Ignite Creation Date:
2024-05-05 @ 11:41 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00107354
Status:
COMPLETED
Last Update Posted:
2010-09-20
First Post:
2005-04-05
Brief Title:
Cellular Adoptive Immunotherapy in Treating Patients With Acute Myeloid Leukemia Acute Lymphoblastic Leukemia or Myelodysplastic Syndromes That Relapsed After Donor Stem Cell Transplant
Sponsor:
Fred Hutchinson Cancer Center
Organization:
Fred Hutchinson Cancer Center
Study Overview
Official Title:
Phase I Study of Adoptive Immunotherapy With CD8 Minor Histocompatibility H Antigen-Specific CTL Clones for Patients With Relapsed of AML or ALL After Allogeneic Hematopoietic Stem Cell Transplant
Status:
COMPLETED
Status Verified Date:
2010-09
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:
RATIONALE Biological therapies such as cellular adoptive immunotherapy stimulate the immune system in different ways and stop cancer cells from growing
PURPOSE This phase I trial is studying the side effects of cellular adoptive immunotherapy in treating patients with acute myeloid leukemia acute lymphoblastic leukemia or myelodysplastic syndromes that relapsed after donor stem cell transplant
PURPOSE This phase I trial is studying the side effects of cellular adoptive immunotherapy in treating patients with acute myeloid leukemia acute lymphoblastic leukemia or myelodysplastic syndromes that relapsed after donor stem cell transplant
Detailed Description:
OBJECTIVES
Primary
Determine the toxic effects of adoptive immunotherapy comprising CD8-positive minor histocompatability antigen-specific cytotoxic T-lymphocytes in patients with acute myeloid leukemia acute lymphoblastic leukemia or myelodysplastic syndromes that relapsed after allogeneic hematopoietic stem cell transplantation
Secondary
Determine the persistence of adoptively transfused T cells in vivo and assess their migration to the bone marrow in these patients
Determine the anti-leukemic activity of this therapy in these patients
OUTLINE This is a pilot open-label nonrandomized study
Leukapheresis Patients undergo leukapheresis to obtain peripheral blood mononuclear cells PBMCs before transplantation Donors undergo leukapheresis to obtain PBMCs to use as feeder cells for generating adoptive immunotherapy Patient PBMCs are combined with donor PBMCs and expanded in vitro to generate CD8-positive minor histocompatability antigen-specific cytotoxic T-lymphocytes CTLs for adoptive immunotherapy
Transplantation Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation Patients with a morphologic or flow cytometric relapse on or after day 100 post-transplantation proceed to cytoreductive chemotherapy Patients with a molecular or cytogenetic relapse on or after day 100 post-transplantation proceed directly to adoptive immunotherapy Patients with relapsed disease before day 100 post-transplantation are eligible to receive adoptive immunotherapy at a later date provided the patient continues to relapse and CTLs are available
Cytoreductive chemotherapy The chemotherapy regimen for each patient is determined after consideration of prior chemotherapy type of leukemia and other clinical parameters Two regimens to consider are
Mitoxantrone IV and etoposide IV on days -6 to -2
High-dose cytarabine IV over 2 hours twice daily on days -6 -4 and -2 Patients achieving a complete remission after completion of cytoreductive chemotherapy proceed to adoptive immunotherapy
Adoptive immunotherapy Within 2-3 days after completion of cytoreductive chemotherapy patients receive CTLs IV over 1-2 hours on days 0 4 11 21 and 28 in the absence of unacceptable toxicity Patients with evidence of persistent disease on or after day 35 OR relapsed disease after an initial response to CTLs receive a sixth infusion of CTLs followed no more than 24 hours later by interleukin-2 subcutaneously once daily for up 14 total doses in the absence of unacceptable toxicity Patients with subsequent relapsed disease after day 48 may be eligible for retreatment
After completion of study treatment patients are followed with bone marrow aspiration every 3 months for 1 year
PROJECTED ACCRUAL A total of 25-30 patients 10-15 with acute myeloid leukemia or myelodysplastic syndromes AND 10-15 with acute lymphoblastic leukemia will be accrued for this study within 3 years
Primary
Determine the toxic effects of adoptive immunotherapy comprising CD8-positive minor histocompatability antigen-specific cytotoxic T-lymphocytes in patients with acute myeloid leukemia acute lymphoblastic leukemia or myelodysplastic syndromes that relapsed after allogeneic hematopoietic stem cell transplantation
Secondary
Determine the persistence of adoptively transfused T cells in vivo and assess their migration to the bone marrow in these patients
Determine the anti-leukemic activity of this therapy in these patients
OUTLINE This is a pilot open-label nonrandomized study
Leukapheresis Patients undergo leukapheresis to obtain peripheral blood mononuclear cells PBMCs before transplantation Donors undergo leukapheresis to obtain PBMCs to use as feeder cells for generating adoptive immunotherapy Patient PBMCs are combined with donor PBMCs and expanded in vitro to generate CD8-positive minor histocompatability antigen-specific cytotoxic T-lymphocytes CTLs for adoptive immunotherapy
Transplantation Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation Patients with a morphologic or flow cytometric relapse on or after day 100 post-transplantation proceed to cytoreductive chemotherapy Patients with a molecular or cytogenetic relapse on or after day 100 post-transplantation proceed directly to adoptive immunotherapy Patients with relapsed disease before day 100 post-transplantation are eligible to receive adoptive immunotherapy at a later date provided the patient continues to relapse and CTLs are available
Cytoreductive chemotherapy The chemotherapy regimen for each patient is determined after consideration of prior chemotherapy type of leukemia and other clinical parameters Two regimens to consider are
Mitoxantrone IV and etoposide IV on days -6 to -2
High-dose cytarabine IV over 2 hours twice daily on days -6 -4 and -2 Patients achieving a complete remission after completion of cytoreductive chemotherapy proceed to adoptive immunotherapy
Adoptive immunotherapy Within 2-3 days after completion of cytoreductive chemotherapy patients receive CTLs IV over 1-2 hours on days 0 4 11 21 and 28 in the absence of unacceptable toxicity Patients with evidence of persistent disease on or after day 35 OR relapsed disease after an initial response to CTLs receive a sixth infusion of CTLs followed no more than 24 hours later by interleukin-2 subcutaneously once daily for up 14 total doses in the absence of unacceptable toxicity Patients with subsequent relapsed disease after day 48 may be eligible for retreatment
After completion of study treatment patients are followed with bone marrow aspiration every 3 months for 1 year
PROJECTED ACCRUAL A total of 25-30 patients 10-15 with acute myeloid leukemia or myelodysplastic syndromes AND 10-15 with acute lymphoblastic leukemia will be accrued for this study within 3 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
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 |
|---|---|---|---|
| CDR0000407784 | None | None | None |