Back to resultsDose Escalation Trial of WT1-specific Donor-derived T Cells Following T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Relapsed/Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
busulfan
melphalan
fludarabine
anti-thymocyte globulin (ATG)
a T cell depleted stem cell transplant
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring BUSULFAN, FLUDARABINE, G-CSF, MELPHALAN, RABBIT ATG WT1, PEPTIDE SPECIFIC T CELLS, 12-175
Eligibility Criteria
Inclusion Criteria:
Diagnosis:
- Patient must have multiple myeloma that has either relapsed or remains refractory following autologous stem cell transplantation and patients who have plasma cell leukemia at diagnosis.
- Patients with relapsed multiple myeloma following autologous stem cell transplantation who achieved < partial response following additional chemotherapy or who achieved < PR at 3 months following autologous stem cell transplantation and patients with plasma cell leukemia at diagnosis.
DONOR: Patients must have a healthy HLA matched or mismatched related or unrelated donor who is willing to receive G-CSF injections and undergo apheresis for PBSC collection, or undergo a marrow harvesting procedure.
- HLA-matched related and unrelated donors Patients who have an HLA-matched related or unrelated donor are eligible for entry on this protocol. This will include a healthy donor who is genotypically matched at all A, B, C, DRB1 and DQB1 loci, as tested by DNA analysis.
- HLA- mismatched related and unrelated donors
- Patients who do not have an HLA-matched donor but have a related or unrelated donor who have one antigen or one allele mismatch at the HLA A, B, C, DRB1 or DQB1 loci or who have two mismatches, at HLA-DQB1 and at one other locus, will be eligible for entry on this protocol.
The following inclusion criteria are also required:
- Patients should be ≥ 21, < 73 years old.
- Patients may be of either gender or any ethnic background.
- Patients must have a Karnofsky (adult) or Performance Status > 70%
Patients must have adequate organ function measured by:
- Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50% and must improve with exercise.
- Hepatic: < 3x ULN ALT and < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
- Renal: serum creatinine <1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl > 40 ml/min (measured or calculated/estimated) with dose adjustment of Fludarabine for <70ml/min.
- Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)
- Each patient must be willing to participate as a research subject and must sign an informed consent form.
Exclusion Criteria:
- Female patients who are pregnant or breast-feeding
- Active viral, bacterial or fungal infection
- Patient seropositive for HIV-I/II; HTLV -I/II
- Patients who have had a previous malignancy that is not in remission.
- Patients with known hypersensitivity to mouse proteins (murine antibodies in ISOLEX) if receiving SBA-E- bone marrow, or chicken egg products.
Sites / Locations
- Memorial Sloan Kettering Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pts with Mutiple myeloma
Arm Description
Patients will undergo a preparative regimen with busulfan, melphalan, fludarabine, and anti-thymocyte globulin (ATG), and a T cell depleted stem cell transplant from a histocompatible related or unrelated donor. Hematopoietic stem cell donors for this trial will include individuals who are 10/10 HLA matched or one antigen or allele mismatched at the HLA-A, B, C, DRB1 or DQB1 locus, as defined by high resolution methods .Donors who are 8/10 HLA matched with an antigen or allele mismatched at HLA-DQB1 and at one other locus will also be eligible for the trial. The administration of WT1-specific cytotoxic T cells (WT1 CTLs) post transplantation is integrated to induce complete remissions in patients with residual disease and to decrease the rate of relapse following the allogeneic transplant.
Outcomes
Primary Outcome Measures
assess the toxicities
DLT will be defined as a grade III or greater toxicity developing within 3 weeks of the T cell infusion, as graded by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 or new development of grade II-IV acute GVHD within 3 weeks of the T cell infusion that requires treatment with systemic glucocorticosteroids. Patients will be evaluated for 21 days for grade III or greater toxicities.
maximum tolerated dose (MTD)
Patients will also be monitored for secondary or immune-mediated graft rejection and or onset of grade II-IV acute GVHD following the administration of WT1-specific T-cell infusions. Because patients may still have transplantation associated cytopenia or may have residual disease that may be associated with cytopenias, hematologic toxicity will be excluded in assessing DLT. All patients will be observed for a minimum of 3 weeks after the first WT-1 peptide sensitized T-cell infusion before the dose can be escalated.
Secondary Outcome Measures
serologic response
In addition, patients will be monitored for serologic responses of their myelomas. The time at which the response was achieved will be recorded for all patients and summarized by dose level. The data derived from these studies will provide an initial assessment of the effects of the T cell infusions.
