Ignite Creation Date:
2024-05-06 @ 4:36 PM
Last Modification Date:
2024-10-26 @ 2:12 PM
Study NCT ID:
NCT05032183
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-07-03
First Post:
2021-08-23
Brief Title:
Tagraxofusp and Low-Intensity Chemotherapy for the Treatment of CD123 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
Sponsor:
MD Anderson Cancer Center
Organization:
MD Anderson Cancer Center
Study Overview
Official Title:
Phase IbII Study of the Combination of Low-Intensity Chemotherapy and Tagraxofusp in Patients With Acute Lymphoblastic Leukemia ALL
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase IbII trial studies the effects of tagraxofusp and low-intensity chemotherapy in treating patients with CD123 positive acute lymphoblastic leukemia or lymphoblastic lymphoma that has come back relapsed or does not respond to treatment refractory Tagraxofusp consists of human interleukin 3 IL3 linked to a toxic agent called DT388 IL3 attaches to IL3 receptor positive cancer cells in a targeted way and delivers DT388 to kill them Chemotherapy drugs work in different ways to stop the growth of cancer cells either by killing the cells by stopping them from dividing or by stopping them from spreading Giving tagraxofusp with chemotherapy may help control CD123 positive relapsed or refractory acute lymphoblastic leukemia or lymphoblastic lymphoma
Detailed Description:
PRIMARY OBJECTIVE
I To evaluate the overall response rate complete response CR CR with inadequate count recovery CRi of the regimen within 3 cycles
SECONDARY OBJECTIVES
I Evaluate other clinical efficacy endpoints CR rate minimal residual disease MRD negativity duration of response DOR relapse-free survival RFS overall survival OS
II Determine the proportion of patients proceeding to allogeneic stem cell transplantation allo-SCT
III Determine the safety of the combination regimen
EXPLORATORY OBJECTIVES
I To determine CD123 expression levels pre- and post-therapy II To correlate baseline CD123 expression with response rates and duration of response
III To evaluate change in apoptotic protein expression and alterations in cellular signaling pathways using cytometry by time of flight CyTOF
IV To determine baseline gene expression profile in order to identify ALL subtypes and correlate with clinical outcomes and response to single-agent tagraxofusp-erzs tagraxofusp
OUTLINE
TAGRAXOFUSP AND CHEMOTHERAPY PHASE
CYCLE 1 Patients receive tagraxofusp-erzs intravenously IV over 15 minutes on days 1-5
CYCLES 2 AND 4 Patients receive tagraxofusp-erzs IV over 15 minutes on days 1-3 cyclophosphamide IV over 3 hours twice daily BID and mesna IV on days 4-6 vincristine IV over 15 minutes on days 4 and 15 dexamethasone IV over 30 minutes or orally PO on day 4-7 and 14-17 methotrexate intrathecally IT on day 5 and filgrastim-sndz subcutaneously SC or pegfilgrastim SC on day 8 and cytarabine IT on day 10 Patients may receive rituximab IV over 4-6 hours on days 4 and 14
CYCLES 3 AND 5 Patients receive tagraxofusp-erzs IV over 15 minutes on days 1-3 methotrexate IV over 24 hours on day 4 cytarabine IV over 3 hours BID on days 5-6 filgrastim-sndz SC or pegfilgrastim SC on day 6 methotrexate IT and cytarabine IT on day 11 Patients may receive rituximab IV over 4-6 hours on days 4 and 11 Beginning about 12 hours after the day 4 dose of methotrexate patients may also receive leucovorin IV over 15 minutes 4 times a day for about 8 doses
CYCLES 6 AND 8 Patients receive cyclophosphamide IV over 3 hours BID and mesna IV on days 1-3 vincristine IV over 15 minutes on days 1 and 11 dexamethasone IV over 30 minutes or PO on day 1-4 and 11-14 and filgrastim-sndz SC or pegfilgrastim SC on day 5
CYCLES 7 AND 9 Patients receive methotrexate IV over 24 hours on day 1 cytarabine IV over 3 hours BID on days 2-3 and filgrastim-sndz SC or pegfilgrastim SC on day 4 Beginning about 12 hours after the day 1 dose of methotrexate patients may receive leucovorin IV over 15 minutes 4 times a day for about 8 doses
Cycle 1 is 21 days Treatment repeats every 28 days for cycles 2-9 in the absence of disease progression or unacceptable toxicity
TAGRAXOFUSP AND MAINTENANCE PHASE
CYCLES 1-3 5-7 9-11 13-15 Patients receive mercaptopurine PO three time daily TID on days 1-28 prednisone PO once daily QD on day 1-5 methotrexate PO once every week QW and vincristine IV over 15 minutes every 4 weeks
CYCLES 4 8 and 12 Patients receive tagraxofusp-erzs IV over 15 minutes on days 1-5
Treatment repeats every 28 days for 15 cycles in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed up at 30 days and then every 3 months thereafter
I To evaluate the overall response rate complete response CR CR with inadequate count recovery CRi of the regimen within 3 cycles
SECONDARY OBJECTIVES
I Evaluate other clinical efficacy endpoints CR rate minimal residual disease MRD negativity duration of response DOR relapse-free survival RFS overall survival OS
II Determine the proportion of patients proceeding to allogeneic stem cell transplantation allo-SCT
III Determine the safety of the combination regimen
EXPLORATORY OBJECTIVES
I To determine CD123 expression levels pre- and post-therapy II To correlate baseline CD123 expression with response rates and duration of response
III To evaluate change in apoptotic protein expression and alterations in cellular signaling pathways using cytometry by time of flight CyTOF
IV To determine baseline gene expression profile in order to identify ALL subtypes and correlate with clinical outcomes and response to single-agent tagraxofusp-erzs tagraxofusp
OUTLINE
TAGRAXOFUSP AND CHEMOTHERAPY PHASE
CYCLE 1 Patients receive tagraxofusp-erzs intravenously IV over 15 minutes on days 1-5
CYCLES 2 AND 4 Patients receive tagraxofusp-erzs IV over 15 minutes on days 1-3 cyclophosphamide IV over 3 hours twice daily BID and mesna IV on days 4-6 vincristine IV over 15 minutes on days 4 and 15 dexamethasone IV over 30 minutes or orally PO on day 4-7 and 14-17 methotrexate intrathecally IT on day 5 and filgrastim-sndz subcutaneously SC or pegfilgrastim SC on day 8 and cytarabine IT on day 10 Patients may receive rituximab IV over 4-6 hours on days 4 and 14
CYCLES 3 AND 5 Patients receive tagraxofusp-erzs IV over 15 minutes on days 1-3 methotrexate IV over 24 hours on day 4 cytarabine IV over 3 hours BID on days 5-6 filgrastim-sndz SC or pegfilgrastim SC on day 6 methotrexate IT and cytarabine IT on day 11 Patients may receive rituximab IV over 4-6 hours on days 4 and 11 Beginning about 12 hours after the day 4 dose of methotrexate patients may also receive leucovorin IV over 15 minutes 4 times a day for about 8 doses
CYCLES 6 AND 8 Patients receive cyclophosphamide IV over 3 hours BID and mesna IV on days 1-3 vincristine IV over 15 minutes on days 1 and 11 dexamethasone IV over 30 minutes or PO on day 1-4 and 11-14 and filgrastim-sndz SC or pegfilgrastim SC on day 5
CYCLES 7 AND 9 Patients receive methotrexate IV over 24 hours on day 1 cytarabine IV over 3 hours BID on days 2-3 and filgrastim-sndz SC or pegfilgrastim SC on day 4 Beginning about 12 hours after the day 1 dose of methotrexate patients may receive leucovorin IV over 15 minutes 4 times a day for about 8 doses
Cycle 1 is 21 days Treatment repeats every 28 days for cycles 2-9 in the absence of disease progression or unacceptable toxicity
TAGRAXOFUSP AND MAINTENANCE PHASE
CYCLES 1-3 5-7 9-11 13-15 Patients receive mercaptopurine PO three time daily TID on days 1-28 prednisone PO once daily QD on day 1-5 methotrexate PO once every week QW and vincristine IV over 15 minutes every 4 weeks
CYCLES 4 8 and 12 Patients receive tagraxofusp-erzs IV over 15 minutes on days 1-5
Treatment repeats every 28 days for 15 cycles in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed up at 30 days and then every 3 months thereafter
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-2021-08859 | REGISTRY | None | None |
| 2021-0545 | OTHER | M D Anderson Cancer Center | None |