Early Administration of ATG Followed by Cyclophosphamide, Busulfan and Fludarabine Before a Donor Stem Cell Transplant in Patients With Hematological Cancer

Phase 2

Completed

• Conditions: Myeloproliferative Disorders; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases
• Interventions: Biological: anti-thymocyte globulin; Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: methotrexate; Drug: tacrolimus; Procedure: nonmyeloablative allogeneic HSCT

• Registration Number: NCT00787761
• Lead Sponsor: Northside Hospital, Inc.

Brief Summary

RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop 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 antithymocyte globulin before the transplant and tacrolimus and methotrexate after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving antithymocyte globulin together with cyclophosphamide, busulfan, and fludarabine works in treating patients with hematological cancer or kidney cancer undergoing donor stem cell transplant.

Detailed Description

OBJECTIVES:

* To assess the percentage of patients with hematological malignancies or renal cell carcinoma who achieve \> 90% donor T-cell chimerism at 30 days after treatment with reduced-intensity conditioning comprising low-dose anti-thymocyte globulin, low-dose cyclophosphamide, busulfan, and fludarabine phosphate followed by allogeneic peripheral blood progenitor cell transplantation from a matched related donor.

* To assess the incidence of severe (grade 3 or 4) acute graft-versus-host disease (GVHD) and extensive chronic GVHD in these patients.

* To assess whether this regimen is associated with reduced transplant-related toxicity and increased tolerability in these patients.

* To assess the overall safety of this conditioning regimen as measured by 6-month transplant-related mortality in these patients.

* To determine the efficacy of this regimen in inducing durable remissions in these patients.

OUTLINE:

* Reduced-intensity conditioning (RIC): Patients receive anti-thymocyte globulin IV over 4-6 hours on day -16 and over 6-8 hours on day -15, fludarabine phosphate IV over 30 minutes on days -7 to -3, busulfan IV over 3 hours on days -4 and -3, and cyclophosphamide IV over 1-2 hours on day -2.

* Transplantation: Patients undergo allogeneic peripheral blood progenitor cell transplantation on day 0.

* Graft-vs-host disease (GVHD) prophylaxis: Patients receive oral tacrolimus every 12 hours on days -1 to 90, followed by a taper until day 150. Patients also receive methotrexate IV on days 1, 3, and 6.

Blood samples are collected periodically for pharmacokinetic studies of anti-thymocyte globulin and PCR analysis for chimerism.

After completion of study therapy, patients are followed periodically for up to 3 years.

Study Timeline

• Study Start: 2007-04
• Study First Submitted: 2008-11-07
• Study First Submitted QC: 2008-11-07
• Study First Posted: 2008-11-10
• Primary Completion: 2010-07
• Study Completion: 2012-05
• Results First Submitted: 2012-07-09
• Status Verified: 2012-08
• Results First Submitted QC: 2012-08-29
• Last Update Submitted: 2012-08-29
• Results First Posted: 2012-10-01
• Last Update Posted: 2012-10-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ATG, Cytoxan, Bu/Flu based Allogeneic Transplant	anti-thymocyte globulin	All patients will receive an ATG, Cyclosphosphamide, Busulfan and Fludarabine based Allogeneic Transplant
ATG, Cytoxan, Bu/Flu based Allogeneic Transplant	busulfan	All patients will receive an ATG, Cyclosphosphamide, Busulfan and Fludarabine based Allogeneic Transplant
ATG, Cytoxan, Bu/Flu based Allogeneic Transplant	nonmyeloablative allogeneic HSCT	All patients will receive an ATG, Cyclosphosphamide, Busulfan and Fludarabine based Allogeneic Transplant
ATG, Cytoxan, Bu/Flu based Allogeneic Transplant	cyclophosphamide	All patients will receive an ATG, Cyclosphosphamide, Busulfan and Fludarabine based Allogeneic Transplant
ATG, Cytoxan, Bu/Flu based Allogeneic Transplant	fludarabine phosphate	All patients will receive an ATG, Cyclosphosphamide, Busulfan and Fludarabine based Allogeneic Transplant
ATG, Cytoxan, Bu/Flu based Allogeneic Transplant	methotrexate	All patients will receive an ATG, Cyclosphosphamide, Busulfan and Fludarabine based Allogeneic Transplant
ATG, Cytoxan, Bu/Flu based Allogeneic Transplant	tacrolimus	All patients will receive an ATG, Cyclosphosphamide, Busulfan and Fludarabine based Allogeneic Transplant

Primary Outcome Measures

Name	Time	Method
Achievement of > 90% (Full) Donor Chimerism in the T-cell Lineage as Measured by PCR at Day 30 Post-transplantation	Day 30	Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.

Secondary Outcome Measures

Name	Time	Method
T-cell and Myeloid Chimerism at Days 90 Post-transplantation (>90% Chimerism)	Day 90	Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
T-cell and Myeloid Chimerism at Days 180 Post-transplantation (>90%)	180 days	Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Number of Patients Who Experience Severe (Grade 3 or 4) Acute Graft-versus-host Disease	Day 100	number of patients who experienced post-transplant complication (GVHD) as seen by clinical evidence including but not limited to skin rash, elevated liver function tests, nausea/vomiting/diarrhea.
Number of Patients Experiencing Extensive Chronic Graft Versus Host Disease (GVHD)	2 years	Patients who had post-transplant complication (GVHD) as seen by clinical evidence including but not limited to skin rash, elevated liver function tests, nausea/vomiting/diarrhea.
Non-relapse Mortality (NRM) at Day 180 Post-transplantation	Day 180	non-relapse mortality refers to the death of a patient for causes other than relapsed disease.
Disease-free Survival (DFS) at 24 Months	24 months	Disease Free survival is measured by the amount of time a patient spends in a disease free state after being transplanted.
Overall Survival (OS) at 24 Months	24 months	Overall survival refers to the length of time a patient is alive after transplant regardless of whether they have progressive or relapsed disease.

Trial Locations

Locations (1)

Blood and Marrow Transplant Group of Georgia; 🇺🇸 Atlanta, Georgia, United States