Donor Stem Cell Transplant, Pentostatin, and Total-Body Irradiation in Treating Patients With Hematological Cancer

Summary

RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant and giving cyclosporine and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects of giving a donor stem cell transplant after pentostatin and total-body irradiation and to see how well it works in treating patients with hematological cancer.

Conditions

• Chronic Myeloproliferative Disorders
• Leukemia
• Lymphoma
• Myelodysplastic Syndromes
• Nonmalignant Neoplasm

Interventions

DRUG

cyclosporine

2 mg/kg IV over 2 hours every 12 hours starting at 0700 on days -1, 0, and +1 (total of six doses).

DRUG

mycophenolate mofetil

15 mg/kg orally twice a day starting day 0 until day +27 then stopped without tapering in the absence of aGVHD then tapered over two months in the absence of aGVHD. Doses will be rounded to the nearest 250 mg.

DRUG

pentostatin

4 mg/m2/d IV over 30 minutes daily x 3 days, (days -10, -9, -8)to begin ten days prior to stem cell infusion (Day 0).

GENETIC

cytogenetic analysis

At days +28 and +70 post-transplant, patients' blood will be evaluated for CD3 and overall WBC chimerism.

GENETIC

fluorescence in situ hybridization

Mixed chimerism is defined as the detection of 95% or less donor T cells (CD3+), expressed as a proportion of the total T cell and WBC population as measured by DNA.

GENETIC

protein analysis

Blood samples will be at baseline(day -11 or before) , days -8 and -1, prior to transplant on day 0, then weekly (days +7, +14, +21 and +28) post-transplant through day +28. Five ml's of blood will be drawn at each collection through a central line using heparinized vaccutainers. Samples will be spun down at 1200 g and plasma aspirated and stored in -80 oC until analyzed for the ELISA Assays being done for research purposes in this protocol.

OTHER

flow cytometry

Peripheral blood Peripheral blood flow cytometry for immunophenotyping including Th/c1 and Th/c2 subsets, mitogens (PHA, PWM), NK and LAK function studies, DCs, apoptosis assay of tumor cells, and lymphocyte subsets (CD4, CD8, CD19, CD56

OTHER

immunoenzyme technique

Peripheral blood for immunophenotyping including Th/c1 and Th/c2 subsets, mitogens (PHA, PWM), NK and LAK function studies, DCs, apoptosis assay of tumor cells, and lymphocyte subsets (CD4, CD8, CD19, CD56

OTHER

laboratory biomarker analysis

Donor mononuclear cells from the stem cell product (SCP) obtained with apheresis will be analyzed for surface markers, including CD3, CD4, CD8, CD19, CD14, CD56, TCR+CD8+ cells, Th/c1 and Th/c2, Fas and FasL, and DCs, as well as for apoptosis

OTHER

reduced-intensity transplant conditioning procedure

Allopurinol 300 mg orally once daily x 10 days, to begin one day prior to treatment with Pentostatin (day -11 to day -2) . Pentostatin 4 mg/m2/d IV over 30 minutes daily x 3 days, (days -10, -9, -8)to begin ten days prior to stem cell infusion (Day 0) . Pre and Post Pentostatin Hydration: 1000ml Normal Saline IV over 2 hours pre each dose of Pentostatin and 1000ml Normal Saline IV over 4 hours post each dose of Pentostatin on days -10, -9, -8. Pre Pentostatin Recommended Antiemetics: Ondansetron 32 mg IV over 30 minutes to be given 30 min. before each dose of Pentostatin on days -10, -9, -8. Alternative ondansetron equivalent or other ancillary antiemetics may be used at the discretion of the treating physician. Pred Forte Eye Drops: two drops in each eye every 4 hours while awake x 7 days after starting Pentostatin (day -10 to day -4).

PROCEDURE

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Each patient will receive up to four IV infusions administered over 30 minutes of donor T cells at increasing cell doses given at intervals.

PROCEDURE

peripheral blood stem cell transplantation (PBSC)

PBSC are infused intravenously either by infusion or IV push on day 0 through a secure intravenous access (i.e. the double-lumen central catheter place pre transplant) according to institutional guidelines.

RADIATION

total-body irradiation

2.0 GY will be administered on day -1. Total-body irradiation (TBI) will consist of 2.0 GY at 8-12cGy/min via 6MV photons delivered AP/PA fields, without lung blocks or via lateral fields with lucite compensator along the head and neck region. TLD (thermal luminescent dosimetry) will be used to verify dose uniformity. It is anticipated that TBI will be given on day -1; however, the timing of TBI administration may be altered by factors beyond the control of the Principal Investigator because of the delivery of unrelated donor stem cells.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• University of Nebraska

  lead OTHER

Principal Investigators

• Robert Bociek, MD · University of Nebraska

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

19 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-09-30

Primary Completion

2010-02-28

Completion

2010-02-28