients continue chemotherapy if MRD is negative after induction but will be offered HSCT if MRD is 001 after Block C of Induction Those who do not achieve morphological CR after induction will be treated according to the contingency plan
Block A 14 days
Dexamethasone 5 mgm2day days 1-14
Vincristine 15 mgm2 max 2 mg days 1 and 8
Etoposide 25 mgm2 days 1-14
Cytarabine 25 mgm2 days 1-14
All patients will proceed to Block B if the clinical condition permits
CNS prophylaxis IT MHA
CNS-1 At the time of relapse and day 14
CNS-2 and 3 At the time of relapse day 8 and 14
Leucovorin 5 mgm2 5 mg max dose PO 24 and 30 hours after each IT MHA
Block B 15 days
All patients will proceed to Block B immediately after Block A if they are clinically well
Dexamethasone 6 mgm2 Days 1-14
Vincristine 15 mgm2 days 1 and 8
PEG-Asparaginase 2500 unitsm2 days 1 8 and 15
CNS prophylaxis IT MHA CNS-2 or 3 only if necessary
CNS-1 no IT MHA
CNS-2 and 3 day 8 minimum 4 doses and maximum 8 doses during induction
Leucovorin 5 mgm2 5 mg max PO 24 and 30 hours after each IT MHA
Block C 1 day
All patients who received Block B will proceed to Block C when WBC 1000microL ANC 300microL and platelets 50000 microL after recovery from Block B
Methotrexate 8 gmm2 day 1
Cytarabine 1 gm2 at least 24 h after ITHMA day 1
Teniposide 165 mgm2 day 1
CNS prophylaxis IT MHA
CNS-1 at the time of BMA after Block C
CNS-2 and 3 day 1 and 8 These two doses of IT MHA may be omitted if the patient had negative CSF for blasts in the 3 preceding CSF exam and at the time of BMA after Block C regardless of the previous CSF status
Leucovorin 5 mgm2 5 mg maximum dose PO 24 and 30 hours after each IT MHA
Consolidation I
This is a 4-week phase It will be started if WBC 1000microL ANC 500microL and platelets 50000 microL
Week 1 Dex day 1 2 3 PEG VCR Mito day 4
Week 2 Dex day 1 2 3 PEG VCR day 4
Week 3 Dex day 1 2 3 PEG VCR Mito day 4
Week 4 Dex day 1 2 3 PEG VCR day 4
Dexamethasone 8 mgm2day day 1-3
PEG-Asparaginase 2500 unitsm2 IM day 4 each week
Vincristine 2 mgm2 max 2 mg day 4 each week
Mitoxantrone 12 mgm2 day 4 week 1 and 3
Interim Continuation
Week 1
etoposide 300 mgm2 IV 1 dose on day 1
Cyclophosphamide 300 mgm2 IV 1 dose on day 1
Week 2
Methotrexate 40 mgm2 IV 1 dose on day 1
6-mercaptopurine 75 mgm2 PO Days 1 to 7
Week 3
teniposide 150 mgm2 IV 1 dose on day 1
Cytarabine 300 mgm2 IV 1 dose on day 1
Week 4
Dexamethasone 12 mgm2day PO TID Days 1 to 5
Vinblastine 6 mgm2 IV max 10 mg 1 dose on day 1
Consolidation II
Week 1
etoposide 300 mgm2 IV 1 dose on day 1
Cyclophosphamide 300 mgm2 IV 1 dose on day 1
Week 2
Methotrexate 40 mgm2 IV 1 dose on day 1
6-mercaptopurine 75 mgm2 PO Days 1 to 7
Week 3
teniposide 150 mgm2 IV 1 dose on day 1
Cytarabine 300 mgm2 IV 1 dose on day 1
Week 4
Dexamethasone 12 mgm2day PO TID Days 1 to 5
Vinblastine 6 mgm2 IV max 10 mg 1 dose on day 1
Continuation
Week 1
etoposide 300 mgm2 IV 1 dose on day 1
Cyclophosphamide 300 mgm2 IV 1 dose on day 1
Week 2
Methotrexate 40 mgm2 IV 1 dose on day 1
6-mercaptopurine 75 mgm2 PO QHS Days 1 to 7
Week 3
teniposide 150 mgm2 IV 1 dose on day 1
Cytarabine 300 mgm2 IV 1 dose on day 1
Week 4
Dexamethasone 12 mgm2day PO TID Days 1 to 5
Vincristine 2 mgm2 IVmaximum 2mg 1 dose on day 1
Week 5
etoposide 300 mgm2 IV 1 dose on day 1
Cyclophosphamide 300 mgm2 IV 1 dose on day 1
Week 6
Methotrexate 40 mgm2 IV 1 dose on day 1
