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Pilot Trial of Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Hormone-Refractory Prostate Cancer


Phase 2
18 Years
75 Years
Not Enrolling
Male
Prostate Cancer

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Trial Information

Pilot Trial of Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Hormone-Refractory Prostate Cancer


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.


DISEASE CHARACTERISTICS:

- Diagnosis of adenocarcinoma of the prostate

- Metastatic and progressive disease

- Refractory to hormonal therapy

- Prostate-specific antigen (PSA) > 5 ng/mL

- Previously treated with a docetaxel-based regimen

- No CNS metastases

PATIENT CHARACTERISTICS:

Performance status

- Karnofsky 70-100%

Life expectancy

- More than 6 months

Hematopoietic

- Not specified

Hepatic

- Bilirubin < 2 times upper limit of normal (ULN)

- AST and ALT < 4 times ULN

Renal

- Creatinine clearance > 50 mL/min

Cardiovascular

- LVEF > 35%

- No symptomatic congestive heart failure

Pulmonary

- DLCO > 40% of predicted OR

- Total lung capacity or FEV_1 > 30% of predicted

Other

- HIV negative

PRIOR CONCURRENT THERAPY:

Chemotherapy

- See Disease Characteristics

Endocrine therapy

- See Disease Characteristics

PATIENT AND DONOR SELECTION CRITERIA

4.1 Patient

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.

4.2 Patient 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

4.2 Related Donor Inclusion criteria:

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.

4.3 Unrelated Donor Inclusion criteria:

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.

4.4 Related and Unrelated Donor Exclusion criteria:

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.

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Treatment-related mortality as measured by Kaplan-Meier at 5 years following transplant

Safety Issue:

No

Principal Investigator

Brandon M. Hayes-Lattin, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Oregon Health and Science University

Authority:

United States: Federal Government

Study ID:

CDR0000447211

NCT ID:

NCT00242931

Start Date:

January 2005

Completion Date:

March 2008

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • recurrent prostate cancer
  • stage IV prostate cancer
  • Prostatic Neoplasms

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