Reduced-Intensity Regimen Before Donor Bone Marrow Transplant in Treating Patients With Myelodysplastic Syndromes

NCT ID: NCT00045305

Last Updated: 2023-06-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

17 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-10-24

Study Completion Date

2014-09-30

Brief Summary

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RATIONALE: Photopheresis treats the patient's blood with drugs and ultraviolet light outside the body and kills the white blood cells. Giving photopheresis, pentostatin, and radiation therapy before a donor bone marrow or stem cell transplant helps stop 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). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving pentostatin before transplant and cyclosporine or mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving pentostatin together with photopheresis and total-body irradiation work before donor bone marrow transplant in treating patients with myelodysplastic syndromes.

Detailed Description

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OBJECTIVES:

* Determine the complete response rate in patients with myelodysplastic syndromes treated with reduced-intensity allogeneic bone marrow transplantation, including photopheresis, total body irradiation, and pentostatin.
* Determine the disease-free and overall survival of patients treated with this regimen.
* Determine the engraftment rate of donor cells in patients treated with this regimen.
* Determine the extent and duration of acute and chronic graft-versus-host disease in patients treated with this regimen.
* Determine the toxicity of this regimen in these patients.

OUTLINE: This is a single-arm, two-stage, multicenter phase II study.

* Preparative Regimen: Patients undergo photopheresis using methoxsalen on days -7 and -6 and receive pentostatin intravenously (IV )continuously on days -5 and -4. Total body irradiation is administered on days -3 and -2 for a total of 3 doses.
* Transplantation: Allogeneic bone marrow or peripheral blood stem cells are infused on day 0.
* Acute graft-vs-host-disease (GVHD) prophylaxis: Patients receive cyclosporine IV on days -1 to 30 and then orally every 12 hours. Cyclosporine dose is then tapered beginning after day 50 and continuing for 6 months in the absence of GVHD. Once cyclosporine dose is significantly decreased, oral mycophenolate mofetil (MMF) is then administered twice a day. MMF dose is then tapered for 12 months in the absence of GVHD. Patients also receive methotrexate IV on days 1 and 3.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 33 patients would be accrued for this study within 2.1 years.

Conditions

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Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I

Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses.

Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient.

Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD.

Group Type EXPERIMENTAL

Cyclosporine

Intervention Type DRUG

Immunosuppressant

Methotrexate

Intervention Type DRUG

Antimetabolite

Photopheresis

Intervention Type DRUG

Psoralens

Mycofenolate mofetil

Intervention Type DRUG

an antibiotic with immunosuppressamt properties isolated from Penicillium spp

Pentostatin

Intervention Type DRUG

Purine analogue

allogeneic bone marrow

Intervention Type PROCEDURE

Unmanipulated allogeneic bone marrow

peripheral blood stem cell

Intervention Type PROCEDURE

G-CSF mobilized peripheral blood stem cell

Total body irradiation

Intervention Type RADIATION

a total of 600 cGy given in 3 200 cGy fractionated doses

Interventions

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Cyclosporine

Immunosuppressant

Intervention Type DRUG

Methotrexate

Antimetabolite

Intervention Type DRUG

Photopheresis

Psoralens

Intervention Type DRUG

Mycofenolate mofetil

an antibiotic with immunosuppressamt properties isolated from Penicillium spp

Intervention Type DRUG

Pentostatin

Purine analogue

Intervention Type DRUG

allogeneic bone marrow

Unmanipulated allogeneic bone marrow

Intervention Type PROCEDURE

peripheral blood stem cell

G-CSF mobilized peripheral blood stem cell

Intervention Type PROCEDURE

Total body irradiation

a total of 600 cGy given in 3 200 cGy fractionated doses

Intervention Type RADIATION

Other Intervention Names

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Sandimmune® cyclosporin A Neoral®Gengraf® Gengraf® CSA Methotrexate sodium MTX Mexate Mexate-AQ Folex Folex PFS Abitrexate Rheumatrex Amethopterin 8-methoxypsoralen Uvadex ® Methoxsalen Cellcept® RS-61443 mycophenolic acid Lilly-68618 MMF Mycophenolate mofetil DCF 2-Deoxycoformycin Nipent radiation therapy

Eligibility Criteria

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Inclusion Criteria

* One of the following cytologically proven myelodysplastic syndromes

* Refractory anemia (RA)
* RA with ringed sideroblasts
* RA with excess blasts
* Chronic myelomonocytic leukemia
* International Prognosis Scoring System (IPSS) score of at least 0.5 OR red cell transfusion dependence for at least 6 months (2 units per month)

* Patients with an IPSS score less than 0.5 may be eligible provided they previously had a higher IPSS score and received chemotherapy at that time
* Suitable human leukocyte antigen (HLA)-matched donor (related or unrelated) available

* No cord blood donors
* Related donors must be genotypically matched (HLA A, B and DR) at 5/6 or 6/6 loci and may be a sibling, parent, or child
* Unrelated donors must have high resolution typing done at A, B, C and DR, and must be matched at all or may have a single antigen or allele mismatch at no more than one of these loci
* Patients must have \< 20% blasts on bone marrow study within 1 month of study entry
* Age of 18 to 70 years
* Eastern Cooperative Oncology Group performance status 0-1
* Life expectancy at least 6 months
* At least 90 days since prior autologous bone marrow transplantation
* Serum erythropoietin level greater than 100 for patients who have not received a prior course of epoetin alfa
* No iron deficiency

* Iron deficiency anemia treated with iron replacement therapy allowed
* Bilirubin less than 2.0 mg/dL
* Alkaline phosphatase less than 2 times upper limit of normal (ULN)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 3 times ULN
* Creatinine less than 2.0 mg/dL OR creatinine clearance greater than 50 mL/min
* Left ventricular ejection fraction (LVEF) at least 45% by Multigated Acquisition scan (MUGA) or echocardiogram
* Carbon Monoxide Diffusing Capacity (DLCO) at least 50% of predicted (corrected for hemoglobin)
* Forced expiratory volume in 1 second (FEV\_1) at least 50% of predicted
* Recovered from prior chemotherapy
* Physically and psychologically capable of undergoing study regimen
* Able to receive 600 cGy of total body irradiation
* HIV negative
* Negative pregnancy test

Exclusion Criteria

* Pregnant or nursing
* Having other medical condition that would reduce life expectancy
* Active ongoing infection
* Prior myeloablative or nonmyeloablative allogeneic transplantation for Myelodysplastic syndrome or acute myeloid leukemia
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Selina M. Luger, MD

Role: STUDY_CHAIR

Abramson Cancer Center at Penn Medicine

Locations

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Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Site Status

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

Tufts-NEMC Cancer Center

Boston, Massachusetts, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Jewish Hospital Cancer Center

Cincinnati, Ohio, United States

Site Status

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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E1902

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA021115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000256928

Identifier Type: -

Identifier Source: org_study_id

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