Fludarabine Phosphate, Low-Dose Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

NCT ID: NCT00005799

Last Updated: 2019-09-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

55 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-11-30

Brief Summary

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This clinical trial studies fludarabine phosphate, low-dose total body irradiation, and donor stem cell transplant in treating patients with hematologic malignancies or kidney cancer. Giving chemotherapy drugs, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood 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). 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 cyclosporine before the transplant and cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

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Detailed Description

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PRIMARY OBJECTIVES:

I. To determine whether stable allogeneic engraftment from unrelated hematopoietic stem cell donors can be safely established using a non-myeloablative conditioning regimen in patients with hematologic malignancies and renal cell carcinoma.

SECONDARY OBJECTIVES:

I. To evaluate whether donor lymphocyte infusion (DLI) can be safely used in patients with mixed or full donor chimerism to eliminate persistent or progressive disease.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2. Patients also undergo low-dose total-body irradiation (TBI) on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) or bone marrow transplantation on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 100 with taper to day 177 and mycophenolate mofetil PO BID on days 0-40 with taper to day 96. Patients with mixed chimerism, persistent or progressive disease, and no evidence of graft-versus-host disease and who have been off immunosuppression for at least 2 weeks undergo DLI over 30 minutes. DLI may be repeated every 65 days for up to 3 doses.

After completion of study treatment, patients are follow-up periodically for 5 years.

Conditions

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Accelerated Phase Chronic Myelogenous Leukemia Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) B-cell Chronic Lymphocytic Leukemia Childhood Acute Lymphoblastic Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission Childhood Chronic Myelogenous Leukemia Childhood Myelodysplastic Syndromes Childhood Renal Cell Carcinoma Chronic Phase Chronic Myelogenous Leukemia Clear Cell Renal Cell Carcinoma de Novo Myelodysplastic Syndromes Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Nodal Marginal Zone B-cell Lymphoma Previously Treated Myelodysplastic Syndromes Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Hodgkin Lymphoma Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Recurrent/Refractory Childhood Hodgkin Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Hairy Cell Leukemia Refractory Multiple Myeloma Relapsing Chronic Myelogenous Leukemia Splenic Marginal Zone Lymphoma Stage III Renal Cell Cancer Stage IV Renal Cell Cancer T-cell Large Granular Lymphocyte Leukemia Type 1 Papillary Renal Cell Carcinoma Type 2 Papillary Renal Cell Carcinoma Waldenström Macroglobulinemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (chemotherapy, TBI, HSCT)

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2. Patients also undergo low-dose TBI on day 0.

TRANSPLANTATION: Patients undergo allogeneic PBSC or bone marrow transplantation on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 100 with taper to day 177 and mycophenolate mofetil PO BID on days 0-40 with taper to day 96. Patients with mixed chimerism, persistent or progressive disease, and no evidence of graft-versus-host disease and who have been off immunosuppression for at least 2 weeks undergo DLI over 30 minutes. DLI may be repeated every 65 days for up to 3 doses.

Group Type EXPERIMENTAL

fludarabine phosphate

Intervention Type DRUG

Given IV

total-body irradiation

Intervention Type RADIATION

Undergo low-dose TBI

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

Undergo nonmyeloablative HSCT

allogeneic bone marrow transplantation

Intervention Type PROCEDURE

Undergo nonmyeloablative allogeneic bone marrow transplantation

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Undergo nonmyeloablative allogeneic PBSC transplantation

therapeutic allogeneic lymphocytes

Intervention Type BIOLOGICAL

Undergo DLI

cyclosporine

Intervention Type DRUG

Given PO

mycophenolate mofetil

Intervention Type DRUG

Given PO

pharmacological study

Intervention Type OTHER

Correlative studies

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

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fludarabine phosphate

Given IV

Intervention Type DRUG

total-body irradiation

Undergo low-dose TBI

Intervention Type RADIATION

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Undergo nonmyeloablative HSCT

Intervention Type PROCEDURE

allogeneic bone marrow transplantation

Undergo nonmyeloablative allogeneic bone marrow transplantation

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Undergo nonmyeloablative allogeneic PBSC transplantation

Intervention Type PROCEDURE

therapeutic allogeneic lymphocytes

Undergo DLI

Intervention Type BIOLOGICAL

cyclosporine

Given PO

Intervention Type DRUG

mycophenolate mofetil

Given PO

Intervention Type DRUG

pharmacological study

Correlative studies

Intervention Type OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

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2-F-ara-AMP Beneflur Fludara TBI bone marrow therapy, allogeneic bone marrow therapy, allogenic transplantation, allogeneic bone marrow transplantation, allogenic bone marrow PBPC transplantation PBSC transplantation peripheral blood progenitor cell transplantation transplantation, peripheral blood stem cell ALLOLYMPH ciclosporin cyclosporin cyclosporin A CYSP Sandimmune Cellcept MMF pharmacological studies

Eligibility Criteria

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Inclusion Criteria

* Age \> 50 years with hematologic malignancies treatable by allogeneic hematopoietic stem cell transplant (HSCT) and all patients with B cell malignancies except those who may be cured by autologous stem cell transplantation (SCT)
* Patients with metastatic renal cell carcinoma with the histologic subtypes of clear cell, papillary and medullary may be accepted regardless of age
* The following diseases will be permitted although other diagnoses can be considered if approved by PCC or the participating institution's patient review committees and the principal investigator

* Non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), Hodgkin lymphoma (HL) - must have received and failed frontline therapy
* Multiple myeloma - must have received prior chemotherapy; consolidation of chemotherapy by autografting prior to nonmyeloablative HSCT is permitted
* Acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) - must be in complete remission and have received cytotoxic chemotherapy at some stage before transplant; patients with molecular or early relapse will be accepted providing a donor is available; patients with persistent or refractory disease will be considered on a case by case basis and transplants must be approved by the institution's patient review committees
* Chronic myelogenous leukemia (CML) - patients will be accepted in chronic phase or accelerated phase; patients who have received prior autografts after high dose therapy or have undergone intensive chemotherapy for either peripheral blood stem cell (PBSC) mobilization or treatment of advanced CML may be enrolled provided they are in complete remission (CR), chronic phase (CP) or accelerated phase (AP)
* Myelodysplastic syndromes (MDS) - all patients with MDS will be eligible for this protocol; however, those patients with MDS and frank AML (\> 30% blasts in bone marrow aspirate by morphology or flow cytometry) will require induction chemotherapy to obtain a complete remission (marrow blasts \< 5%) and remain in complete remission at time of transplant
* Renal cell carcinoma- must have evidence of disease not amenable to surgical cure or metastatic disease by radiological and histological criteria
* DONOR: Human leukocyte antigen (HLA) matched unrelated donor; donors should be matched for HLA -A, -B, -C, -developmentally regulated ribonucleic acid (RNA) binding protein 1(DRB)1 and -class II, DQ beta 1 (DQB) 1; HLA -A and -B loci should be matched at least to the level of resolution; HLA -C, -DRB1, and -DQB1 should be typed at the highest level of resolution available at the time of donor selection; donor must consent to either a bone marrow harvest or PBSC mobilization with filgrastim (G-CSF) arranged through the National Marrow Donor Program (NMDP) or other donor centers

Exclusion Criteria

* Patients with rapidly progressive intermediate or high grade NHL
* Renal cell carcinoma patients with expected survival of less than 6 months

* Bulky disease resulting in severely limited performance status (\< 70%)
* Any vertebral instability
* Any active central nervous system (CNS) involvement with disease
* Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
* Females who are pregnant
* Patients with non-hematological tumors
* Cardiac ejection fraction \< 30%
* Diffusion capacity of the lung for carbon monoxide (DLCO) \< 30% and/or receiving supplementary continuous oxygen
* Significant elevation of bilirubin and transaminases should be discussed at participating institutions' patient review committees in a case by case basis; evidence of synthetic dysfunction or severe cirrhosis will result in patient exclusion
* Karnofsky score \< 50 (except renal cell carcinoma \[RCC\])
* Patients with poorly controlled hypertension on multiple antihypertensives
* Human immunodeficiency virus (HIV) positive patients
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Brenda Sandmaier

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

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City of Hope Medical Center

Duarte, California, United States

Site Status

Stanford University Hospitals and Clinics

Stanford, California, United States

Site Status

University of Colorado

Denver, Colorado, United States

Site Status

Baylor University Medical Center

Dallas, Texas, United States

Site Status

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Universitaet Leipzig

Leipzig, , Germany

Site Status

Countries

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United States Germany

References

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Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.

Reference Type DERIVED
PMID: 32499241 (View on PubMed)

Other Identifiers

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NCI-2012-00667

Identifier Type: REGISTRY

Identifier Source: secondary_id

1463.00

Identifier Type: OTHER

Identifier Source: secondary_id

P01CA018029

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA015704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1463.00

Identifier Type: -

Identifier Source: org_study_id

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