Clinical trial NCT00045305: Reduced-Intensity Regimen Before Donor Bone Marrow Transplant in Treating Patients With Myelodysplastic Syndromes
Official title: A Phase II Study of Reduced Intensity Allogeneic Bone Marrow Transplant for the Treatment of Myelodysplastic Syndromes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Keywords: chronic myelomonocytic leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
refractory anemia
refractory anemia with excess blasts
refractory anemia with ringed sideroblasts
secondary myelodysplastic syndromes
atypical chronic myeloid leukemia, BCR-ABL1 negative
myelodysplastic/myeloproliferative neoplasm, unclassifiable
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Complete Response Rate
timeFrame: 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.
Secondary outcomes:
measure: Number of Patients Who Developed Disease Progression After Achieving Complete Response
timeFrame: 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.
measure: Overall Survival
timeFrame: 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.
measure: Proportion of Graft Versus Host Disease
timeFrame: 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.
measure: Time to Engraftment for Neutrophil
timeFrame: Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.
measure: Time to Engraftment for Platelet
timeFrame: Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Boston
country: United States
facility: Tufts-NEMC Cancer Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Cincinnati
country: United States
facility: Jewish Hospital Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Abramson Cancer Center at Penn Medicine
name: Selina M. Luger, MD
role: STUDY_CHAIR
References: