Ignite Creation Date:
2024-05-06 @ 3:11 PM
Last Modification Date:
2024-10-26 @ 1:44 PM
Study NCT ID:
NCT04546399
Status:
SUSPENDED
Last Update Posted:
2024-04-18
First Post:
2020-09-11
Brief Title:
A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia B-ALL
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase 2 Study of Blinatumomab NSC 765986 in Combination With Nivolumab NSC 748726 a Checkpoint Inhibitor of PD-1 in B-ALL Patients Aged 1 to 31 Years Old With First Relapse
Status:
SUSPENDED
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Other - FDA Partial Clinical Hold
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II trial studies the effect of nivolumab in combination with blinatumomab compared to blinatumomab alone in treating patients with B-cell acute lymphoblastic leukemia B-ALL that has come back relapsed Down syndrome patients with relapsed B-ALL are included in this study Blinatumomab is an antibody which is a protein that identifies and targets specific molecules in the body Blinatumomab searches for and attaches itself to the cancer cell Once attached an immune response occurs which may kill the cancer cell Nivolumab is a medicine that may boost a patients immune system Giving nivolumab in combination with blinatumomab may cause the cancer to stop growing for a period of time and for some patients it may lessen the symptoms such as pain that are caused by the cancer
Detailed Description:
PRIMARY OBJECTIVES
I To compare rate of minimal residual disease MRD negative second remission Rem-2 after up to two cycles of reinduction with blinatumomab versus vs blinatumomabnivolumab in Group 1 patients aged 1 to 31 years old with first relapse of CD19 B-ALL
II To compare event-free survival EFS PI EFS post-induction between consolidation with blinatumomab vs blinatumomabnivolumab in Group 3 patients aged 1 to 31 years old with first relapse of CD19 B ALL
SECONDARY OBJECTIVES
I To evaluate the safety and tolerability of blinatumomabnivolumab in patients aged 1 to 31 years old with first relapse of CD19 B ALL
II To compare EFS PI between blinatumomab vs blinatumomabnivolumab in Group 2 patients aged 1 to 31 years old with first relapse of CD19 B ALL
EXPLORATORY OBJECTIVES
I In Group 1 patients compare EFS between blinatumomab monotherapy and blinatumomabnivolumab arms as compared to similar patients treated on the predecessor trial AALL1331
II In Group 1 patients compare toxicity as defined by grade 3 or greater adverse events during the first cycle of blinatumomab or blinatumomabnivolumab to similar patients treated with block 1 of cytotoxic chemotherapy on the predecessor trial AALL1331
III In Group 2 patients with MRD 01 after vincristine sulfate dexamethasone pegylated asparaginase and doxorubicin hydrochloride VXLD compare MRD negative second remission Rem-2 rate after the first cycle of immunotherapy between blinatumomab monotherapy and blinatumomabnivolumab arms
IV In patients with Down syndrome DS with first relapse of B-ALL describe the safety tolerability and efficacy as defined by MRD negative second remission Rem-2 after up to two cycles of blinatumomabnivolumab
V With each Group perform subset analyses of EFS and overall survival OS based on features including degree of marrow disease at relapse age sex body mass index cytogenetics sites of relapse percent peripheral blasts at relapse and absolute lymphocyte count at first relapse
OUTLINE Patients 18 years old with marrow - extramedullary EM relapse of any duration after initial diagnosis or patients 18 years old with marrow - EM relapse 24 months after initial diagnosis are assigned to Group 1 Patients 18 years old with marrow - EM relapse 24 months from initial diagnosis or all isolated extramedullary IEM relapses 1 to 31 years old are assigned to Groups 2-3 re-induction Patients with DS are assigned to Arm G NOTE Patients in Group 1 and DS patients with white blood cells WBC 30000uL CNS 23 disease or testicular disease must first receive 1 of 3 pre-immunotherapy treatments
