Study of Matched Unrelated Donor T Cell Infusion for Hematologic Malignancies After Allo-HSCT

Multiple Myeloma Clinical Trial

Official title:

A Phase I Study of Matched Unrelated Donor BPX-501 T Cell Infusion for Adults With Recurrent or Minimal Residual Disease Hematologic Malignancies Post-Allogeneic Transplant

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02786485
• Other study ID #: BP-008-MUD
• Status: Withdrawn
• Phase: Phase 1
• Start date: May 2016
• Est. completion date: December 2018

Study information

• Verified date: October 2020
• Source: Bellicum Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase I, multicenter, open-label, non-randomized study of matched unrelated donor BPX-501 T cell infusion in adult subjects with hematological malignancies presenting with recurrent disease minimal residual disease (MRD) post-allogeneic transplant.

Description:

Un-manipulated donor lymphocyte infusion (DLI) is used after stem cell transplantation to treat and prevent relapse, to prevent infections and to establish full donor chimerism. The addition of mature T cells which exhibit a broad repertoire of T cell immunity against viral antigens, as well as against cancer antigens, might provide a clinical benefit. However, an expected side effect of the presence of mature T cells is the potential occurrence of acute graft-versus-host disease (aGvHD). The use of a suicide gene switch which would trigger the initiation of the apoptosis of the alloreactive T cells by the infusion of a drug would represent the potential optimal strategy for restoring early immunity with a built in "safety switch" against GvHD side effects. Evidence has emerged that low-dose DLI followed by dose escalation can achieve higher clinical response rate with lower GvHD occurrence. Optimization of DLI dose and schedule as well as strategies of donor T-cell manipulation may lead to the consistent ability to separate GvHD from graft-versus-tumor (GvT) activity and improve the safety of DLI treatment. Our strategy is to infuse escalating doses of manipulated T cells (from the same donor who provided the original hematopoietic stem cell graft) in adults and children with recurrent or minimal residual disease (MRD) hematologic malignancies post-allogeneic transplant to accelerate immune reconstitution thus improving graft versus leukemic effect while reducing the severity of GvHD.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Subjects aged = 18 yrs and = 65 yrs;

• Clinical diagnosis of one of the following hematological malignancies:

• Leukemia

• Myelodysplastic Syndromes

• Lymphomas

• Multiple Myeloma

• Other high-risk hematological malignancy eligible for stem cell transplantation per institutional standard;

• Recurrent disease that presents =100 days after, or minimal residual disease (MRD) that presents = 30 days following a hematopoietic stem cell transplant (HSCT) using a matched unrelated donor located through the National Marrow Donor Program (NMDP);

• Life expectancy >10 weeks;

• Signed donor and patient/guardian informed consent;

• A 8/8 genotypic identical match as determined by high resolution typing for the following genetic loci: human leukocyte antigen (HLA)-A, HLA-B, HLA-C and HLA-DRB1;

• Performance status: Karnofsky score > 50%;

• Subjects with adequate organ function as measured by:

• Bone marrow:

• > 25% donor T-cell chimerism post-transplant

• Absolute neutrophil count (ANC) >1 x 109/L

• Cardiac: left ventricular ejection fraction (LVEF) at rest = 45%

• Pulmonary: forced expiratory volume (FEV) 1, forced vital capacity (FVC), diffusion capacity of lunch for carbon monoxide (DLCO) = 50% predicted (corrected for hemoglobin)

• Hepatic: direct bilirubin = 3x upper limit of normal (ULN), or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) = 5x ULN

• Renal: creatinine = 2x of ULN for age.

Exclusion Criteria:

• = Grade II acute GVHD or chronic extensive GVHD due to a previous allograft at the time of screening;

• Active central nervous system (CNS) involvement with malignant cells (= 2 months prior to consenting);

• Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings); the principal investigator is the final arbiter of this criterion;

• Positive HIV serology or viral RNA;

• Pregnancy (positive serum ß human chorionic gonadotropin [HCG] test) or breast-feeding;

• Fertile men or women unwilling to use effective forms of birth control or abstinence for one year after transplantation;

• Bovine product allergy.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Leukemia
• Lymphomas
• Multiple Myeloma
• Myelodysplastic Syndromes
• Neoplasms
• Other High-risk Hematological Malignancies
• Preleukemia

Intervention

Biological:
• rivogenlecleucel
T cells transduced with iCasp safety switch

Drug:
• Rimiducid
administered to treat GVHD

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bellicum Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Number of adverse events after study drug (BPX-501 and/or rimiducid) administration as a measure of safety	30 days after last dose of study drug (BPX-501 and/or rimiducid)