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

NCT01758328 | Completed Phase 1

• 1 other identifier: 12-175
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Keywords

BUSULFAN; FLUDARABINE; G-CSF; MELPHALAN; RABBIT ATG WT1; PEPTIDE SPECIFIC T CELLS; 12-175

Outcome Measures

Primary Outcomes (2)

• 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.

  21 days

• 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.

  1 year

Secondary Outcomes (2)

• serologic response

  2 years

• survival

  2 years

Study Arms (1)

Pts with Mutiple myeloma

EXPERIMENTAL

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.

Drug: busulfan; Drug: melphalan; Drug: fludarabine; Biological: anti-thymocyte globulin (ATG); Procedure: a T cell depleted stem cell transplant

Interventions

busulfan DRUG

Pts with Mutiple myeloma

melphalan DRUG

Pts with Mutiple myeloma

fludarabine DRUG

Pts with Mutiple myeloma

anti-thymocyte globulin (ATG) BIOLOGICAL

Pts with Mutiple myeloma

a T cell depleted stem cell transplant PROCEDURE

Pts with Mutiple myeloma

Eligibility Criteria

• Age: 21 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Busulfan; Melphalan; fludarabine; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Sergio Giralt, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2012
• First Posted: January 1, 2013
• Study Start: December 1, 2012
• Primary Completion: March 17, 2025
• Study Completion: March 17, 2025
• Last Updated: March 20, 2025

Record last verified: 2025-03

Locations

US (1)