PRE-IMMUNOTHERAPY TREATMENT FOR PATIENTS WITH WBC 30000uL Patients receive methotrexate MTX intrathecally IT or cytarabine IT or intrathecal triple therapy ITT consisting of MTX hydrocortisone sodium succinate and cytarabine IT at the time of diagnostic lumbar puncture LP or on day 1 if intrathecal therapy is given with relapse diagnostic LP 7 days prior to the start of protocol therapy Patients also receive dexamethasone intravenously IV or orally PO twice daily BID on days 1-5 vincristine sulfate via infusion or IV IV push over 1 minute on day 1 Patients with DS also receive leucovorin calcium PO or IV every 6 hours q6h for 2 doses on day 2 or at 24 and 30 hours after each IT administration Patients should proceed to the next cycle when CNS 1 and no testicular disease is present no sooner than Day 8 and no later than Day 15
PRE-IMMUNOTHERAPY TREATMENT FOR CNS 23 DISEASE Patients receive MTX IT or cytarabine IT twice weekly Q2W for 5-7 doses or Intrathecal Triple Therapy ITT IT Q2W for 3-4 doses until patient is CNS 1 Patients with DS also receive leucovorin calcium PO or IV q6h for 2 doses at 24 and 30 hours after each IT administration Patients should proceed to the next cycle when CNS 1 and no testicular disease is present no sooner than Day 15 and no later than Day 24
PRE-IMMUNOTHERAPY TREATMENT FOR TESTICULAR DISEASE Patients receive MTX IT cytarabine IT or ITT IT on days 1 and 15 day 1 may be omitted if intrathecal therapy is given with relapse diagnostic LP 7 days prior to the start of protocol therapy Patients with DS also receive leucovorin calcium PO or IV q6h for 2 doses on days 2 and 16 or at 24 and 30 hours after each IT administration Males with testicular disease at relapse undergo radiation once daily QD for a total of 12 fractions over 12 days Patients should proceed to the next cycle when CNS 1 and no testicular disease is present no sooner than Day 15 and no later than Day 22
GROUP 1 Patients are randomized to Arm A or Arm B
ARM A Patients receive dexamethasone PO or IV on days 1 and 8 of cycle 1 blinatumomab via continuous IV infusion on days 1-28 of cycles 1-2 MTX IT cytarabine IT or ITT IT on days 1 15 and 36 of cycle 1 MTX cytarabine and ITT on day 1 may be omitted if intrathecal therapy was given 7 days prior to the start of this cycle and MTX IT cytarabine IT or ITT IT on days 15 and 36 of cycle 2 Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity NOTE Patients with MRD 001 after cycle 1 may stop study treatment or may choose to continue to cycle 2 Patients with MRD 001 after cycle 1 proceed to cycle 2
ARM B Patients receive dexamethasone blinatumomab and MTX cytarabine or ITT as in Arm A Patients also receive nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2 Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity NOTE Patients with MRD 001 after cycle 1 may stop study treatment or may choose to continue to cycle 2 Patients with MRD 001 after cycle 1 proceed to cycle 2
GROUPS 2-3 REINDUCTION Patients receive vincristine sulfate via infusion or IV push over 1 minute on days 1 8 15 and 22 dexamethasone PO or IV on days 1-14 doxorubicin hydrochloride IV over 1-15 minutes on day 1 MTX IT on days 1 8 and 29 day 1 IT may be omitted if intrathecal therapy is given with relapse diagnostic LP 7 days prior to the start of this cycle days 8 and 29 for CNS 12 patients at relapse only pegaspargase intramuscularly IM or IV over 1-2 hours on days 2 and 16 cytarabine IT on days 4 and 11 CNS 2 patients at relapse only then Q2W until 3 consecutive samples are clear of blasts and ITT IT on days 8 15 22 and 29 CNS 3 patients at relapse only Treatment continues in the absence of disease progression or unacceptable toxicity
GROUP 2 The following patients are randomized to Arm C or Arm D 1 1 to 31 years old IEM relapse 18 months from diagnosis regardless of MRD after Re-Induction 2 18 years old with marrow relapse 24 to 36 months from diagnosis regardless of MRD after Re-Induction 3 1 to 31 years old IEM relapse 18 months and MRD 01 after Re-Induction 4 18 years old with marrow relapse 36 months and MRD 01 after Re-Induction
