Donor Stem Cell Transplant Followed by Cyclophosphamide in Treating Patients With Hematological Diseases

Graft Versus Host Disease Clinical Trial

Official title:

Haploidentical Stem Cell Transplant Using Post Transplant Cyclophosphamide for GvHD Prophylaxis: A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02248597
• Other study ID #: IRB00029210
• Secondary ID: NCI-2014-01898CC
• Status: Completed
• Phase: Phase 2
• Start date: February 25, 2015
• Est. completion date: January 18, 2023

Study information

• Verified date: October 2023
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This pilot clinical trial studies donor stem cell transplant followed by cyclophosphamide in treating patients with hematological diseases. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving cyclophosphamide after the transplant may stop this from happening.

Description:

PRIMARY OBJECTIVES:

I. To determine if haploidentical stem cell transplant using post-transplant cyclophosphamide results in 60% or better disease free survival (DFS) at 12 months at our institution.

SECONDARY OBJECTIVES:

I. To determine the rate of acute and chronic graft-versus-host disease (GvHD), non-relapse mortality, and relapse.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) once daily (QD) on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2

TRANSPLANT: Patients undergo stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: January 18, 2023
• Est. primary completion date: January 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

Inclusion Criteria:

• Diagnosis of a hematological malignancy requiring an allogeneic stem cell transplant consistent with the standard of care

• Remission of any acute hematologic malignancy or adequate disease control for chronic malignancies.

• Ages 18-69 years old.

• Available familial haploidentical (4 to 6 out of 8 HLA loci-matched) donor

Exclusion Criteria:

• Significant organ dysfunction defined as: LV EF < 50% (evaluated by echocardiogram or MRI), DLCO or FEV1 < 65% predicted, AST/ALT > 2.5 x ULN, Bilirubin > 1.5 x ULN, Serum creatinine > 2mg/dL, dialysis, or prior renal transplant

• HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) are not excluded from participation)

• Positive pregnancy test for women of childbearing age.

• Major anticipated illness or organ failure incompatible with survival form transplant.

• Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and informed consent impossible.

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease
• Hematopoietic/Lymphoid Cancer

Intervention

Drug:
• fludarabine phosphate
Given IV
• busulfan
Given IV
• cyclophosphamide
Given IV

Procedure:
• allogeneic hematopoietic stem cell transplantation
Undergo myeloablative or reduced intensity allogeneic stem cell transplant

Drug:
• tacrolimus

• mycophenolate mofetil

Locations

Country	Name	City	State
United States	Comprehensive Cancer Center of Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	12 Month Disease Free Survival Probability	The percentage of patients who experience death or disease relapse by one year will be calculated and a corresponding 95% confidence interval will be constructed using the normal approximation for binomial proportions. The survival function will be estimated and plotted using the method of Kaplan and Meier.	At 12 months
Secondary	Rate of Acute GvHD	Kaplan-Meier estimation of the rate of acute GvHD in the study population at one year with a 95% confidence interval.	12 months
Secondary	Overall Survival	The survival function will be estimated and plotted using the method of Kaplan and Meier.	At 12 months
Secondary	Progression Free Survival	Kaplan-Meier estimation of the percentage of patients who are alive without progressive disease at one year.	At 12 months
Secondary	Relapse-free Mortality	Non-relapse mortality will be defined as time from registration to death due to anything other than relapse of hematological malignancy. Patients who relapse will be treated as a competing risk.	At 12 months