survival
To quantitate the number of WT1-specific T cells in the blood and marrow at defined intervals post infusion
Full Information
NCT ID
NCT01758328
First Posted
December 24, 2012
Last Updated
January 3, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT01758328
Brief Title
Dose Escalation Trial of WT1-specific Donor-derived T Cells Following T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Relapsed/Refractory Multiple Myeloma
Official Title
A Phase I Dose Escalation Trial of WT1-specific Donor-derived T Cells Following T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Relapsed/Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 2012 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to test the safety of specialized white cells from the donor at different doses. They are called WT1 sensitized T cells. They have been grown in the lab and are immunized against a protein. The protein is called the Wilms' tumor protein, or WT1. The multiple myeloma cells make and express this protein". The investigators want to learn whether the WT1 sensitized T cells will attach to the protein and kill the myeloma cells. The investigators want to find out what effects, good and/or bad, it has on the patient and multiple myeloma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
BUSULFAN, FLUDARABINE, G-CSF, MELPHALAN, RABBIT ATG WT1, PEPTIDE SPECIFIC T CELLS, 12-175
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Pts with Mutiple myeloma
Arm Type
Experimental
Arm Description
Patients will undergo a preparative regimen with busulfan, melphalan, fludarabine, and anti-thymocyte globulin (ATG), and a T cell depleted stem cell transplant from a histocompatible related or unrelated donor. Hematopoietic stem cell donors for this trial will include individuals who are 10/10 HLA matched or one antigen or allele mismatched at the HLA-A, B, C, DRB1 or DQB1 locus, as defined by high resolution methods .Donors who are 8/10 HLA matched with an antigen or allele mismatched at HLA-DQB1 and at one other locus will also be eligible for the trial. The administration of WT1-specific cytotoxic T cells (WT1 CTLs) post transplantation is integrated to induce complete remissions in patients with residual disease and to decrease the rate of relapse following the allogeneic transplant.
Intervention Type
Drug
Intervention Name(s)
busulfan
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Drug
Intervention Name(s)
fludarabine
Intervention Type
Biological
Intervention Name(s)
anti-thymocyte globulin (ATG)
Intervention Type
Procedure
Intervention Name(s)
a T cell depleted stem cell transplant
Primary Outcome Measure Information:
Title
assess the toxicities
Description
DLT will be defined as a grade III or greater toxicity developing within 3 weeks of the T cell infusion, as graded by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 or new development of grade II-IV acute GVHD within 3 weeks of the T cell infusion that requires treatment with systemic glucocorticosteroids. Patients will be evaluated for 21 days for grade III or greater toxicities.
Time Frame
21 days
Title
maximum tolerated dose (MTD)
Description
Patients will also be monitored for secondary or immune-mediated graft rejection and or onset of grade II-IV acute GVHD following the administration of WT1-specific T-cell infusions. Because patients may still have transplantation associated cytopenia or may have residual disease that may be associated with cytopenias, hematologic toxicity will be excluded in assessing DLT. All patients will be observed for a minimum of 3 weeks after the first WT-1 peptide sensitized T-cell infusion before the dose can be escalated.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
serologic response
Description
In addition, patients will be monitored for serologic responses of their myelomas. The time at which the response was achieved will be recorded for all patients and summarized by dose level. The data derived from these studies will provide an initial assessment of the effects of the T cell infusions.
Time Frame
2 years
Title
survival
Description
To quantitate the number of WT1-specific T cells in the blood and marrow at defined intervals post infusion
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
72 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis:
Patient must have multiple myeloma that has either relapsed or remains refractory following autologous stem cell transplantation and patients who have plasma cell leukemia at diagnosis.
Patients with relapsed multiple myeloma following autologous stem cell transplantation who achieved < partial response following additional chemotherapy or who achieved < PR at 3 months following autologous stem cell transplantation and patients with plasma cell leukemia at diagnosis.
DONOR: Patients must have a healthy HLA matched or mismatched related or unrelated donor who is willing to receive G-CSF injections and undergo apheresis for PBSC collection, or undergo a marrow harvesting procedure.
HLA-matched related and unrelated donors Patients who have an HLA-matched related or unrelated donor are eligible for entry on this protocol. This will include a healthy donor who is genotypically matched at all A, B, C, DRB1 and DQB1 loci, as tested by DNA analysis.
HLA- mismatched related and unrelated donors
Patients who do not have an HLA-matched donor but have a related or unrelated donor who have one antigen or one allele mismatch at the HLA A, B, C, DRB1 or DQB1 loci or who have two mismatches, at HLA-DQB1 and at one other locus, will be eligible for entry on this protocol.
The following inclusion criteria are also required:
Patients should be ≥ 21, < 73 years old.
Patients may be of either gender or any ethnic background.
Patients must have a Karnofsky (adult) or Performance Status > 70%
Patients must have adequate organ function measured by:
Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50% and must improve with exercise.
Hepatic: < 3x ULN ALT and < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
Renal: serum creatinine <1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl > 40 ml/min (measured or calculated/estimated) with dose adjustment of Fludarabine for <70ml/min.
Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)
Each patient must be willing to participate as a research subject and must sign an informed consent form.
Exclusion Criteria:
Female patients who are pregnant or breast-feeding
Active viral, bacterial or fungal infection
Patient seropositive for HIV-I/II; HTLV -I/II
Patients who have had a previous malignancy that is not in remission.
Patients with known hypersensitivity to mouse proteins (murine antibodies in ISOLEX) if receiving SBA-E- bone marrow, or chicken egg products.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sergio Giralt, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center
Learn more about this trial
Dose Escalation Trial of WT1-specific Donor-derived T Cells Following T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Relapsed/Refractory Multiple Myeloma
We'll reach out to this number within 24 hrs