ARM C Patients receive dexamethasone PO or IV on day 1 of cycle 1 blinatumomab via continuous IV infusion on days 1-28 of cycles 1 and 2 and MTX IT on days 1 and 15 of cycles 1 and 2 day 1 may be omitted from cycle 1 if intrathecal MTX is given 7 days prior to the start of cycle 1 Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity NOTE Patients with MRD 001 after cycle 1 may stop study treatment or may choose to continue to cycle 2 Patients with MRD 001 after cycle 1 proceed to cycle 2
ARM D Patients receive dexamethasone blinatumomab and MTX as in Arm C Patients also receive nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2 Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity NOTE Patients with MRD 001 after cycle 1 may stop study treatment or may choose to continue to cycle 2 Patients with MRD 001 after cycle 1 proceed to cycle 2
GROUP 3 The following patients are randomized to Arm E or Arm F 1 1 to 31 years old with IEM relapse 18 months from diagnosis and MRD 01 after Re-Induction 2 18 years old with marrow relapse 36 months from diagnosis and MRD 01 after Re-Induction
ARM E
IMMUNOTHERAPY CYCLES 1-2 Patients receive dexamethasone PO or IV on day 1 of cycle 1 only blinatumomab IV via continuous infusion on days 1-28 and MTX IT on days 1 and 15 day 1 may be omitted from cycle 1 if intrathecal therapy is given 7 days prior to the start of this cycle Immunotherapy Cycles 1-2 alternate with Continuation Cycles 1-2
CONTINUATION CYCLES 1-2 Patients receive dexamethasone PO on days 1-5 vincristine sulfate IV push over 1 minute or via infusion on day 1 mercaptopurine PO on days 1-42 MTX PO on days 8 15 29 and 36 cyclophosphamide IV over 15-30 minutes on days 43 and 50 etoposide IV over 90-120 minutes on days 43 and 50 thioguanine PO once daily QD on days 43-49 and cytarabine IV over 1-30 minutes or subcutaneously SC on days 44-47 and 51-54 CNS 12 patients at relapse also receive MTX IT on days 1 and 43 and PO q6h for 4 doses on day 22 and leucovorin calcium PO q6h for 2 doses on day 24 CNS 3 patients at relapse also receive ITT IT on days 1 and 43 intermediate dose MTX IV over 36 hours on day 22 and leucovorin calcium IV or PO q6h on days 24 and 25 Treatment repeats every 8 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity
IMMUNOTHERAPY CYCLE 3 Patients receive blinatumomab IV via continuous infusion on days 1-28 and MTX IT on days 1 and 15
MAINTENANCE Patients receive dexamethasone PO BID on days 1-5 29-33 and 57-61 vincristine sulfate IV push over 1 minute or via infusion on days 1 29 and 57 mercaptopurine PO on days 1-84 MTX IT on day 1 CNS 12 patients at relapse only ITT IT on day 1 CNS 3 patients at relapse only and MTX PO on days 8 15 22 29 36 43 50 57 64 71 and 78 Treatment repeats every 12 weeks for 2 years from the start of Re-Induction therapy in the absence of disease progression or unacceptable toxicity
MAINTENANCE CHEMORADIATION FOR CNS 3 PATIENTS ONLY Beginning between the first and second cycles of maintenance therapy patients receive dexamethasone PO BID on days 1-7 and 15-21 vincristine sulfate IV push over 1 minute or via infusion on days 1 8 and 15 and pegaspargase IM or IV over 1-2 hours on day 1 Patients with CNS 3 and isolated CNS relapse undergo cranial radiation in the form of 3-dimensional D-conformal radiation therapy CRT over 5 days per week for a total of 10 treatments
ARM F
IMMUNOTHERAPY CYCLES 1-2 Patients receive dexamethasone PO or IV on day 1 of cycle 1 only blinatumomab IV via continuous infusion on days 1-28 nivolumab IV over 30 minutes on days 11-25 of cycle 1 and on days 1 and 15 of cycles 2 and 3 and MTX IT on days 1 and 15 day 1 may be omitted from cycle 1 if intrathecal therapy is given with 7 days prior to the start of this cycle Immunotherapy Cycles 1-2 alternate with Continuation Cycles 1-2
