Reduced-Intensity Regimen Before Donor Bone Marrow Transplant in Treating Patients With Myelodysplastic Syndromes
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00045305|
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : January 19, 2015
Last Update Posted : January 19, 2015
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.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms||Drug: Cyclosporine Drug: Methotrexate Drug: Photopheresis Drug: Mycofenolate mofetil Drug: Pentostatin Procedure: allogeneic bone marrow Procedure: peripheral blood stem cell Radiation: Total body irradiation||Phase 2|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||17 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Reduced Intensity Allogeneic Bone Marrow Transplant for the Treatment of Myelodysplastic Syndromes|
|Study Start Date :||May 2005|
|Actual Primary Completion Date :||February 2014|
|Actual Study Completion Date :||September 2014|
Experimental: 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.
Drug: Mycofenolate mofetil
an antibiotic with immunosuppressamt properties isolated from Penicillium spp
Procedure: allogeneic bone marrow
Unmanipulated allogeneic bone marrow
Procedure: peripheral blood stem cell
G-CSF mobilized peripheral blood stem cell
Radiation: Total body irradiation
a total of 600 cGy given in 3 200 cGy fractionated doses
Other Name: radiation therapy
- 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
- 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.
- 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.
- 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
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00045305
|United States, Arizona|
|Mayo Clinic Scottsdale|
|Scottsdale, Arizona, United States, 85259-5499|
|United States, Florida|
|Mayo Clinic - Jacksonville|
|Jacksonville, Florida, United States, 32224|
|United States, Massachusetts|
|Tufts-NEMC Cancer Center|
|Boston, Massachusetts, United States, 02111|
|United States, Minnesota|
|Mayo Clinic Cancer Center|
|Rochester, Minnesota, United States, 55905|
|United States, Ohio|
|Jewish Hospital Cancer Center|
|Cincinnati, Ohio, United States, 45236|
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104-4283|
|Study Chair:||Selina M. Luger, MD||Abramson Cancer Center of the University of Pennsylvania|