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

Phase 1

Withdrawn

• Conditions: Nonmalignant Neoplasm; Chronic Myeloproliferative Disorders; Leukemia; Myelodysplastic Syndromes; Lymphoma
• Interventions: Drug: cyclosporine; Drug: mycophenolate mofetil; Drug: pentostatin; Genetic: cytogenetic analysis; Genetic: fluorescence in situ hybridization; Genetic: protein analysis; Other: flow cytometry; Other: immunoenzyme technique; Other: laboratory biomarker analysis; Other: reduced-intensity transplant conditioning procedure; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation (PBSC); Radiation: total-body irradiation

• Registration Number: NCT00816413
• Lead Sponsor: University of Nebraska

Brief 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.

Detailed Description

OBJECTIVES:

Primary

* To determine the safety of pentostatin and low-dose total body irradiation followed by T-cell-reduced unrelated donor peripheral blood stem cell transplantation, in terms of regimen-related toxicity, in patients with hematological malignancies.

* To evaluate the efficacy of this regimen, measured as engraftment rate and establishment of donor hematopoietic chimerism, in these patients.

Secondary

* To determine the incidence of acute and chronic graft-versus-host disease in patients treated with this regimen.

OUTLINE:

* Reduced-intensity preparative regimen: Patients receive pentostatin IV over 30 minutes once daily on days -10 to -8 and undergo low-dose total-body irradiation on day -1.

* Unrelated donor peripheral blood stem cell transplantation (PBSCT): Patients undergo T-cell-reduced donor PBSCT on day 0.

* Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours twice daily on days -1, 0, and 1 and then orally twice daily on days 2-70 followed by a taper in the absence of GVHD. Patients also receive oral mycophenolate mofetil twice daily on days 0-27 followed by a taper.

Patients undergo bone marrow aspirate and biopsies and blood sample collection periodically for laboratory studies. Samples are analyzed for cytokines (i.e., IL-6, TNF-γ, IL-1β, and IL-10) by ELISA; phenotypic, molecular, and functional analysis of immunologic reconstitution markers (i.e., PHA, IL-2, IL-4, IL-10, IL-12, Fas, FasL, TNF, TGF-β, and IFN-γ) by flow cytometry; and cytogenetics by FISH.

After completion of study treatment, patients are followed periodically.

Study Timeline

• Study Start: 2008-09
• Study First Submitted: 2008-12-31
• Study First Submitted QC: 2008-12-31
• Study First Posted: 2009-01-01
• Primary Completion: 2010-02
• Study Completion: 2010-02
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-10
• Last Update Posted: 2023-08-14

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer	fluorescence in situ hybridization	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.
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer	total-body irradiation	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.
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer	reduced-intensity transplant conditioning procedure	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.
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer	cytogenetic analysis	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.
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer	protein analysis	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.
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer	flow cytometry	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.
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer	nonmyeloablative allogeneic hematopoietic stem cell transplantation	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.
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer	peripheral blood stem cell transplantation (PBSC)	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.
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer	immunoenzyme technique	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.
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer	laboratory biomarker analysis	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.
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer	cyclosporine	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.
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer	mycophenolate mofetil	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.
Donor Stem Cell Transplant, Pentostatin & Total-Body Irradiation for Hematological Cancer	pentostatin	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.

Primary Outcome Measures

Name	Time	Method
Stable donor engraftment	by day 70	Stable donor engraftment
Severe transplant-related toxicity	before day 100	Severe transplant-related toxicity (grade III-IV adverse events) as assessed by NCI CTCAE v2.0
Mortality	at day 100	Death

Secondary Outcome Measures

Name	Time	Method
Incidence of grade III-IV acute graft-versus-host disease	at day 100	An interim analysis will be performed after the accrual of each five patients (i.e., three interim analyses and 1 final analysis) has reached day 100.