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Donor Peripheral Stem Cell Transplant in Treating Older Patients With Hematologic Cancer

This study is ongoing, but not recruiting participants.

Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00025662
  Purpose

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and melphalan, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells that have been treated in the laboratory after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and removing the T cells from the donor cells before transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well fludarabine, melphalan, and donor peripheral stem cell transplant followed by cyclosporin work in treating older patients with hematologic cancer.


Condition Intervention Phase
Leukemia
Lymphoma
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Drug: cyclosporine
Drug: fludarabine phosphate
Drug: melphalan
Drug: therapeutic allogeneic lymphocytes
Procedure: in vitro-treated peripheral blood stem cell transplantation
Phase II

MedlinePlus related topics:   Cancer    Leukemia, Adult Acute    Leukemia, Adult Chronic    Lymphoma   

ChemIDplus related topics:   Melphalan    Fludarabine    Fludarabine monophosphate    Cyclosporine    Cyclosporin    Melphalan hydrochloride    Sarcolysin    Interleukin-2   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Open Label
Official Title:   Ex Vivo Selective Depletion of Alloreactive Donor T Lymphocytes Utilizing RFT5-SMPT-dgA, a Specific Anti-Interleukin-2 Receptor Immunotoxin: Reducing Graft-Versus-Host Disease Risk Associated With HLA-Matched, Nonmyeloablative, Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies in Older Adults

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

Primary Outcome Measures:
  • Treatment-related mortality at 100 days [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of chronic graft-vs-host disease [ Designated as safety issue: No ]
  • Long-term disease-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment:   28
Study Start Date:   May 2001

Detailed Description:

OBJECTIVES:

  • Determine the toxicity and efficacy of peripheral blood stem cell transplantation comprising selectively depleted donor T lymphocytes in older patients with hematologic malignancies.
  • Determine the incidence and severity of acute and chronic graft-versus-host disease in patients treated with this regimen.
  • Determine the engraftment kinetics and incidence of graft failure in patients treated with this regimen.
  • Determine the rates of transplant-related mortality, relapse, and disease-free and overall survival in patients treated with this regimen.

OUTLINE: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and melphalan IV on day -2. Patients undergo infusion of allogeneic T-cell-depleted and CD34-enriched peripheral blood stem cells and selectively depleted lymphocytes on day 0.

Patients also receive cyclosporine orally or IV on days -4 to 100 as graft-versus-host disease prophylaxis. Patients may receive unmanipulated or selectively depleted donor lymphocytes on day 100.

Patients are followed every 2 months for 1 year, every 3 months for 2 years, and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 15-28 patients will be accrued for this study.

  Eligibility
Ages Eligible for Study:   50 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

DISEASE CHARACTERISTICS:

  • One of the following diagnoses:

    • Chronic myelogenous leukemia in chronic or accelerated phase that has relapsed after therapy with imatinib mesylate
    • Acute lymphoblastic leukemia (ALL) in complete remission (CR) or partial remission (PR)

      • No T-cell ALL
    • Acute myelogenous leukemia (AML) in first CR or PR, including AML secondary to prior chemotherapy or prior hematologic disease (e.g., myelodysplastic syndrome [MDS] or myeloproliferative disorder) or AML in second or subsequent CR

      • No AML with good-risk karyotypes: AML M3 t(5;17), AML M4Eo (inv.16), or AML t(8;21)
    • MDS, including any of the following:

      • Refractory anemia with excess blasts (RAEB)
      • RAEB in transformation
      • MDS with poor-risk cytogenetics
      • MDS secondary to prior cytotoxic therapy or radiotherapy
      • Chronic myelomonocytic leukemia
    • Chronic lymphoblastic leukemia or prolymphocytic leukemia

      • Refractory to nucleoside analog therapy
      • Progressive bulky disease OR
      • Anemia (hemoglobin less than 10 g/dL) or thrombocytopenia (less than 100,000/mm^3) not due to recent chemotherapy
    • Mantle cell lymphoma
    • Intermediate- or high-grade non-Hodgkin's lymphoma (NHL)

      • Relapsed after autologous bone marrow transplantation (AuBMT) or peripheral blood stem cell transplantation (PBSCT) OR
      • Chemorefractory relapse
      • No T-cell NHL
    • Hodgkin's lymphoma meeting one of the following criteria:

      • Relapsed after AuBMT or PBSCT
      • Chemorefractory relapse
    • Low-grade follicular or small lymphocytic lymphoma meeting one of the following criteria:

      • Relapsed after conventional chemotherapy
      • Relapsed after AuBMT or PBSCT
      • Chemoresistant disease
  • Must have an HLA-identical family donor

    • 18 to 75 years of age NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age:

  • 50 to 75

Performance status:

  • ECOG 0-2

Life expectancy:

  • More than 3 months

Hematopoietic:

  • See Disease Characteristics
  • Absolute lymphocyte count at least 1,500/mm^3

Hepatic:

  • Bilirubin no greater than 4 mg/dL
  • Transaminases no greater than 5 times upper limit of normal

Renal:

  • Creatinine no greater than 2.5 mg/dL

Cardiovascular:

  • LVEF at least 40% of predicted

Pulmonary:

  • DLCO at least 60% of predicted

Other:

  • HIV negative
  • No other malignancy that is likely to relapse or progress within 2 years
  • No other major anticipated illness or organ failure
  • Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Disease Characteristics

Chemotherapy:

  • See Disease Characteristics

Endocrine therapy:

  • Not specified

Radiotherapy:

  • See Disease Characteristics

Surgery:

  • Not specified
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00025662

Locations
United States, Maryland
NIH - 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


Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site
 

Study ID Numbers:   CDR0000068983, NHLBI-01-H-0162, NCI-5783
First Received:   October 11, 2001
Last Updated:   July 23, 2008
ClinicalTrials.gov Identifier:   NCT00025662
Health Authority:   United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent adult Hodgkin lymphoma  
refractory chronic lymphocytic leukemia  
chronic phase chronic myelogenous leukemia  
accelerated phase chronic myelogenous leukemia  
adult acute myeloid leukemia in remission  
adult acute lymphoblastic leukemia in remission  
B-cell adult acute lymphoblastic leukemia  
non-T, non-B adult acute lymphoblastic leukemia  
refractory anemia with excess blasts  
refractory anemia with excess blasts in transformation  
chronic myelomonocytic leukemia  
recurrent grade 3 follicular lymphoma  
recurrent adult diffuse small cleaved cell lymphoma  
recurrent adult diffuse mixed cell lymphoma  
recurrent adult diffuse large cell lymphoma  
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
prolymphocytic leukemia
stage I mantle cell lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
recurrent small lymphocytic lymphoma

Study placed in the following topic categories:
Cyclosporine
Chronic myelogenous leukemia
Chronic myelomonocytic leukemia
Refractory anemia
Graft versus host disease
Miconazole
Hodgkin lymphoma, adult
Lymphoma, Mantle-Cell
Lymphoma, small cleaved-cell, diffuse
Cyclosporins
Lymphoma, large-cell, immunoblastic
Preleukemia
Leukemia, Prolymphocytic
Anemia, Refractory
Neoplasm Metastasis
Acute myeloid leukemia, adult
Hodgkin Disease
Chronic lymphocytic leukemia
Myelodysplastic syndromes
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Leukemia, B-cell, chronic
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Myeloproliferative Disorders
Acute myelogenous leukemia
Leukemia, Myeloid
Myelodysplastic myeloproliferative disease

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Disease
Immunologic Factors
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Pathologic Processes
Syndrome
Antifungal Agents
Therapeutic Uses
Antirheumatic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on September 23, 2008




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