Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant For Hematological Cancer

Summary

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood 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 cells 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 tacrolimus, sirolimus, antithymocyte globulin, and methotrexate before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well sirolimus, tacrolimus, and antithymocyte globulin work in preventing graft-versus-host disease in patients undergoing a donor stem cell transplant for hematological cancer .

Conditions

• Chronic Myeloproliferative Disorders
• Graft Versus Host Disease
• Infection
• Leukemia
• Lymphoma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Neoplasms
• Precancerous Condition
• Secondary Myelofibrosis
• Small Intestine Cancer

Interventions

BIOLOGICAL

anti-thymocyte globulin

0.5 mg/kg on day -3, 1.5 mg/kg on day -2 and 2.5 mg/kg on day -1 or day 0 from stem cell transplant

DRUG

cyclophosphamide

60mg/kg on days -5 and -4 from stem cell transplant

DRUG

etoposide

60mg/kg on day -4 from stem cell transplant

DRUG

fludarabine phosphate

Fludarabine 25 mg/m2/d from days -9 to -5 from stem cell transplant

DRUG

melphalan

Melphalan 140 mg/m2 on day -4 from stem cell transplant

DRUG

methotrexate

For high risk HLA-mismatch transplant only: 5 mg/m2 on days +1, +3 and +6 from stem cell transplant

DRUG

sirolimus

Adults: 12 mg loading dose on day -3 from stem cell transplant followed by 4 mg orally single morning daily dose. Pediatric Patients \<40kg: 3 mg/m2 orally on day -3 from stem cell transplant followed by 1 mg/m2 orally single morning daily dose

DRUG

tacrolimus

0.02 mg/kd/d CIV beginning on day -3 from stem cell transplant

PROCEDURE

allogeneic hematopoietic stem cell transplantation

The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight

PROCEDURE

hematopoietic stem cell transplantation

The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight

PROCEDURE

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Fludarabine 25 mg/m2/d from days -9 to -5 from stem cell transplant, Melphalan 140 mg/m2 on day -4 from stem cell transplant

PROCEDURE

peripheral blood stem cell transplantation

The target peripheral blood stem cell dose will be 5-10 x 106/kg actual body weight

RADIATION

total-body irradiation

1320 cGy in 11 fractions from day -8 to day -5 or day -9 to day -6 prior to stem cell transplant

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• City of Hope Medical Center

  lead OTHER

Principal Investigators

• Ryotaro Nakamura, MD · City of Hope Comprehensive Cancer Center

Study Design

Allocation

NON_RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

2 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-05-31

Primary Completion

2012-02-29

Completion

2012-02-29

Countries

• United States

Study Locations