Haploidentical Allogeneic Transplant With Post-transplant Infusion of Regulatory T-cells

NCT01050764 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: IRB-15919BMT204SU-03312009-2059
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with hematologic malignancies will receive myeloablative chemotherapy followed by stem cell rescue with bone marrow or hematopoietic peripheral blood stem cells collected by apheresis from a filgrastim- (G-CSF)-mobilized haploidentical related-donor, ie, hematopoietic peripheral blood stem cell transplant (HSCT).

Conditions

Leukemia, Acute; Chronic Myelogenous Leukemia (CML); Myelodysplastic Syndrome (MDS); Non-Hodgkin Lymphoma (NHL); Chronic Lymphocytic Leukemia (CLL); Acute Myelogenous Leukemia (AML); Acute Lymphoblastic Leukemia (ALL)

Outcome Measures

Primary Outcomes (1)

• Maximum-tolerated Dose (MTD) of Regulatory and Conventional T-cells

  The maximum-tolerated dose (MTD) was to be determined based on the safety and feasibility observed for a pre-determined set of cellular dose level combinations of regulatory T-cells (T-reg) and conventional T-cells (T-con).

  30 days after HSCT infusion

Secondary Outcomes (5)

• Acute Graft-versus-Host-Disease (aGvHD)

  1 year

• Overall Survival (OS), 1 Year

  1 year

• Median Overall Survival (OS)

  25 months

• To Measure the Incidence and Severity of Acute and Chronic GvHD

  1 year

• Serious Infections

  1 year

Study Arms (1)

T-reg Cell Infusion after Allogeneic Stem Cell Transplant

EXPERIMENTAL

Drug: Regulatory T-cells; Drug: Conventional T-cells; Drug: Melphalan; Drug: Thiotepa; Device: Fludarabine; Drug: Anti-thymocyte globulin, rabbit; Drug: CliniMACS CD34 Reagent System

Interventions

Regulatory T-cells DRUG

To ameliorate the impaired immune recovery and address the significant relapse incidence in the haploidentical setting. Cells will be selected by a tandem selection process and infused on day +14. These are the enriched but naturally-occurring regulatory T cells. Possible dose cohorts and levels are: Cohort 1 * T-reg: 1 x 10e5/kg * T-con: 3 x10e5/kg Cohort 2 * T-reg: 3 x 10e5/kg * T-con: 1 x 10e6/kg Cohort 3 * T-reg: 1 x 10e6/kg * T-con: 3 x 10e6/kg Cohort 4 * T-reg: 3 x 10e6/kg * T-con: 1 x 10e7/kg

Also known as: T-reg cells

T-reg Cell Infusion after Allogeneic Stem Cell Transplant

Conventional T-cells DRUG

These are conventional (unselected) donor T-cells. Cell dosage of the infusion will be based on the CD3+ cell content and infused on day +16.

Also known as: T-con cells

T-reg Cell Infusion after Allogeneic Stem Cell Transplant

Melphalan DRUG

Anti-cancer chemotherapy drug administered IV at 140 mg/m² on Day -8 prior to HSCT (a component of the conditioning regiment prior to infusion of cells)

Also known as: L-PAM, L-Sarcolysin, Phenylalanine Mustard

T-reg Cell Infusion after Allogeneic Stem Cell Transplant

Thiotepa DRUG

Anti-cancer chemotherapy drug administered IV at 10 mg/kg on Day -7 prior to HSCT (a component of the conditioning regiment prior to infusion of cells)

Also known as: thiophosphamide, TESPA, TSPA

T-reg Cell Infusion after Allogeneic Stem Cell Transplant

Fludarabine DEVICE

Anti-cancer chemotherapy drug administered IV at 160mg/m² on Days -6; -5; -4; and -3 prior to HSCT (a component of the conditioning regiment prior to infusion of cells

Also known as: Fludarabine phosphate, Fludarabine 5'-monophosphate, FAMP, Fludara

T-reg Cell Infusion after Allogeneic Stem Cell Transplant

Anti-thymocyte globulin, rabbit DRUG

Rabbit-derived antibodies against human T-cells used as transplant rejection prophylaxis. Administered at 6 mg/kg IV on Days -6; -5; -4; and -3 prior to HSCT

Also known as: Thymoglobulin, rATG

T-reg Cell Infusion after Allogeneic Stem Cell Transplant

CliniMACS CD34 Reagent System DRUG

An in vitro medical device system that uses antibodies conjugated to magnetic beads to select and enrich for CD34+ blood stem cells from the allogeneic donor apheresis product prior to HSCT, while removing other cells that can cause GvHD. CD34+ cell dosage will be based on the participant's body weight.

T-reg Cell Infusion after Allogeneic Stem Cell Transplant

Eligibility Criteria

• Age: Up to 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• RECIPIENT
• Histopathologically-confirmed:
• Acute leukemia (in first remission with poor risk factors and molecular prognosis)
• Acute myelogenous leukemia (AML) with -5,-7, t (6;9), tri8, -11
• Acute lymphoblastic leukemia (ALL) with Ph+ t (9;22), t (4;22), (q34;q11)
• Acute leukemia with refractory disease or \> Complete Remission (CR) 1
• Chronic myelogenous leukemia (CML) (accelerated, blast or second chronic phase)
• Myelodysplastic syndrome (in high and high intermediate risk categories)
• Non-Hodgkin's lymphoma (NHL) with poor risk features and not suitable for autologous transplantation
• Refractory Chronic lymphocytic leukemia (CLL)
• At least 21 days from the end of most recent prior therapy to start of the transplant conditioning regimen
• Must be \< 60 years old at time of registration.
• Karnofsky Performance Status (KPS) \> 70%
• Must have related donor who is:
• Genotypically human leukocyte antigen (HLA) -A, B,C and DR beta 1 (DRB1), DQ loci haploidentical to the recipient (but differing for 2 to 3 HLA alleles on the unshared haplotype in the graft-versus-host disease (GvHD) direction)

You may not qualify if:

• RECIPIENT:
• Suitable candidate for autologous transplantation or allogeneic transplantation with an available matched-related or matched-unrelated donor
• Seropositive for:
• HIV ab
• Hepatitis B sAg or PCR+
• Hepatitis C ab or PCR+
• History of invasive Aspergillosis
• Any active, uncontrolled bacterial, viral or fungal infection
• Uncontrolled central nervous system (CNS) disease involvement
• Lactating female
• DONOR:
• Evidence of active infection or viral hepatitis
• Factors of increased risk for complications from leukapheresis or granulocyte-colony stimulating factor (G-CSF) therapy
• Lactating female
• HIV-positive

Sponsors & Collaborators

• Everett Meyer: lead
• Doris Duke Charitable Foundation: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Melphalan; Thiotepa; Antilymphocyte Serum; thymoglobulin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Everett H Meyer, MD, PhD; Assistant Professor of Medicine
• Organization: Stanford University Medical Center

evmeyer@stanford.edu

650-725-5816

Study Officials

• Everett H Meyer, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine (Blood and Marrow Transplantation)

Study Record Dates

• First Submitted: January 11, 2010
• First Posted: January 15, 2010
• Study Start: June 1, 2009
• Primary Completion: August 1, 2012
• Study Completion: June 1, 2014
• Last Updated: June 27, 2018
• Results First Posted: May 11, 2017

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)