Flu/TBI in Treating Patients Not Responding to Previous Hormone Therapy

NCT ID: NCT00242931

Last Updated: 2012-06-01

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2008-03-31

Brief Summary

RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor stem cell transplant helps stop the growth of cancer cells. It also stops 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 cyclosporine and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving fludarabine together with total-body irradiation works in treating patients who are undergoing a donor stem cell transplant for progressive metastatic prostate cancer that has not responded to previous hormone therapy.

Detailed Description

OBJECTIVES:

• Determine the treatment-related mortality in patients with hormone-refractory, progressive metastatic prostate cancer treated with nonmyeloablative conditioning comprising fludarabine and total-body irradiation followed by allogeneic hematopoietic stem cell transplantation.

OUTLINE:

• Nonmyeloablative conditioning regimen: Patients receive fludarabine IV on days -4 to -2 and total-body irradiation (TBI) on day 0.
• Allogeneic hematopoietic stem cell transplantation (AHSCT): After TBI, patients undergo AHSCT on day 0.
• Immunosuppression: Patients receive oral cyclosporine twice daily on days -3 to 56 followed by a taper until day 81. Patients also receive oral mycophenolate mofetil twice daily on days 0-27 (if patient has a related donor) OR three times daily on days 0-29 and then twice daily on days 30-149 followed by additional tapering until day 180 (if patient has an unrelated donor).

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fludarabine, TBI, Cyclosporine, MMF

Fludarabine 30 mg/m2/day x 3, day -4 to day -2 TBI 200 cGy x 1, day 0 For related donors: cyclosporine (CSP) 5 mg/kg p.o. bid, day -3 to day +56, then taper by 20% every 5 days to be completed by day +81 For related donors: mycophenolate mofetil (MMF) 15 mg/kg p.o. q 12 hours, day 0 to day +27, then stop

For unrelated donors: cyclosporine (CSP) 5 mg/kg p.o. bid, day -3 to day +56, then taper by 20% every 5 days to be completed by day +81 For unrelated donors: mycophenolate mofetil (MMF) 15 mg/kg tid day +0 to day +29, 15 mg/kg bid day +30 to day +149, and then taper by 25% per week from day +150 to day +180. Discontinue by day +181.

Group Type: EXPERIMENTAL

Nonmyeloablative stem cell conditioning regimen

Intervention Type: OTHER

Conditioning:

Fludarabine 30 mg/m2/day x 3, day -4 to day -2 TBI 200 cGy x 1, day 0

Hematopoeitic Stem Cell Transplantation:

Infusion of peripheral blood stem cells, day 0

Immunosuppression:

For related donors: cyclosporine (CSP) 5 mg/kg p.o. bid, day -3 to day +56, then taper by 20% every 5 days to be completed by day +81 For related donors: mycophenolate mofetil (MMF) 15 mg/kg p.o. q 12 hours, day 0 to day +27, then stop

For unrelated donors: cyclosporine (CSP) 5 mg/kg p.o. bid, day -3 to day +56, then taper by 20% every 5 days to be completed by day +81 For unrelated donors: mycophenolate mofetil (MMF) 15 mg/kg tid day +0 to day +29, 15 mg/kg bid day +30 to day +149, and then taper by 25% per week from day +150 to day +180. Discontinue by day +181.

Interventions

Nonmyeloablative stem cell conditioning regimen

Conditioning:

Fludarabine 30 mg/m2/day x 3, day -4 to day -2 TBI 200 cGy x 1, day 0

Hematopoeitic Stem Cell Transplantation:

Infusion of peripheral blood stem cells, day 0

Immunosuppression:

For related donors: cyclosporine (CSP) 5 mg/kg p.o. bid, day -3 to day +56, then taper by 20% every 5 days to be completed by day +81 For related donors: mycophenolate mofetil (MMF) 15 mg/kg p.o. q 12 hours, day 0 to day +27, then stop

For unrelated donors: cyclosporine (CSP) 5 mg/kg p.o. bid, day -3 to day +56, then taper by 20% every 5 days to be completed by day +81 For unrelated donors: mycophenolate mofetil (MMF) 15 mg/kg tid day +0 to day +29, 15 mg/kg bid day +30 to day +149, and then taper by 25% per week from day +150 to day +180. Discontinue by day +181.

Intervention Type: OTHER

Other Intervention Names

Mini Transplant

Eligibility Criteria

Inclusion Criteria

4.1.1 Males aged 18-75.

4.1.2 Pathologically proven adenocarcinoma of the prostate with metastases and progressive disease (new metastatic lesions or increase in cancer-related pain or a rising PSA defined by consensus criteria. (A rising PSA will be defined as 2 measurements higher than an initial value. The second of the 3 measurements must be at least 7 days after the first).

4.1.3 Progressive disease despite hormonal management (including antiandrogen withdrawal, 6 weeks for bicalutamide, 4 weeks for flutamide or nilutamide)

4.1.4 PSA > 5 ng/mL

4.1.5 Serum testosterone level < 50 ng/mL

4.1.6 Prior treatment with a docetaxel-based regimen.

4.1.7 Performance status: Karnofsky Performance Scale (KPS) 70-100%. (Appendix III).

4.1.8 Signed informed patient consent.

4.3.1 Age 18-75

4.3.2 Related to the patient and genotypically or phenotypically HLA-identical. (Appendix IV)

4.3.3 Able to give consent to peripheral blood stem cell mobilization with G-CSF and apheresis collection. Bone marrow donors are not eligible.

4.4.1 Age 18-75.

4.4.2 Unrelated donors who are prospectively:

4.4.2.1 Matched for HLA-DRB1 and -DQB1 alleles by high resolution typing AND 4.4.2.2 Matched for all serologically recognized HLA-A or -B or -C antigens and at least five of six HLA-A or -B or -C alleles as defined by Appendix IV.

4.4.3 Able to give consent to peripheral blood stem cell mobilization with G-CSF and apheresis collection. Bone marrow unrelated donors are not eligible.

Exclusion Criteria

4.2.1 Expected survival less than 6 months

4.2.2 Active central nervous system involvement or spinal instability

4.2.3 Organ dysfunction:

4.2.3.1 Cardiac: Ejection fraction <35% or symptomatic congestive heart failure.

4.2.3.2 Pulmonary: DLCO <40% of predicted or either TLC or FEV1 < 30% predicted.

4.2.3.3 Liver dysfunction: serum total bilirubin >2x upper limit of normal (ULN) or either ALT or AST >4x ULN

4.2.3.4 Renal dysfunction: creatinine clearance < 50 ml/min

4.2.4 HIV seropositivity

4.5.1 Identical twin.

4.5.2 Any contraindication to the administration of G-CSF for mobilization.

4.5.3 Serious medical or psychological illness.

4.5.4 Prior malignancy within the preceding five years, with the exception of non-melanoma skin cancers.

4.5.5 HIV seropositivity.

4.5.6 The donor is pregnant, has a positive serum ßhCG or is lactating.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

OHSU Knight Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brandon M. Hayes-Lattin, MD

Role: STUDY_CHAIR

Oregon Health and Science University

Other Identifiers

OHSU-SOL-04109-L

Identifier Type: OTHER

Identifier Source: secondary_id

OHSU-373

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000447211

Identifier Type: -

Identifier Source: org_study_id