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

NCT00005799 | Completed

• 4 other identifiers: 1463.00NCI-2012-00667P01CA018029P30CA015704
• Study Type: interventional
• Target: 55
• Locations: 2 countries
• Sites: 7

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Establishment of an allograft as defined by stable mixed chimerism or full donor chimerism

  Engraftment will be assessed separately among patients who receive bone marrow and patients who receive PBSC. Patients with low-risk and high-risk disease will be assessed separately.

  At day 56

Secondary Outcomes (13)

• Disease-free survival

  Up to 200 days

• Relapse

  Assessed up to 5 years

• Disease-related mortality

  Before day 200

• Response of malignancy to DLI

  Assessed up to 5 years

• Incidence of myelosuppression

  Greater than 2 days after initial PBSC infusion

Study Arms (1)

Treatment (chemotherapy, TBI, HSCT)

EXPERIMENTAL

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.

Drug: fludarabine phosphate; Radiation: total-body irradiation; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Procedure: allogeneic bone marrow transplantation; Procedure: peripheral blood stem cell transplantation; Biological: therapeutic allogeneic lymphocytes; Drug: cyclosporine; Drug: mycophenolate mofetil; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

fludarabine phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Treatment (chemotherapy, TBI, HSCT)

total-body irradiation RADIATION

Undergo low-dose TBI

Also known as: TBI

Treatment (chemotherapy, TBI, HSCT)

nonmyeloablative allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo nonmyeloablative HSCT

Treatment (chemotherapy, TBI, HSCT)

allogeneic bone marrow transplantation PROCEDURE

Undergo nonmyeloablative allogeneic bone marrow transplantation

Also known as: bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow

Treatment (chemotherapy, TBI, HSCT)

peripheral blood stem cell transplantation PROCEDURE

Undergo nonmyeloablative allogeneic PBSC transplantation

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Treatment (chemotherapy, TBI, HSCT)

therapeutic allogeneic lymphocytes BIOLOGICAL

Undergo DLI

Also known as: ALLOLYMPH

Treatment (chemotherapy, TBI, HSCT)

cyclosporine DRUG

Given PO

Also known as: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune

Treatment (chemotherapy, TBI, HSCT)

mycophenolate mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Treatment (chemotherapy, TBI, HSCT)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (chemotherapy, TBI, HSCT)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (chemotherapy, TBI, HSCT)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Karnofsky score \< 50 (except renal cell carcinoma \[RCC\])
• Patients with poorly controlled hypertension on multiple antihypertensives
• Human immunodeficiency virus (HIV) positive patients

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (7)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Stanford University Hospitals and Clinics

Stanford, California, 94305, United States

Location

University of Colorado

Denver, Colorado, 80217-3364, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Universitaet Leipzig

Leipzig, D-04103, Germany

Location

Related Publications (1)

• 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.

  PMID: 32499241 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Congenital Abnormalities; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Chronic-Phase; Carcinoma, Renal Cell; Lymphoma, B-Cell, Marginal Zone; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Hodgkin Disease; Lymphoma, T-Cell, Cutaneous; Lymphoma, Follicular; Mycosis Fungoides; Sezary Syndrome; Recurrence; Leukemia, Hairy Cell; Multiple Myeloma; Leukemia, Large Granular Lymphocytic; Waldenstrom Macroglobulinemia

Interventions

fludarabine phosphate; Whole-Body Irradiation; Transplantation; Peripheral Blood Stem Cell Transplantation; Cyclosporine; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Lymphoma, B-Cell; Lymphoma; Lymphoma, T-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, T-Cell

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Surgical Procedures, Operative; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Officials

• Brenda Sandmaier

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2000
• First Posted: April 2, 2004
• Study Start: November 1, 1999
• Primary Completion: July 1, 2002
• Last Updated: September 10, 2019

Record last verified: 2019-09

Locations

US (6); DE (1)