Haploidentical Transplantation in Patients With Acute Leukemia and Myelodysplasia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00475384
First received: May 16, 2007
Last updated: September 3, 2013
Last verified: September 2013
  Purpose

Objectives:

Primary:

  1. To establish the feasibility of delayed infusion of ex vivo anergized donor peripheral blood mononuclear cells (PBMC) after CD34 selected megadose haploidentical hematopoietic stem cell transplant (HSCT) Determine the feasibility of collecting parental allogeneic stimulator cells to induce anergy to the non-shared donor:recipient haplotype Determine the feasibility of collecting donor PBMC as a source of T cells for ex vivo anergization Determine the number of transplanted individuals who meet the criteria for proceeding to delayed infusion of ex vivo anergized donor PBMC
  2. To establish the safety of delayed infusion of ex vivo anergized donor PBMC by establishing the maximal number of donor T cells that can be infused without unacceptable graft-versus-host disease (GVHD)

Secondary:

  1. To evaluate in vitro the induction and specificity of alloantigen hyporesponsiveness in donor PBMC after ex vivo anergization
  2. To assess in vitro the function of immune cells engrafted in the recipient To assess in vitro whether alloantigen hyporesponsive donor T cells are present in the recipient after HSCT To develop preliminary in vitro data on the extent of pathogen-specific immunity and its rate of recovery To describe the patterns of opportunistic infections in patients so treated

Condition Intervention Phase
Acute Myelogenous Leukemia
Acute Lymphocytic Leukemia
Myelodysplastic Syndrome
Leukemia
Drug: Fludarabine
Drug: Thiotepa
Radiation: Total Body Irradiation
Drug: Melphalan
Biological: Stem Cell Transplant (SCT)
Procedure: Anergized Cell Infusion
Phase 1

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: Delayed Infusion of Ex Vivo Anergized Peripheral Blood Mononuclear Cells Following CD34 Selected Peripheral Blood Stem Cell Transplant From A Haploidentical Donor For Patients With Acute Leukemia and Myelodysplasia

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Feasibility of delayed infusion of ex vivo anergized donor PBMC after CD34 selected megadose HSCT [ Time Frame: Day 0 and Day +35 or 42+ (day of infusion of anergized cells) ] [ Designated as safety issue: Yes ]

Enrollment: 10
Study Start Date: June 2006
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Radiation+Chemotherapy+ Stem Cell Infusion
TBI (Total Body Irradiation) + Fludarabine + Thiotepa + SCT + Anergized cell infusion
Drug: Fludarabine
40 mg/m^2 By Vein Over 30 Minutes x 5 Days
Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Thiotepa
5 mg/kg By Vein Daily x 2 Days
Radiation: Total Body Irradiation
200 cGy (BID) Twice Daily Over 20-40 Minutes x 3 Days
Other Name: TBI
Biological: Stem Cell Transplant (SCT)
Infusion of normal donor stem cells on Day 0
Other Names:
  • SCT
  • Stem Cell Mobilization
Procedure: Anergized Cell Infusion
Infusion of stem cells treated with the anti-B7 antibodies on Day 35+ or 42+.
Experimental: Chemotherapy+Stem Cell Infusion
Melphalan + Thiotepa + Fludarabine + SCT + Anergized cell infusion
Drug: Fludarabine
40 mg/m^2 By Vein Over 30 Minutes x 5 Days
Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Thiotepa
5 mg/kg By Vein Daily x 2 Days
Drug: Melphalan
140 mg/m^2 by vein x 1 Day
Other Name: Alkeran
Biological: Stem Cell Transplant (SCT)
Infusion of normal donor stem cells on Day 0
Other Names:
  • SCT
  • Stem Cell Mobilization
Procedure: Anergized Cell Infusion
Infusion of stem cells treated with the anti-B7 antibodies on Day 35+ or 42+.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients </= 50 years of age meeting standard performance and end-organ function criteria for stem cell transplantation.
  2. Cardiac function: left ventricular ejection fraction > 45%
  3. Renal function: Serum creatinine < 2x upper limit of normal for age or if serum creatinine elevated beyond normal, must have creatinine clearance or glomerular filtration rate > 50% lower limit of normal for age
  4. Hepatic function: AST/ALT < 3x upper limit of normal for age and bilirubin < 2.0 mg/dl. These criteria do not apply if liver is involved with disease.
  5. Pulmonary function: Patient must have room air O2 saturation >95% and no clinical evidence of pulmonary insufficiency unless the lungs are involved with disease.
  6. Patients with acute myelogenous leukemia (AML): induction failure with < 3 induction courses, >/= second or greater complete remission (CR) (defined as <5% blasts in bone marrow and no active extramedullary disease) , CR1 with high risk features defined as history of induction failure, 5q- or monosomy 7 cytogenetic findings;
  7. Patients wih acute lymphocytic leukemia (ALL): >/= second or greater CR (defined as <5% blasts in bone marrow and no active extramedullary disease), CR1 with high risk features defined as history of induction failure or Ph+ or t(4;11) on cytogenetic analysis or any infant with MLL rearrangements on cytogenetic analysis;
  8. Patients with myelodysplastic syndrome (MDS): refractory anemia (RA) with excess blasts (EB) with intermediate (INT)-1, INT-2 or high International Prognosis Score System (IPSS) score, RAEB in transformation (iT) with INT-1, INT-2 or high IPSS score and patients with RA and INT-2 IPSS score
  9. Patients lacking a suitably matched family donor defined by genotypic or phenotypic identity for >/= 5/6 A, B, DR loci
  10. Patients lacking an immediately available genotypically matched (6/6) unrelated marrow donor or umbilical cord blood donor with suitable cell dose after a search of greater than or equal to 2 months OR patients whose medical condition is at high risk of deteriorating or whose disease is at high risk of progression during a donor search
  11. Patients must have a healthy family member donor who must be at least genotypically HLA-A, B, C, DR haploidentical to the patient.
  12. Donors must sign voluntary, written informed consent OR in the case of minor donors such consent must be signed by the parent or guardian and assent will be requested as age appropriate.
  13. Donors must be capable of undergoing leukapheresis, have adequate venous access and be willing to undergo placement of a central venous catheter should leukapheresis via peripheral access be inadequate.
  14. Note that satisfactory mobilization of donor peripheral blood stem cells (PBSC) to meet protocol criteria must take place prior to initiation of conditioning of the patient.
  15. Donors must be informed that they would be requested to undergo a second donation of PBSC or a BM harvest should the patient fail to demonstrate sustained engraftment after HSCT
  16. Donors must meet all the medical criteria for blood product donation, including negative test for HIV, freedom from other active infection, absence of medical condition posing a health risk to donation of PBSC or function of the graft.
  17. To provide a source of peripheral blood mononuclear cells to serve as allosensitizers patients must EITHER: (a) have a parent disparate with the donor for the haplotype shared by the patient and parent but not shared by the patient and donor; OR (b) be able to donate sufficient autologous cells by peripheral blood draw or unstimulated leukapheresis
  18. Female patients of child-bearing age must have a negative pregnancy test and be using an form of contraception considered effective and medically acceptable by the investigator.
  19. Voluntary written informed consent. Children will be asked for assent wherever age appropriate.

Exclusion Criteria:

  1. Active infection. Freedom from active infection is defined as: absence of an infectious diagnosis or (in patients who have had a recent positive infectious diagnosis) the resolution of fever, documentation of negative cultures or antigen testing, continuation or completion of a course of appropriate therapy, and presence of stable to resolving clinical symptoms.
  2. Evidence of HIV infection or known HIV positive serology
  3. Presence of active CNS disease
  4. ALL patients who relapse with isolated extramedullary disease after completion of treatment
  5. Any prior stem cell transplant
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00475384

Locations
United States, California
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
United States, Florida
University of Florida Shands Hospital
Gainesville, Florida, United States, 32610-0278
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Eva Guinan, M.D Dana-Farber Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00475384     History of Changes
Other Study ID Numbers: 2005-0695, NCI
Study First Received: May 16, 2007
Last Updated: September 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Acute Myelogenous Leukemia
Acute Lymphocytic Leukemia
Myelodysplastic Syndrome
Stem Cell Transplant
Haploidentical Donor
Leukemia
Fludarabine
Total Body Irradiation
Thiotepa

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia
Syndrome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Disease
Pathologic Processes
Fludarabine
Fludarabine phosphate
Melphalan
Thiotepa
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents

ClinicalTrials.gov processed this record on September 22, 2014