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

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

Sponsors

Lead Sponsor: Eastern Cooperative Oncology Group

Collaborator: National Cancer Institute (NCI)

Source Eastern Cooperative Oncology 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.

Overall Status Completed
Start Date May 2005
Completion Date September 2014
Primary Completion Date February 2014
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Complete Response Rate 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 Outcome
Measure Time Frame
Number of Patients Who Developed Disease Progression After Achieving Complete Response 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 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 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.
Time to Engraftment for Neutrophil 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 Engraftment for Platelet Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.
Enrollment 17
Condition
Intervention

Intervention Type: Drug

Intervention Name: Cyclosporine

Description: Immunosuppressant

Arm Group Label: Arm I

Intervention Type: Drug

Intervention Name: Methotrexate

Description: Antimetabolite

Arm Group Label: Arm I

Intervention Type: Drug

Intervention Name: Photopheresis

Description: Psoralens

Arm Group Label: Arm I

Intervention Type: Drug

Intervention Name: Mycofenolate mofetil

Description: an antibiotic with immunosuppressamt properties isolated from Penicillium spp

Arm Group Label: Arm I

Intervention Type: Drug

Intervention Name: Pentostatin

Description: Purine analogue

Arm Group Label: Arm I

Intervention Type: Procedure

Intervention Name: allogeneic bone marrow

Description: Unmanipulated allogeneic bone marrow

Arm Group Label: Arm I

Intervention Type: Procedure

Intervention Name: peripheral blood stem cell

Description: G-CSF mobilized peripheral blood stem cell

Arm Group Label: Arm I

Intervention Type: Radiation

Intervention Name: Total body irradiation

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

Arm Group Label: Arm I

Other Name: radiation therapy

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

Gender: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Selina M. Luger, MD Study Chair Abramson Cancer Center of the University of Pennsylvania
Location
Facility:
Mayo Clinic Scottsdale | Scottsdale, Arizona, 85259-5499, United States
Mayo Clinic - Jacksonville | Jacksonville, Florida, 32224, United States
Tufts-NEMC Cancer Center | Boston, Massachusetts, 02111, United States
Mayo Clinic Cancer Center | Rochester, Minnesota, 55905, United States
Jewish Hospital Cancer Center | Cincinnati, Ohio, 45236, United States
Abramson Cancer Center of the University of Pennsylvania | Philadelphia, Pennsylvania, 19104-4283, United States
Location Countries

United States

Verification Date

January 2015

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Arm I

Type: Experimental

Description: 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.

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov