Allogeneic Peripheral Stem Cell Transplantation Followed By Donor Lymphocyte Infusions in Treating Patients With Hematologic Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2004 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00066300
First received: August 6, 2003
Last updated: May 14, 2011
Last verified: April 2004
  Purpose

RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor are rejected by the body's normal cells. Eliminating the T cells from the donor cells before transplanting them may prevent this from happening. Infusions of donor lymphocytes may decrease the body's rejection of the transplanted peripheral stem cells.

PURPOSE: Phase II trial to study the effectiveness of allogeneic stem cell transplantation followed by donor lymphocyte infusions in treating patients who have hematologic cancer.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Biological: graft-versus-tumor induction therapy
Biological: therapeutic allogeneic lymphocytes
Drug: cyclophosphamide
Drug: cyclosporine
Drug: fludarabine phosphate
Procedure: allogeneic bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed By T Cell Add-Back For Hematological Malignancies - Effect Of Irradiated Donor Lymphocytes On Chimerism

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: May 2003
Detailed Description:

OBJECTIVES:

  • Determine the effect of irradiated donor T-cell infusion on donor T-cell chimerism 6 weeks after hematopoietic stem cell transplantation in patients with hematologic malignancies.
  • Determine the infusional toxic effects of irradiated donor lymphocytes in these patients.
  • Determine the risk of acute and chronic graft-versus-host disease from donor lymphocyte infusions on day 45 and day 100 posttransplantation in HLA 6/6 matched transplantations from a related donor in these patients.
  • Determine disease-free survival, cytomegalovirus reactivation, and relapse in patients treated with this regimen.
  • Determine transplant-related mortality and death from all causes in patients treated with this regimen.

OUTLINE:

  • Preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4 and cyclophosphamide IV over 1 hour on days -3 and -2. Patients undergo total body irradiation on days -7 to -4.
  • Pretransplantation irradiated donor lymphocyte infusion (DLI): Patients receive irradiated DLI on day -4.
  • Hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT on day 0.
  • Graft-versus-host disease prophylaxis: Patients receive oral cyclosporine on days 44-120.
  • Posttransplantation DLI: Patients receive DLI on days 45 and 100. Patients with chronic myelogenous leukemia in chronic phase who are polymerase chain reaction negative for bcr/abl receive DLI on day 45 only.

Patients are followed at 3, 6, and 12 months and then annually thereafter.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   10 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of any of the following hematologic malignancies:

    • Chronic myelogenous leukemia (CML) in chronic phase meeting 1 of the following criteria:

      • Under 41 years of age with no prior imatinib mesylate therapy
      • 10 to 55 years of age and failed prior imatinib mesylate therapy
      • 41 to 55 years of age for whom imatinib mesylate is not the treatment of choice
    • CML in accelerated phase or blast transformation
    • Acute lymphoblastic leukemia meeting any of the following criteria:

      • Over 18 years of age and in first remission with high-risk features (e.g., WBC greater than 100,000/mm^3, karyotypes t[9;22], t[4], t[19], t[11], and biphenotypic leukemia)
      • Second or subsequent remission
      • Primary induction failure
      • Partially responding or untreated relapse
    • Acute myeloid leukemia meeting any of the following criteria:

      • First remission, except with good-risk karyotypes (e.g., M3 t[15;17], M4E0 inv[16], t[8;21])
      • Second or subsequent remission
      • Primary induction failure
      • Resistant relapse
    • Myelodysplastic syndromes of any of the following types:

      • Refractory anemia (RA) with transfusion dependence
      • RA with excess blasts
      • In transformation to acute leukemia
      • Chronic myelomonocytic leukemia
    • Myeloproliferative disorders in transformation to acute leukemia, of any of the following types:

      • Myelofibrosis
      • Polycythemia vera
      • Essential thrombocythemia
    • Chronic lymphocytic leukemia that is refractory to fludarabine with 1 of the following:

      • Bulky progressive disease
      • Thrombocytopenia (WBC no greater than 100,000/mm^3)*
      • Anemia (hemoglobin no greater than 10 g/dL)* NOTE: *Not due to recent chemotherapy
    • Non-Hodgkin's lymphoma, including mantle cell lymphoma, relapsing or refractory to current chemotherapy and monoclonal antibody therapy and unsuitable for autologous stem cell transplantation
  • Availability of a HLA-identical (6/6) family donor

PATIENT CHARACTERISTICS:

Age

  • 10 to 55

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin no greater than 4 mg/dL
  • Transaminases no greater than 3 times upper limit of normal

Renal

  • Creatinine no greater than 3 mg/dL

Cardiovascular

  • LVEF at least 40% of predicted

Pulmonary

  • DLCO at least 60% of predicted

Other

  • Not pregnant
  • Negative pregnancy test
  • HIV negative
  • No severe psychiatric illness or mental deficiency that would preclude giving informed consent or complying with study treatment
  • No major illness or organ dysfunction that would preclude transplantation
  • No other prior malignancy except basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics

Chemotherapy

  • See Disease Characteristics
  • No prior continuous busulfan for more than 6 months duration

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00066300

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Study Chair: Austin J. Barrett, MD, FRCP NHLBI - Bone Marrow Transplantation Unit
  More Information

Additional Information:
No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00066300     History of Changes
Obsolete Identifiers: NCT00061581
Other Study ID Numbers: CDR0000315460, NHLBI-03-H-0192
Study First Received: August 6, 2003
Last Updated: May 14, 2011
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
primary myelofibrosis
polycythemia vera
essential thrombocythemia
adult acute lymphoblastic leukemia in remission
recurrent adult acute lymphoblastic leukemia
adult acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
refractory chronic lymphocytic leukemia
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
chronic myelomonocytic leukemia
refractory anemia
childhood acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
de novo myelodysplastic syndromes

Additional relevant MeSH terms:
Neoplasms
Myelodysplastic Syndromes
Preleukemia
Lymphoma
Leukemia
Syndrome
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 16, 2014