CONTINUATION CYCLES 1-2 Patients receive dexamethasone PO on days 1-5 vincristine sulfate IV push over 1 minute or via infusion on day 1 mercaptopurine PO on days 1-42 MTX PO on days 8 15 29 and 36 cyclophosphamide IV over 15-30 minutes on days 43 and 50 etoposide IV over 90-120 minutes on days 43 and 50 thioguanine PO QD on days 43-49 and cytarabine IV over 1-30 minutes or SC on days 44-47 and 51-54 CNS 12 patients at relapse also receive MTX IT on days 1 and 43 and PO q6h for 4 doses on day 22 and leucovorin calcium PO q6h for 2 doses on day 24 CNS 3 patients at relapse also receive ITT IT on days 1 and 43 intermediate dose MTX IV over 36 hours on day 22 and leucovorin calcium IV or PO q6h on days 24 and 25
IMMUNOTHERAPY CYCLE 3 Patients receive blinatumomab IV via continuous infusion on days 1-28 nivolumab IV over 30 minutes on days 1 and 15 and MTX IT on days 1 and 15
MAINTENANCE Patients receive dexamethasone PO BID on days 1-5 29-33 and 57-61 vincristine sulfate IV push over 1 minute or via infusion on days 1 29 and 57 mercaptopurine PO on days 1-84 MTX IT on day 1 CNS 12 patients at relapse only ITT IT on day 1 CNS 3 patients at relapse only and MTX PO on days 8 15 22 29 36 43 50 57 64 71 78 Treatment repeats every 12 weeks for 2 years from the start of Re-Induction therapy in the absence of disease progression or unacceptable toxicity
MAINTENANCE CHEMORADIATION FOR CNS 3 PATIENTS Beginning between the first and second cycles of maintenance therapy patients receive dexamethasone PO BID on days 1-7 and 15-21 vincristine sulfate IV push over 1 minute or via infusion on days 1 8 and 15 and pegaspargase IM or IV over 1-2 hours on day 1 Patients with CNS 3 and isolated CNS relapse undergo cranial radiation in the form of 3D-CRT over 5 days per week for a total of 10 treatments in the absence of disease progression or unacceptable toxicity
ARM G DS PATIENTS Patients receive dexamethasone PO or IV on days 1 and 8 of cycle 1 only blinatumomab IV via continuous infusion on days 1-28 nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2 and MTX IT cytarabine IT or ITT IT on days 115 and 36 of cycle 1 MTX cytarabine and ITT on day 1 may be omitted if intrathecal therapy was given 7 days prior to the start this cycle 1 MTX IT cytarabine IT or ITT IT on days 15 and 36 of cycle 2 and leucovorin calcium IV or PO q6h for 2 doses on days 2 16 and 37 of cycle 1 and q6h for 2 doses on days 16 and 37 of cycle 2
Patients with MRD 001 are eligible to come off protocol therapy to receive Consolidation therapy at the end of Cycle 1 or may choose to proceed to Arm G Cycle 2
After completion of study treatment patients are followed up every 3 months for 1 year
I To compare rate of minimal residual disease MRD negative second remission Rem-2 after up to two cycles of reinduction with blinatumomab versus vs blinatumomabnivolumab in Group 1 patients aged 1 to 31 years old with first relapse of CD19 B-ALL
II To compare event-free survival EFS PI EFS post-induction between consolidation with blinatumomab vs blinatumomabnivolumab in Group 3 patients aged 1 to 31 years old with first relapse of CD19 B ALL
SECONDARY OBJECTIVES
I To evaluate the safety and tolerability of blinatumomabnivolumab in patients aged 1 to 31 years old with first relapse of CD19 B ALL
II To compare EFS PI between blinatumomab vs blinatumomabnivolumab in Group 2 patients aged 1 to 31 years old with first relapse of CD19 B ALL
EXPLORATORY OBJECTIVES
I In Group 1 patients compare EFS between blinatumomab monotherapy and blinatumomabnivolumab arms as compared to similar patients treated on the predecessor trial AALL1331
II In Group 1 patients compare toxicity as defined by grade 3 or greater adverse events during the first cycle of blinatumomab or blinatumomabnivolumab to similar patients treated with block 1 of cytotoxic chemotherapy on the predecessor trial AALL1331
III In Group 2 patients with MRD 01 after vincristine sulfate dexamethasone pegylated asparaginase and doxorubicin hydrochloride VXLD compare MRD negative second remission Rem-2 rate after the first cycle of immunotherapy between blinatumomab monotherapy and blinatumomabnivolumab arms
