Donor Peripheral Stem Cell Transplant in Treating Older Patients With Hematologic Cancer - Full Text View

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	Biological: therapeutic allogeneic lymphocytes Drug: cyclosporine Drug: fludarabine phosphate Drug: melphalan Procedure: in vitro-treated peripheral blood stem cell transplantation	Phase II

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

Resource links provided by NLM:

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

Drug Information available for: Fludarabine Cyclosporine Fludarabine monophosphate Cyclosporin Melphalan

U.S. FDA Resources

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

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Study Chair:

Austin J. Barrett, MD, FRCP

NHLBI - Bone Marrow Transplantation Unit

More Information

Additional Information:

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

No publications provided

Study ID Numbers:	CDR0000068983, NHLBI-01-H-0162, NCI-5783
Study First Received:	October 11, 2001
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00025662 History of Changes
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:

Anti-Infective Agents
Chronic Myelomonocytic Leukemia
Cyclosporine
Lymphoma, Mantle-Cell
Mantle Cell Lymphoma
Cyclosporins
Follicular Lymphoma
Refractory Anemia
Graft Versus Host Disease
Preleukemia
Acute Myelocytic Leukemia
Leukemia, Prolymphocytic
Anemia, Refractory
Acute Myeloid Leukemia, Adult
Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasm Metastasis
Hodgkin Disease
Myelodysplastic Myeloproliferative Disease
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Myeloproliferative Disorders
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Fludarabine
Chronic Myelogenous Leukemia
Lymphoma, Non-Hodgkin

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Cyclosporine
Immunologic Factors
Precancerous Conditions
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Cyclosporins
Leukemia
Preleukemia
Pathologic Processes
Therapeutic Uses
Antifungal Agents

Syndrome
Dermatologic Agents
Lymphoma
Neoplasms by Histologic Type
Immunoproliferative Disorders
Disease
Immune System Diseases
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Enzyme Inhibitors
Fludarabine monophosphate
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases

ClinicalTrials.gov processed this record on September 02, 2009