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NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders

Phase 2
Completed
Conditions
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Chronic Myeloproliferative Disorders
Fanconi Anemia
Aplastic Anemia
Leukemia
Lymphoma
Interventions
Biological: anti-thymocyte globulin
Biological: graft-versus-tumor induction therapy
Biological: sargramostim
Biological: therapeutic allogeneic lymphocytes
Procedure: allogeneic bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Procedure: umbilical cord blood transplantation
Registration Number
NCT00053989
Lead Sponsor
Roswell Park Cancer Institute
Brief Summary

RATIONALE: Giving low doses of chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving immunosuppressive therapy before or after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well chemotherapy followed by donor peripheral stem cell transplant works in treating patients with hematologic cancer or aplastic anemia.

Detailed Description

OBJECTIVES:

* Determine the safety and toxic effects of nonmyeloablative allogeneic peripheral blood stem cell transplantation in patients with a hematologic malignancy or aplastic anemia.

* Determine clinical response and overall outcome of patients treated with this regimen.

* Determine the incidence of graft-vs-tumor effect, graft-vs-host disease, and chimerism in patients treated with this regimen.

OUTLINE:

* Preparative regimen:

* Matched related and unrelated donor transplantation:

* Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine IV over 30 minutes on days -5 to -1.

* Cord blood transplantation:

* Patients receive the same regimen as above plus anti-thymocyte globulin IV over 4 hours on days -3 to -1.

* Graft-vs-host disease (GVHD) prophylaxis:

* Matched related and unrelated donor transplantation:

* Patients receive oral tacrolimus (or IV) once daily and oral mycophenolate mofetil (MMF) (or IV) twice daily on days -1 to 60 followed by tapering\* of this regimen. Patients then receive methotrexate IV on days 1, 3, and 6.

* Cord blood transplantation:

* Patients receive tacrolimus and MMF in the same regimen as above plus methylprednisolone twice daily on days 1-19 or until blood counts recover.

* Allogeneic stem cell reinfusion: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0. Patients then receive sargramostim (GM-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.

* Donor lymphocyte infusion (DLI): Patients not converting to 100% donor T-cell chimerism by day 120 and showing signs of progresson of disease after tacrolimus and MMF withdrawal may receive DLI every 8 weeks for up to 3 infusions. Cord blood recipients do not receive DLI.

Patients are followed at day 100-120, every 3 months for 2 years, and then every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 6-7 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
41
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
All patientsperipheral blood stem cell transplantationAll patients enrolled on study
All patientstherapeutic allogeneic lymphocytesAll patients enrolled on study
All patientstacrolimusAll patients enrolled on study
All patientssargramostimAll patients enrolled on study
All patientsmethylprednisoloneAll patients enrolled on study
All patientsanti-thymocyte globulinAll patients enrolled on study
All patientsgraft-versus-tumor induction therapyAll patients enrolled on study
All patientscyclophosphamideAll patients enrolled on study
All patientsfludarabine phosphateAll patients enrolled on study
All patientsmycophenolate mofetilAll patients enrolled on study
All patientsallogeneic bone marrow transplantationAll patients enrolled on study
All patientsumbilical cord blood transplantationAll patients enrolled on study
Primary Outcome Measures
NameTimeMethod
Day 100 Best Responsefrom start of conditioning on day -6 or -5 through day +100 after HSC infusion

Best disease response measured within 100 days from hematopoietic stem cell (HSC) infusion on day 0 using disease specific response criteria defined in the protocol

Day 100 TRMfrom start or conditioning (day -6 or -5) through day +100 after HSC infusion

treatment related mortality within 100 days from hematopoietic stem cell (HSC) infusion on day 0

Secondary Outcome Measures
NameTimeMethod
PFS1 year

Progression free survival defined as time from HSC infusion (day 0) until progression of disease or death due to any cause. Patients are censored if alive without disease progression through 1 year after HSC infusion

Acute GvHDDay +100

overall grade II-IV acute GvHD

OS1 year

Overall survival with events defined as death due to any cause and censored patients are alive as of 1 year post HSC infusion

Trial Locations

Locations (1)

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

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