IV In patients with Down syndrome DS with first relapse of B-ALL describe the safety tolerability and efficacy as defined by MRD negative second remission Rem-2 after up to two cycles of blinatumomabnivolumab
V With each Group perform subset analyses of EFS and overall survival OS based on features including degree of marrow disease at relapse age sex body mass index cytogenetics sites of relapse percent peripheral blasts at relapse and absolute lymphocyte count at first relapse
OUTLINE Patients 18 years old with marrow - extramedullary EM relapse of any duration after initial diagnosis or patients 18 years old with marrow - EM relapse 24 months after initial diagnosis are assigned to Group 1 Patients 18 years old with marrow - EM relapse 24 months from initial diagnosis or all isolated extramedullary IEM relapses 1 to 31 years old are assigned to Groups 2-3 re-induction Patients with DS are assigned to Arm G NOTE Patients in Group 1 and DS patients with white blood cells WBC 30000uL CNS 23 disease or testicular disease must first receive 1 of 3 pre-immunotherapy treatments
PRE-IMMUNOTHERAPY TREATMENT FOR PATIENTS WITH WBC 30000uL Patients receive methotrexate MTX intrathecally IT or cytarabine IT or intrathecal triple therapy ITT consisting of MTX hydrocortisone sodium succinate and cytarabine IT at the time of diagnostic lumbar puncture LP or on day 1 if intrathecal therapy is given with relapse diagnostic LP 7 days prior to the start of protocol therapy Patients also receive dexamethasone intravenously IV or orally PO twice daily BID on days 1-5 vincristine sulfate via infusion or IV IV push over 1 minute on day 1 Patients with DS also receive leucovorin calcium PO or IV every 6 hours q6h for 2 doses on day 2 or at 24 and 30 hours after each IT administration Patients should proceed to the next cycle when CNS 1 and no testicular disease is present no sooner than Day 8 and no later than Day 15
PRE-IMMUNOTHERAPY TREATMENT FOR CNS 23 DISEASE Patients receive MTX IT or cytarabine IT twice weekly Q2W for 5-7 doses or Intrathecal Triple Therapy ITT IT Q2W for 3-4 doses until patient is CNS 1 Patients with DS also receive leucovorin calcium PO or IV q6h for 2 doses at 24 and 30 hours after each IT administration Patients should proceed to the next cycle when CNS 1 and no testicular disease is present no sooner than Day 15 and no later than Day 24
PRE-IMMUNOTHERAPY TREATMENT FOR TESTICULAR DISEASE Patients receive MTX IT cytarabine IT or ITT IT on days 1 and 15 day 1 may be omitted if intrathecal therapy is given with relapse diagnostic LP 7 days prior to the start of protocol therapy Patients with DS also receive leucovorin calcium PO or IV q6h for 2 doses on days 2 and 16 or at 24 and 30 hours after each IT administration Males with testicular disease at relapse undergo radiation once daily QD for a total of 12 fractions over 12 days Patients should proceed to the next cycle when CNS 1 and no testicular disease is present no sooner than Day 15 and no later than Day 22
GROUP 1 Patients are randomized to Arm A or Arm B
ARM A Patients receive dexamethasone PO or IV on days 1 and 8 of cycle 1 blinatumomab via continuous IV infusion on days 1-28 of cycles 1-2 MTX IT cytarabine IT or ITT IT on days 1 15 and 36 of cycle 1 MTX cytarabine and ITT on day 1 may be omitted if intrathecal therapy was given 7 days prior to the start of this cycle and MTX IT cytarabine IT or ITT IT on days 15 and 36 of cycle 2 Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity NOTE Patients with MRD 001 after cycle 1 may stop study treatment or may choose to continue to cycle 2 Patients with MRD 001 after cycle 1 proceed to cycle 2
ARM B Patients receive dexamethasone blinatumomab and MTX cytarabine or ITT as in Arm A Patients also receive nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2 Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity NOTE Patients with MRD 001 after cycle 1 may stop study treatment or may choose to continue to cycle 2 Patients with MRD 001 after cycle 1 proceed to cycle 2
GROUPS 2-3 REINDUCTION Patients receive vincristine sulfate via infusion or IV push over 1 minute on days 1 8 15 and 22 dexamethasone PO or IV on days 1-14 doxorubicin hydrochloride IV over 1-15 minutes on day 1 MTX IT on days 1 8 and 29 day 1 IT may be omitted if intrathecal therapy is given with relapse diagnostic LP 7 days prior to the start of this cycle days 8 and 29 for CNS 12 patients at relapse only pegaspargase intramuscularly IM or IV over 1-2 hours on days 2 and 16 cytarabine IT on days 4 and 11 CNS 2 patients at relapse only then Q2W until 3 consecutive samples are clear of blasts and ITT IT on days 8 15 22 and 29 CNS 3 patients at relapse only Treatment continues in the absence of disease progression or unacceptable toxicity
GROUP 2 The following patients are randomized to Arm C or Arm D 1 1 to 31 years old IEM relapse 18 months from diagnosis regardless of MRD after Re-Induction 2 18 years old with marrow relapse 24 to 36 months from diagnosis regardless of MRD after Re-Induction 3 1 to 31 years old IEM relapse 18 months and MRD 01 after Re-Induction 4 18 years old with marrow relapse 36 months and MRD 01 after Re-Induction
ARM C Patients receive dexamethasone PO or IV on day 1 of cycle 1 blinatumomab via continuous IV infusion on days 1-28 of cycles 1 and 2 and MTX IT on days 1 and 15 of cycles 1 and 2 day 1 may be omitted from cycle 1 if intrathecal MTX is given 7 days prior to the start of cycle 1 Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity NOTE Patients with MRD 001 after cycle 1 may stop study treatment or may choose to continue to cycle 2 Patients with MRD 001 after cycle 1 proceed to cycle 2
ARM D Patients receive dexamethasone blinatumomab and MTX as in Arm C Patients also receive nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2 Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity NOTE Patients with MRD 001 after cycle 1 may stop study treatment or may choose to continue to cycle 2 Patients with MRD 001 after cycle 1 proceed to cycle 2
GROUP 3 The following patients are randomized to Arm E or Arm F 1 1 to 31 years old with IEM relapse 18 months from diagnosis and MRD 01 after Re-Induction 2 18 years old with marrow relapse 36 months from diagnosis and MRD 01 after Re-Induction
ARM E
IMMUNOTHERAPY CYCLES 1-2 Patients receive dexamethasone PO or IV on day 1 of cycle 1 only blinatumomab IV via continuous infusion on days 1-28 and MTX IT on days 1 and 15 day 1 may be omitted from cycle 1 if intrathecal therapy is given 7 days prior to the start of this cycle Immunotherapy Cycles 1-2 alternate with Continuation Cycles 1-2
CONTINUATION CYCLES 1-2 Patients receive dexamethasone PO on days 1-5 vincristine sulfate IV push over 1 minute or via infusion on day 1 mercaptopurine PO on days 1-42 MTX PO on days 8 15 29 and 36 cyclophosphamide IV over 15-30 minutes on days 43 and 50 etoposide IV over 90-120 minutes on days 43 and 50 thioguanine PO once daily QD on days 43-49 and cytarabine IV over 1-30 minutes or subcutaneously SC on days 44-47 and 51-54 CNS 12 patients at relapse also receive MTX IT on days 1 and 43 and PO q6h for 4 doses on day 22 and leucovorin calcium PO q6h for 2 doses on day 24 CNS 3 patients at relapse also receive ITT IT on days 1 and 43 intermediate dose MTX IV over 36 hours on day 22 and leucovorin calcium IV or PO q6h on days 24 and 25 Treatment repeats every 8 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity
IMMUNOTHERAPY CYCLE 3 Patients receive blinatumomab IV via continuous infusion on days 1-28 and MTX IT on days 1 and 15
MAINTENANCE Patients receive dexamethasone PO BID on days 1-5 29-33 and 57-61 vincristine sulfate IV push over 1 minute or via infusion on days 1 29 and 57 mercaptopurine PO on days 1-84 MTX IT on day 1 CNS 12 patients at relapse only ITT IT on day 1 CNS 3 patients at relapse only and MTX PO on days 8 15 22 29 36 43 50 57 64 71 and 78 Treatment repeats every 12 weeks for 2 years from the start of Re-Induction therapy in the absence of disease progression or unacceptable toxicity
