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Trial record 14 of 16 for:    "Adult Acute Lymphocytic Leukemia" | "Thiotepa"

Laboratory-Treated Lymphocyte Infusion After Haploidentical Donor Stem Cell Transplant

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ClinicalTrials.gov Identifier: NCT00376480
Recruitment Status : Completed
First Posted : September 15, 2006
Last Update Posted : July 3, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Eva C. Guinan, MD, Dana-Farber Cancer Institute

Brief Summary:

RATIONALE: Giving total-body irradiation and chemotherapy, such as thiotepa and fludarabine, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methylprednisolone and antithymocyte globulin before transplant and peripheral blood cells that have been treated in the laboratory after transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated peripheral blood cell infusion after donor stem cell transplant in treating patients with hematologic cancers or other diseases.


Condition or disease Intervention/treatment Phase
Leukemia Myelodysplastic Syndromes Biological: anti-thymocyte globulin Biological: peripheral blood lymphocyte therapy Drug: fludarabine phosphate Drug: methylprednisolone Drug: thiotepa Procedure: allogeneic hematopoietic stem cell transplantation Procedure: in vitro-treated peripheral blood stem cell transplantation Radiation: total-body irradiation Phase 1

Detailed Description:

OBJECTIVES:

Primary

  • Establish the feasibility of delayed infusion of ex vivo anergized donor peripheral blood mononuclear cells (PBMC) after CD34 (cluster designation 34)-selected megadose haploidentical hematopoietic stem cell transplantation (HSCT) in patients with hematopoietic cancers or other diseases.
  • Determine the feasibility of collecting parental allogeneic stimulator cells to induce anergy to the nonshared donor-recipient haplotype in these patients.
  • 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.
  • Establish the safety of delayed infusion of ex vivo anergized donor PBMC by establishing the maximum number of donor T cells that can be infused without unacceptable graft-versus-host disease.

Secondary

  • Evaluate, in vitro, the induction and specificity of alloantigen hyporesponsiveness in donor PBMC after ex vivo anergization.
  • Assess, in vitro, the function of immune cells engrafted in these patients.
  • Assess, in vitro, whether alloantigen hyporesponsive donor T cells are present in these patients.
  • Develop, preliminarily, in vitro data on the extent of pathogen-specific immunity and its rate of recovery.
  • Describe the patterns of opportunistic infections in these patients.

OUTLINE: This is a multicenter, dose-escalation study of ex vivo anergized allogeneic peripheral blood mononuclear cells (PBMC). Patients who are treated on any dose level except dose level 1 are stratified according to age (under 17 [pediatric] vs 17 and over [adult]).

  • Myeloablative conditioning regimen: Patients undergo total-body irradiation twice daily on days -11 to -9. Patients also receive thiotepa IV over 4 hours on days -8 and -7, fludarabine phosphate IV over 30 minutes on days -7 to -3, and anti-thymocyte globulin IV over 8 hours and methylprednisolone IV over 15-30 minutes on days -6 to -3.
  • Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo CD34-selected PBSCT on day 0.
  • Ex vivo anergized allogeneic PBMC infusion: If cells have engrafted and patients are free of active uncontrolled infection and graft-vs-host disease, patients undergo allogeneic or autologous PBMC infusion on day 35 or 42.

Cohorts of 3-8 patients receive escalating doses of ex vivo anergized allogeneic PBMCs until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 5 or 3 of 8 patients experience dose-limiting toxicity.

After completion of study, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Delayed Infusion of Ex Vivo Anergized Peripheral Blood Mononuclear Cells Following CD34 Selected Peripheral Blood Stem Cell Transplantation From a Haploidentical Donor for Patients With Acute Leukemia and Myelodysplasia
Actual Study Start Date : June 2005
Actual Primary Completion Date : June 2010
Actual Study Completion Date : May 16, 2018


Arm Intervention/treatment
Experimental: administration of adoptive donor lymphocyte infusion
administration of donor lymphocytes made using costimulatory blockade ex vivo
Biological: anti-thymocyte globulin
Biological: peripheral blood lymphocyte therapy
Drug: fludarabine phosphate
Drug: methylprednisolone
Drug: thiotepa
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: in vitro-treated peripheral blood stem cell transplantation
Radiation: total-body irradiation



Primary Outcome Measures :
  1. Feasibility of making and administering the adoptive T cell product [ Time Frame: from conditioning through administration of anergized cells on day 35-42 ]
    ability to collect sufficient cells, make anergized product with good viability, without contamination and infuse per study toxicity of the conditioning regimen, the likelihood of engraftment, and the subsequent percentage of individuals who would be eligible to receive aDLI were determined.

  2. Safety of administering the adoptive T cell product on day 35-42 post haploidentical transplant [ Time Frame: the period from aDLI infusion through D100 ]
    rates of graft failure with CD34 selected product, adverse and severe adverse reactions attributable to infusion of anergized donor cells, including fever, hypotension, acute graft vs host disease, organ dysfunction

  3. Alloreactivity engendered by administering the adoptive T cell product [ Time Frame: from cell infusion through day 100 ]
    occurrence and severity of acute GVHD


Secondary Outcome Measures :
  1. Efficacy in restoring adaptive immunity [ Time Frame: from aDLI thorough 1 year ]
    incidence of viral infection and type of immune reconstitution by phenotype and function of T cells



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:

    • Acute lymphocytic leukemia

      • In ≥ second complete remission (CR), defined as < 5% blasts in bone marrow (BM) and no active extramedullary disease OR in first CR with any of the following high risk features:

        • History of induction failure
        • Philadelphia chromosome positive
        • t(4;11) by cytogenetic analysis
        • Any infant with MLL rearrangements on cytogenetic analysis
      • No relapse with isolated extramedullary disease after completion of prior treatment
    • Acute myeloid leukemia

      • Failed induction therapy after < 3 courses
      • In ≥ second CR, defined as < 5% blasts in BM and no active extramedullary disease OR in first CR with any of the following high-risk features:

        • History of induction failure = 5q- or monosomy 7 cytogenetic findings
    • Any of the following myelodysplastic syndromes:

      • Refractory anemia (RA) with excess blasts (RAEB) with a high International Prognostic Scoring System (IPSS) score or score of intermediate-1(INT-1) or intermediate-2 (INT-2)
      • RAEB in transformation with INT-1, INT-2, or high IPSS score
      • RA with INT-2 score
  • Patients must have a healthy, related donor who is at least genotypically HLA-A, B, C, and DR haploidentical to the patient

    • No suitably matched family donor defined by genotypic or phenotypic identity for ≥ 5/6 A, B, or DR loci
    • No immediately available genotypically matched (6/6) unrelated marrow donor
    • No immediately available umbilical cord blood donor with suitable cell dose after a search ≥ 2 months
    • Patients whose medical condition is at high risk of deteriorating or whose disease is at high risk of progression during a donor search are eligible
  • Has a parent with a haplotype that is disparate from that of the donor for the haplotype shared by the patient and parent, but not shared by the patient and donor OR patient is able to donate sufficient autologous cells by peripheral blood draw or unstimulated leukapheresis
  • No active CNS disease

PATIENT CHARACTERISTICS:

  • Room air O_2 saturation > 95% unless the lungs are involved with disease
  • No clinical evidence of pulmonary insufficiency unless the lungs are involved with disease
  • AST and ALT < 3 times upper limit of normal (ULN)*
  • Bilirubin < 2.0 mg/dL*
  • Creatinine < 2 times ULN OR creatinine clearance or glomerular filtration rate > 50% of the lower limit of normal
  • LVEF > 45% OR shortening fraction > 20%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active infection, 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
  • No evidence of HIV infection OR known HIV positivity NOTE: *Does not apply if liver is involved with disease

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior stem cell transplantation
  • No other concurrent immunosuppressive therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00376480


Locations
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United States, California
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
United States, Florida
University of Florida Health Science Center - Gainesville
Gainesville, Florida, United States, 32610
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Study Chair: Eva Guinan, MD Dana-Farber Cancer Institute

Publications of Results:
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Responsible Party: Eva C. Guinan, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00376480     History of Changes
Obsolete Identifiers: NCT00475384
Other Study ID Numbers: 05-030
P01CA100265 ( U.S. NIH Grant/Contract )
P30CA006516 ( U.S. NIH Grant/Contract )
MDA-2005-0695
First Posted: September 15, 2006    Key Record Dates
Last Update Posted: July 3, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Eva C. Guinan, MD, Dana-Farber Cancer Institute:
adult acute lymphoblastic leukemia in remission
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
refractory anemia
adult acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary acute myeloid leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
secondary myelodysplastic syndromes
childhood myelodysplastic syndromes
Additional relevant MeSH terms:
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Thiotepa
Leukemia
Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Methylprednisolone
Fludarabine
Fludarabine phosphate
Antilymphocyte Serum
Antineoplastic Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antimetabolites, Antineoplastic
Antimetabolites