Haploidentical Allogeneic Transplant w/Post Transplant Infusion of Regulatory T-cells (BMT Protocol 204)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Doris Duke Charitable Foundation
Information provided by (Responsible Party):
Ginna Laport, Stanford University
ClinicalTrials.gov Identifier:
NCT01050764
First received: January 11, 2010
Last updated: September 13, 2012
Last verified: September 2012
  Purpose

When a match related or matched unrelated donor is not available a Haploidentical donor (parent, sibling or child)is immediately available. The challenges associated with haploidentical HCT include increased risk of GVHD, graft rejection and impaired immune reconstitution. This trial will evaluate the safety and feasibility of simultaneous administration of conventional T cells and regulatory T cells after haploidentical allogeneic hematopoietic cell transplantation to overcome these challenges.


Condition Intervention
Leukemia
Leukemia Chronic Myelogenous Leukemia (CML)
Blood and Marrow Transplant (BMT)
Myelodysplastic Syndromes (MDS)
Lymphomas: Non-Hodgkin
Device: ClinMACS
Drug: Stem Cells

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Feasibility Trial of Post Transplant Infusion of Allogeneic Regulatory T Cells Simultaneously With Allogeneic Conventional T Cells in Patients With Hematologic Malignancies Undergoing Allogeneic Myeloablative Hematopoietic Cell Transplantation From Haploidentical Related Donors

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Determine safety and feasibility of infusing conventional T cells and regulatory T cell after HCT. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Determine maximum tolerated dose of infused regulatory and conventional T cells [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine 1 year OS and EFS, incidence and severity of GVHD; incidence of serious infections, immune reconstitution [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: June 2009
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Post Transplant Infusion arm Device: ClinMACS Drug: Stem Cells

  Eligibility

Ages Eligible for Study:   up to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:Recipient Inclusion Criteria

3.1.1 Patients with the following diseases that are histopathologically confirmed are eligible:

  1. Acute leukemia (in first remission with poor risk factors and molecular prognosis; AML with -5,-7, t(6;9), tri8, -11 and ALL with Ph+ t(9;22), t(4;22), (q34;q11)
  2. Acute leukemia with refractory disease or >CR1
  3. Chronic myelogenous leukemia (accelerated, blast or second chronic phase)
  4. Myelodysplastic syndrome (in high and high intermediate risk categories)
  5. Non-Hodgkin's lymphoma with poor risk features not suitable for autologous transplantation
  6. Refractory CLL

3.1.2 There are no limits on amount of prior therapy but there must be at least 21 days from the end of most recent prior therapy to start of transplant conditioning regimen.

3.1.3 The recipient must be <= 60 years old at time of registration.

3.1.5 Karnofsky Performance Status > 70%

3.1.6 The recipient must have a related donor genotypically HLA-A, B,C and DRB1, DQ loci haploidentical to the recipient (but differing for 2-3 HLA alleles on the unshared haplotype in the GvHD direction) and no HLA matched sibling or matched unrelated donor is identified.

3.1.7 Adequate cardiac and pulmonary function (LVEF > 45%, DLCO >50% corrected for hemoglobin)

3.1.8 Serum creatinine <1.5 mg/dL or creatinine clearance >50 ml/min for those above serum creatinine of 1.5; serum bilirubin <2.0 mg/dL; ALT <2x ULN (unless secondary to disease)

3.1.9 No prior myeloablative therapy or hematopoeitic cell transplantation

Donor Inclusion Criteria

3.3.1 Age < 70 years and weight > 25 kg. 3.3.2 Medical history and physical examination confirm good health status as defined by institutional standards 3.3.3 Seronegative for HIV Ag, hepatitis B sAg or PCR+ or hepatitis C ab or PCR+ within 30 days of apheresis collection 3.3.4 Genotypically haploidentical as determined by HLA typing 3.3.5 Female donors of child-bearing potential must have a negative serum or urine beta-HCG test within three weeks of mobilization 3.3.6 Capable of undergoing leukapheresis, have adequate venous access, and be willing to undergo insertion of a central catheter should leukapheresis via peripheral vein be inadequate 3.3.7 Capable of agreeing to second donation of PBPC (or a bone marrow harvest) should the patient fail to demonstrate sustained engraftment following the transplant 3.3.8 The donor or legal guardian greater than 18 years of age, capable of signing an IRB-approved consent form.

3.3.9 Donor Selection

The order of donor section will be as follows:

  1. If available, the recipient's biological mother will be the preferential donor
  2. If the biological mother is not available, then other available haploidentical donors will be selected based upon the presence of NK alloreactivity between donor and recipient. The donor will be selected based on the presence of NK alloreactivity as determined by high-resolution HLA typing of the C locus of both donor and recipient. Recipients lacking a KIR-ligand present in the donor along with the corresponding KIR defines "NK alloreactivity". An NK alloreactive donor will be preferentially chosen.
  3. If more than 1 NK alloreactive donor is available, then preference will be to use an NK alloreactive donor that is CMV seronegative.

Exclusion Criteria:Recipient Exclusion Criteria

3.2.1 The recipient is a suitable candidate for autologous transplantation or allogeneic transplantation with an available matched related or unrelated donor.

3.2.2 Seropositive for any of the following: HIV ab, hepatitis B sAg or PCR+ or hepatitis C ab or PCR+ 3.2.3 History of invasive Aspergillosis; presence of any other active, uncontrolled bacterial, viral or fungal infection 3.2.4 Uncontrolled CNS disease involvement 3.2.7 The recipient is a lactating female

3.4 Donor Exclusion Criteria 3.4.1 Evidence of active infection or viral hepatitis 3.4.3 Factors which place the donor at increased risk for complications from leukapheresis or G-CSF therapy 3.4.4 Lactating female 3.4.5 HIV positive

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01050764

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Ginna Laport
Doris Duke Charitable Foundation
Investigators
Principal Investigator: Ginna Laport Stanford University
  More Information

No publications provided

Responsible Party: Ginna Laport, Associate Professor of Medicine (Blood and Marrow Transplantation), Stanford University
ClinicalTrials.gov Identifier: NCT01050764     History of Changes
Other Study ID Numbers: BMT204, SU-03312009-2059, 15919
Study First Received: January 11, 2010
Last Updated: September 13, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Myelodysplastic Syndromes
Preleukemia
Chronic Disease
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Precancerous Conditions
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on April 15, 2014