6-mercaptopurine 75 mgm2 PO QHS Days 1 to 7
Week 7
teniposide 150 mgm2 IV 1 dose on day 1
Cytarabine 300 mgm2 IV 1 dose on day 1
Week 8
Dexamethasone 12 mgm2day PO TID Days 1 to 5
Vinblastine 6 mgm2 IVmax 10 mg 1 dose on day 1
Plan for Stem Cell Transplant
Patients who have positive MRD high-risk or standard-risk at the end of induction or all high-risk patients regardless of MRD are eligible for HSCT
All high-risk patients are eligible for HSCT HSCT will be performed as soon as MRD becomes negative after induction If MRD becomes negative 001 and a donor has not been found the patient will continue chemotherapy phases Consolidation I Interim Continuation etc until a suitable donor is found
Those who have persistent positive MRD 001 after Block C are also eligible for HSCT
All standard-risk patients will continue chemotherapy if MRD is negative 001 after induction
If MRD is positive 001 after Block C of induction they become eligible for HSCT
Standard-risk patients who have no response or progressive disease after Block A and who have positive MRD 001 after Block B will be candidates for HSCT They will be re-evaluated after Block C If MRD after Block C is positive follow the plan above If MRD is negative after Block C the management will be discussed with Transplant Service
Contingency Plan
Patients who do not achieve morphological CR M1 marrow after Induction
If CR M1 marrow is not achieved after Induction patients will proceed to Consolidation I If they do not achieve CR after Consolidation I they will be offered enrollment on the St Jude NKHEM protocol or offered alternative therapy If they do not achieve CR after NKHEM they will come off treatment
Patients who achieve CR but have positive MRD 001 after Block C of induction Become eligible for HSCT Up to two more courses of chemotherapy course 1 and 2 will be given to attempt reducing MRD They will receive HSCT as soon as MRD becomes negative MRD may be repeated every 2-4 weeks as indicated
Standard-risk patients who have positive MRD 001 after Block B will proceed to Block C Patients in this category will become candidates for HSCT but if MRD becomes negative after Block C the management will be discussed with Transplant Service Chemotherapy may be administered to reduce MRD prior to HSCT Patients will be transplanted as soon as the MRD becomes negative
Patients high-risk or standard-risk who achieved CR but have positive MRD 001 after Block C of Induction will become eligible for HSCT Up to two more courses of chemotherapy course 1 and 2 will be given to attempt reducing MRD They will receive HSCT as soon as MRD becomes negative If MRD remains positive after course 2 then they will proceed to HSCT after discussion with Transplant Service
Course 1
Give chemotherapy according to the plan for Consolidation I Start it immediately regardless of CBC BMA will be performed when WBC 1000microL ANC 300microL and platelets 50000microL If MRD is negative they will receive HSCT
Course 2
This course will be given if MRD is positive after Course 1 Patients will be offered enrollment on St Jude NKHEM protocol
If they are still MRD positive after Course 2 patients may receive Interim Continuation Consolidation II and then Continuation until MRD becomes negative or while awaiting HSCT
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2011-01256 | REGISTRY | NCI Clinical Trial Registration Program | None |