Clinical trial NCT00045305
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
Sponsor: Eastern Cooperative Oncology Group
Start date: 2006-10-24; Completion date: 2014-09-01
Enrollment: 17 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: 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.
Interventions: intervention 1: Cyclosporine intervention 2: Methotrexate intervention 3: Photopheresis intervention 4: Mycofenolate mofetil intervention 5: Pentostatin intervention 6: allogeneic bone marrow intervention 7: peripheral blood stem cell intervention 8: Total body irradiation
Intervention descriptions: intervention 1: Immunosuppressant intervention 2: Antimetabolite intervention 3: Psoralens intervention 4: an antibiotic with immunosuppressamt properties isolated from Penicillium spp intervention 5: Purine analogue intervention 6: Unmanipulated allogeneic bone marrow intervention 7: G-CSF mobilized peripheral blood stem cell intervention 8: a total of 600 cGy given in 3 200 cGy fractionated doses

Protocol documents: