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

Sponsor

Wake Forest University Health Sciences (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02248597

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

99.2

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease Hematopoietic/Lymphoid Cancer	Drug: fludarabine phosphate Drug: busulfan Drug: cyclophosphamide Procedure: allogeneic hematopoietic stem cell transplantation Drug: tacrolimus Drug: mycophenolate mofetil	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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:

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 25, 2015

Actual Primary Completion Date :

Jan 18, 2022

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (stem cell transplant with GVHD prophylaxis) PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV 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. Allogeneic hematopoietic stem cell transplantation	Drug: fludarabine phosphate Given IV Other Names: 2-F-ara-AMP Beneflur Fludara Drug: busulfan Given IV Other Names: BSF BU Misulfan Mitosan Myeloleukon Drug: cyclophosphamide Given IV Other Names: CPM CTX Cytoxan Endoxan Endoxana Procedure: allogeneic hematopoietic stem cell transplantation Undergo myeloablative or reduced intensity allogeneic stem cell transplant Drug: tacrolimus Other Names: FK 506 Prograf Drug: mycophenolate mofetil Other Names: Cellcept MMF

Arm

Intervention/Treatment

Experimental: Treatment (stem cell transplant with GVHD prophylaxis)

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV 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. Allogeneic hematopoietic stem cell transplantation

Drug: fludarabine phosphate

Given IV

Other Names:

2-F-ara-AMP

Beneflur

Fludara

Drug: busulfan

Given IV

Other Names:

BSF

Misulfan

Mitosan

Myeloleukon

Drug: cyclophosphamide

Given IV

Other Names:

CPM

CTX

Cytoxan

Endoxan

Endoxana

Procedure: allogeneic hematopoietic stem cell transplantation

Undergo myeloablative or reduced intensity allogeneic stem cell transplant

Drug: tacrolimus

Other Names:

FK 506

Prograf

Drug: mycophenolate mofetil

Other Names:

Cellcept

MMF

Outcome Measures

Primary Outcome Measures

12 month disease free survival probability [At 12 months]
The proportion 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.

Secondary Outcome Measures

Rate of acute GvHD [At 12 months]
Calculating the rates of acute GvHD in the study population at twelve months with a 95% confidence interval.
Rate of chronic GvHD [At 12 months]
Calculating the rates of acute GvHD in the study population at twelve months with a 95% confidence interval.
Overall survival [At 12 months]
The survival function will be estimated and plotted using the method of Kaplan and Meier.
Relapse (or death) [At 12 months]
Calculating the proportion of patients who experience death by one year and construct a corresponding 95% confidence interval using the normal approximation for binomial proportions.
Relapse-free mortality [At 12 months]
The cumulative incidence function in the presence of relapse will be estimated.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 69 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.