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

NCT ID: NCT01116232

Last Updated: 2019-03-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2013-06-30

Brief 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.

Detailed Description

OBJECTIVES:

Primary

• Determine the incidence and severity of acute graft-vs-host disease (GVHD) in patients with hematologic malignancies undergoing donor peripheral blood stem cell transplantation who are receiving sirolimus, tacrolimus, anti-thymocyte globulin, and rituximab as GVHD prophylaxis.
• Assess time to engraftment absolute neutrophil count (> 0.5 x 10^9/L for 3 consecutive days) and platelet count (> 20 x 10^9/L for 3 consecutive days) in these patients.
• Determine the safety, as defined by serious adverse events and adverse events related to this immunosuppressive regimen, in the first 6 months after treatment.

Secondary

• Assess the incidence of chronic GVHD measured within 2 years after transplantation.
• Assess overall and disease-free survival at 2 years after transplantation.
• Examine the incidence of opportunistic infections including fungal infections, pneumocystis carinii pneumonia, and viral infections (cytomegalovirus, varicella zoster virus, herpes simplex virus, BK virus, Epstein-Barr virus, and post-transplant lymphoproliferative disorder).
• Assess the incidence of thrombotic microangiopathy within 100 days of transplantation.
• Perform immunocorrelative studies, including T-cell, B-cell, NK-cell, regulatory cell, and allo-reactive T-cell measurement studies via flow cytometry, at 30, 60, 90, and 180 days after transplantation.

OUTLINE: Patients receive rituximab IV on days -7 and 3, tacrolimus IV continuously (may switch to orally when the patient is able to eat) and oral sirolimus beginning on day -3, and anti-thymocyte globulin IV over 6 hours on days -3 to -1. Tacrolimus and sirolimus are tapered at the discretion of the treating physician.

All patients also receive a standard transplant-preparative regimen and undergo transplantation on day 0.

Blood samples are collected before the preparative regimen and at 30, 60, 90, and 180 days after transplantation for correlative immunologic studies.

After completion of study treatment, patients are followed up for 2 years.

Conditions

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

Study Design

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

Study Groups

anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,

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

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;

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).

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.

Group Type: EXPERIMENTAL

anti-thymocyte globulin

Intervention Type: BIOLOGICAL

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.

rituximab

Intervention Type: BIOLOGICAL

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.

sirolimus

Intervention Type: DRUG

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).

tacrolimus

Intervention Type: DRUG

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.

laboratory biomarker analysis

Intervention Type: OTHER

laboratory biomarker analysis

allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

allogeneic hematopoietic stem cell transplantation

management of therapy complications

Intervention Type: PROCEDURE

management of therapy complications

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Interventions

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

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).

Intervention Type: 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.

Intervention Type: DRUG

laboratory biomarker analysis

laboratory biomarker analysis

Intervention Type: OTHER

allogeneic hematopoietic stem cell transplantation

allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

management of therapy complications

management of therapy complications

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Other Intervention Names

Rituxan®; Rapamune®; Prograf

Eligibility Criteria

Inclusion Criteria

• No ascites
• No HIV positivity
• No active hepatitis B or C virus infection
• No known contraindication to the administration of sirolimus, tacrolimus, anti-thymocyte globulin, or rituximab

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Not on home oxygen

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Barbara Ann Karmanos Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Zaid Al-Kadhimi

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zaid Al-Kadhimi, M.D.

Role: PRINCIPAL_INVESTIGATOR

Barbara Ann Karmanos Cancer Institute

Locations

Karmanos Cancer Institute

Detroit, Michigan, United States

Countries

United States

Related Links

http://cancer.gov/clinicaltrials

Clinical trial summary from the National Cancer Institute's PDQ® database

Other Identifiers

P30CA022453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U4781s

Identifier Type: OTHER

Identifier Source: secondary_id

2009-150

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000671822

Identifier Type: -

Identifier Source: org_study_id

NCT01534767

Identifier Type: -

Identifier Source: nct_alias