MAINTENANCE CHEMORADIATION FOR CNS 3 PATIENTS ONLY Beginning between the first and second cycles of maintenance therapy patients receive dexamethasone PO BID on days 1-7 and 15-21 vincristine sulfate IV push over 1 minute or via infusion on days 1 8 and 15 and pegaspargase IM or IV over 1-2 hours on day 1 Patients with CNS 3 and isolated CNS relapse undergo cranial radiation in the form of 3-dimensional D-conformal radiation therapy CRT over 5 days per week for a total of 10 treatments
ARM F
IMMUNOTHERAPY CYCLES 1-2 Patients receive dexamethasone PO or IV on day 1 of cycle 1 only blinatumomab IV via continuous infusion on days 1-28 nivolumab IV over 30 minutes on days 11-25 of cycle 1 and on days 1 and 15 of cycles 2 and 3 and MTX IT on days 1 and 15 day 1 may be omitted from cycle 1 if intrathecal therapy is given with 7 days prior to the start of this cycle Immunotherapy Cycles 1-2 alternate with Continuation Cycles 1-2
CONTINUATION CYCLES 1-2 Patients receive dexamethasone PO on days 1-5 vincristine sulfate IV push over 1 minute or via infusion on day 1 mercaptopurine PO on days 1-42 MTX PO on days 8 15 29 and 36 cyclophosphamide IV over 15-30 minutes on days 43 and 50 etoposide IV over 90-120 minutes on days 43 and 50 thioguanine PO QD on days 43-49 and cytarabine IV over 1-30 minutes or SC on days 44-47 and 51-54 CNS 12 patients at relapse also receive MTX IT on days 1 and 43 and PO q6h for 4 doses on day 22 and leucovorin calcium PO q6h for 2 doses on day 24 CNS 3 patients at relapse also receive ITT IT on days 1 and 43 intermediate dose MTX IV over 36 hours on day 22 and leucovorin calcium IV or PO q6h on days 24 and 25
IMMUNOTHERAPY CYCLE 3 Patients receive blinatumomab IV via continuous infusion on days 1-28 nivolumab IV over 30 minutes on days 1 and 15 and MTX IT on days 1 and 15
MAINTENANCE Patients receive dexamethasone PO BID on days 1-5 29-33 and 57-61 vincristine sulfate IV push over 1 minute or via infusion on days 1 29 and 57 mercaptopurine PO on days 1-84 MTX IT on day 1 CNS 12 patients at relapse only ITT IT on day 1 CNS 3 patients at relapse only and MTX PO on days 8 15 22 29 36 43 50 57 64 71 78 Treatment repeats every 12 weeks for 2 years from the start of Re-Induction therapy in the absence of disease progression or unacceptable toxicity
MAINTENANCE CHEMORADIATION FOR CNS 3 PATIENTS Beginning between the first and second cycles of maintenance therapy patients receive dexamethasone PO BID on days 1-7 and 15-21 vincristine sulfate IV push over 1 minute or via infusion on days 1 8 and 15 and pegaspargase IM or IV over 1-2 hours on day 1 Patients with CNS 3 and isolated CNS relapse undergo cranial radiation in the form of 3D-CRT over 5 days per week for a total of 10 treatments in the absence of disease progression or unacceptable toxicity
ARM G DS PATIENTS Patients receive dexamethasone PO or IV on days 1 and 8 of cycle 1 only blinatumomab IV via continuous infusion on days 1-28 nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2 and MTX IT cytarabine IT or ITT IT on days 115 and 36 of cycle 1 MTX cytarabine and ITT on day 1 may be omitted if intrathecal therapy was given 7 days prior to the start this cycle 1 MTX IT cytarabine IT or ITT IT on days 15 and 36 of cycle 2 and leucovorin calcium IV or PO q6h for 2 doses on days 2 16 and 37 of cycle 1 and q6h for 2 doses on days 16 and 37 of cycle 2
Patients with MRD 001 are eligible to come off protocol therapy to receive Consolidation therapy at the end of Cycle 1 or may choose to proceed to Arm G Cycle 2
After completion of study treatment patients are followed up every 3 months for 1 year
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 |
|---|---|---|---|
| U10CA180886 | NIH | CTEP | httpsreporternihgovquickSearchU10CA180886 |
| NCI-2020-06813 | REGISTRY | None | None |
| AALL1821 | OTHER | None | None |
| AALL1821 | OTHER | None | None |