Sirolimus, Tacrolimus, Thymoglobulin and Rituximab as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Haploidentical and HLA Partially Matched Donor Hematopoietic Cell Transplantation

Summary

This Phase II clinical trial was designed for patients with hematologic malignancies in need of donor peripheral blood stem cell transplant, and have no HLA matched donor. Therefore It will test the efficacy of combining sirolimus, tacrolimus, antithymocyte globulin, and rituximab in preventing graft versus host disease in transplants from HLA Haploidentical and partially mismatched donors.

Conditions

• Chronic Myeloproliferative Disorders
• Graft Versus Host Disease
• Leukemia
• Lymphoma
• Lymphoproliferative Disorder
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Neoplasms

Interventions

BIOLOGICAL

anti-thymocyte globulin

Infuse the first dose over a minimum of 6 hours, and subsequent doses over a minimum of 4 hours via a 0.22 micron in-line filter.

BIOLOGICAL

rituximab

The total dose chosen for this protocol is 28 mg/kg divided in two doses (14 mg/kg on days -7 and +3). Initial infusion: Start rate of 50 mg/hour; if there is no reaction, increase the rate by 50 mg/hour increments every 30 minutes, to a maximum rate of 400 mg/hour. Subsequent infusions: If patient did not tolerate initial infusion follow initial infusion guidelines. If patient tolerated initial infusion, start at 100 mg/hour; if there is no reaction, increase the rate by 100 mg/hour increments every 30 minutes, to a maximum rate of 400 mg/hour. Note: If a reaction occurs, slow or stop the infusion. If the reaction abates, restart infusion at 50% of the previous rate. In patients who tolerated the Rituximab well in the past, a rapid infusion rate can be used over 90 minutes with 20% of the dose administered in the first 30 minutes and the remaining 80% is given over 60 minutes.

DRUG

sirolimus

For adults, Sirolimus will be administered at 12 mg orally loading dose on day -3, followed by 4 mg orally single morning daily dose (target serum level 3-12 ng/ml by HPLC).

DRUG

tacrolimus

Tacrolimus will be administered intravenously at a dose of 0.03 mg/kg (ideal body weight) q 24h by continuous infusion starting on Day -3. Intravenous Tacrolimus will be discontinued once the patient starts eating and the drug will then be given orally at a dose of approximately 4 times the intravenous dose.

OTHER

laboratory biomarker analysis

laboratory biomarker analysis

PROCEDURE

allogeneic hematopoietic stem cell transplantation

allogeneic hematopoietic stem cell transplantation

PROCEDURE

management of therapy complications

management of therapy complications

PROCEDURE

peripheral blood stem cell transplantation

peripheral blood stem cell transplantation

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Barbara Ann Karmanos Cancer Institute

  lead OTHER

Principal Investigators

• Zaid Al-Kadhimi, M.D. · Barbara Ann Karmanos Cancer Institute

Study Design

Allocation

NA

Purpose

SUPPORTIVE_CARE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-08-31

Primary Completion

2013-05-31

Completion

2013-06-30

Countries

• United States

Study Locations