Peritransplant Cyclosporine in Treating Patients With Hematologic Malignancies Undergoing T-Cell Depleted Allogeneic Stem Cell Transplant Followed By T-Cell Add-Back - Full Text View

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00079391

Purpose

RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow transplant or stem cell transplant helps stop the growth of cancer 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. Removing the T cells from the donor cells before transplant and giving cyclosporine before and after the transplant and may stop this from happening. Giving an infusion of the donor's T cells (donor lymphocyte infusion) later may help the patient's immune system see any remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect).

PURPOSE: This phase II trial is studying how well cyclosporine works in treating patients who are undergoing donor stem cell transplant followed by T-cell add-back (reinfusion) for hematologic malignancies.

Condition	Intervention	Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Myelodysplastic Syndromes	Biological: therapeutic allogeneic lymphocytes Drug: cyclophosphamide Drug: cyclosporine Drug: etoposide Drug: fludarabine phosphate Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed by T-Cell Add-Back for Hematological Malignancies-Effect of Peritransplant Cyclosporine on Chimerism

Resource links provided by NLM:

MedlinePlus related topics: Anemia Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma

Drug Information available for: Cyclophosphamide Fludarabine Etoposide Cyclosporine Fludarabine monophosphate Cyclosporin Etoposide phosphate

U.S. FDA Resources

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

Primary Outcome Measures:

Proportion of patients who develop full donor T cell chimerism by day 30 [ Designated as safety issue: No ]

Secondary Outcome Measures:

Acute and chronic graft-versus-host disease [ Designated as safety issue: No ]
Transplant-related mortality [ Designated as safety issue: No ]
Overall mortality [ Designated as safety issue: No ]
Leukemic relapse [ Designated as safety issue: No ]
CMV reactivation and disease [ Designated as safety issue: No ]
Graft failure [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	December 2003

Detailed Description:

OBJECTIVES:

Determine the effect of peritransplant cyclosporine on donor T-cell chimerism at 30 days post-transplantation in patients with hematologic malignancies undergoing T-cell depleted allogeneic stem cell transplantation followed by T-cell add-back.
Determine the risk of acute and chronic graft-vs-host disease from T-cell add-back at 60 days post-transplantation in patients treated with this regimen.
Determine the disease-free survival, relapse, transplant-related mortality, and death from all causes in patients treated with this regimen.
Determine the cytomegalovirus reactivation in patients treated with this regimen.
Intensify the preparative regimen for patients with refractory leukemia.

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 twice daily on days -7 to -4.

NOTE: *Patients with high-risk leukemias (marrow blasts > 10% on admission) receive etoposide IV over 4 hours on day -3 and cyclophosphamide IV over 1 hour on day -2.

Allogeneic stem cell transplantation: Patients undergo T-cell depleted allogeneic peripheral blood stem cell or bone marrow transplantation on day 0.
Graft-versus-host disease (GVHD) prophylaxis: Patients receive oral cyclosporine on days -6 to 21 and days 59 to 120 followed by a slow taper until day 180.
Donor lymphocyte infusion (DLI): Patients who do not develop significant GVHD receive DLI (T-cell add-back) on day 60 post-transplantation. Patients may receive DLI at any time after transplantation for leukemic relapse, overwhelming viral infection, or suspected graft rejection.

Patients are followed at least weekly up to day 120 post-transplantation, at 6 and 12 months, every 6 months for 1 year, and then annually for at least 3 years.

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 1 of the following hematologic malignancies:
- Chronic myelogenous leukemia, including any of the following:
  - In chronic phase, meeting 1 of the following criteria:
    - Under the age of 41 AND no prior treatment with imatinib mesylate
    - Failed prior treatment with imatinib mesylate
    - In accelerated phase or blast transformation
- Acute lymphoblastic leukemia, including any of the following:
  - Over 18 years of age and in first remission with the following high-risk features:
    - WBC > 100,000/mm^3
    - Karyotypes t9; 22, t4, t19, t11
    - Biphenotypic leukemia
  - Second or subsequent remission, primary induction failure, partially responding, or untreated relapse
- Acute myeloid leukemia, including any of the following:
  - In first remission [excludes M3 (t15; 17), M4 Eo (inv 16), and t (8; 21)]
  - Second or subsequent remission, primary induction failure, or resistant relapse
- Myelodysplastic syndromes, including any of the following:
  - Refractory anemia with transfusion dependence
  - Refractory anemia with excess blasts
  - Transformation to acute leukemia
  - Chronic myelomonocytic leukemia
- Myeloproliferative disorders in transformation to acute leukemia, including any of the following:
  - Myelofibrosis
  - Polycythemia vera
  - Essential thrombocythemia
- Chronic lymphocytic leukemia, meeting one of the following criteria:
  - Refractory to fludarabine and has bulky progressive disease
  - Thrombocytopenia (platelet count ≤ 100,000/mm^3) OR anemia (hemoglobin ≤ 10g/dL) not due to recent chemotherapy
- Non-Hodgkin's lymphoma (including mantle cell lymphoma), meeting the following criteria:
  - Relapsing or refractory to current chemotherapy and monoclonal antibody treatment
  - Unsuitable for autologous stem cell transplantation
Must have an HLA 6/6 identical family donor available

PATIENT CHARACTERISTICS:

Age

10 to 55

Performance status

ECOG 0-1

Life expectancy

Not specified

Hematopoietic

See Disease Characteristics

Hepatic

Bilirubin ≤ 4 mg/dL
Transaminases ≤ 3 times upper limit of normal

Renal

Creatinine ≤ 3 mg/dL

Cardiovascular

LVEF ≥ 40%

Pulmonary

DLCO ≥ 60% of predicted

Other

HIV negative
No major organ dysfunction that would preclude transplantation
No debilitating condition that would preclude intensive myeloablative therapy
No severe psychiatric illness that would preclude study compliance
Not pregnant
Negative pregnancy test

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics

Chemotherapy

See Disease Characteristics

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00079391

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:	CDR0000355413, NHLBI-04-H-0112
Study First Received:	March 8, 2004
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00079391 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloid leukemia in remission
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
childhood acute myeloblastic leukemia with maturation (M2)
childhood acute myeloblastic leukemia without maturation (M1)
childhood acute basophilic leukemia
childhood acute monocytic leukemia (M5b)
childhood acute eosinophilic leukemia
childhood acute erythroleukemia (M6)
childhood acute lymphoblastic leukemia in remission

recurrent childhood acute lymphoblastic leukemia
refractory chronic lymphocytic leukemia
childhood acute megakaryocytic leukemia (M7)
childhood acute minimally differentiated myeloid leukemia (M0)
childhood chronic myelogenous leukemia
recurrent childhood acute myeloid leukemia
childhood acute myeloid leukemia in remission
childhood acute monoblastic leukemia (M5a)
chronic idiopathic myelofibrosis
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
polycythemia vera
essential thrombocythemia
refractory anemia with excess blasts in transformation

Additional relevant MeSH terms:

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

Antifungal Agents
Therapeutic Uses
Syndrome
Dermatologic Agents
Alkylating Agents
Lymphoma
Etoposide
Immunoproliferative Disorders
Neoplasms by Histologic Type
Disease
Immune System Diseases
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Enzyme Inhibitors

ClinicalTrials.gov processed this record on November 09, 2009