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Completed

NCT Number: NCT00045305

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

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.

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Key information

Conditions

Leukemia Anemia Anemia, Refractory Anemia, Refractory, with Excess of Blasts Bone Marrow Diseases Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Leukemia, Myeloid Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative Leukemia, Myelomonocytic, Chronic Myelodysplastic Syndromes Myelodysplastic-Myeloproliferative Diseases Myelodysplastic/Myeloproliferative Neoplasms Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Mayo Clinic Scottsdale, Scottsdale, Arizona, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

cyclosporine

Drug

Immunosuppressant

Other names: Sandimmune®, cyclosporin A, Neoral®Gengraf®, Gengraf®, CSA

methotrexate

Drug

Antimetabolite

Other names: Methotrexate sodium, MTX, Mexate, Mexate-AQ, Folex, Folex PFS, Abitrexate, Rheumatrex, Amethopterin

Photopheresis

Drug

Psoralens

Other names: 8-methoxypsoralen, Uvadex ®, Methoxsalen

Mycofenolate mofetil

Drug

an antibiotic with immunosuppressamt properties isolated from Penicillium spp

Other names: Cellcept®, RS-61443, mycophenolic acid, Lilly-68618, MMF, Mycophenolate mofetil

pentostatin

Drug

Purine analogue

Other names: DCF, 2-Deoxycoformycin, Nipent

allogeneic bone marrow

Procedure

Unmanipulated allogeneic bone marrow

peripheral blood stem cell

Procedure

G-CSF mobilized peripheral blood stem cell

Total Body Irradiation

Radiation

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

Other names: radiation therapy

Primary outcomes

  1. Complete Response Rate

    Time frame: Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

    Completed response is defined as:

    Bone marrow evaluation: Repeat bone marrow showing < 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia (see dysplasia qualifier under peripheral blood evaluation).

    Peripheral blood evaluation [absolute values must last at least 2 months] Hemoglobin >11 g/dl (untransfused, not on erythropoietin) Neutrophils (1500/mm3 (not on a myeloid growth factor)) Platelets (100,000/mm3 (not on a thrombopoetic agent)) Blasts - 0% No dysplasia. No detectable cytogenetic abnormality, if preexisting abnormality was present

Secondary outcomes

  1. Number of Patients Who Developed Disease Progression After Achieving Complete Response

    Time frame: Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

    Disease free survival (DFS) was listed as a secondary endpoint in the study protocol, which would be assessed in patients who achieved complete response (CR). It was defined to be time from CR to documented progression or to death without progression. Patients without documented progression or death reported were censored at the time of last disease evaluation. However, due to the small number of patients with CR, the number of patients who developed disease progression was reported here.

  2. Overall Survival

    Time frame: Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

    Overall survival (OS) is defined to be the time from registration to death from any cause, with follow-up censored at the date of last contact. Kaplan-Meier method was used to estimate the distribution of OS.

  3. Proportion of Graft Versus Host Disease

    Time frame: Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

    Proportion of Graft versus Host Disease is calculated as number of patients with Graft versus Host Disease divided by all eligible and treated patients

  4. Time to Engraftment for Neutrophil

    Time frame: Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.

    Time to neutrophil engraftment is defined from date of infusion to date of neutrophil engraftment. Neutrophil engraftment is defined as ANC > 500/mm3 on two consecutive measurements. The date of engraftment is the date of the first ANC > 500/mm3.

  5. Time to Engraftment for Platelet

    Time frame: Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.

    Time to platelet engraftment is defined from date of infusion to date of platelet engraftment. The platelet engraftment is defined as platelets > 20,000 on two consecutive measurements, at least seven days apart, without platelet transfusions in between and for at least three days before the first measurement that is over 20,000. The date of engraftment is the date of the first measurement that is over 20,000.

Sponsors and collaborators

Lead sponsor

Eastern Cooperative Oncology Group

Network

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study title

A Phase II Study of Reduced Intensity Allogeneic Bone Marrow Transplant for the Treatment of Myelodysplastic Syndromes

Important dates

Study start
2006
Primary completion
2014
Study completion
2014
First posted
Jan 27, 2003
Registry last updated
Jun 28, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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