Total-Body Irradiation and Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

NCT00027820 | Completed Phase 1 DMC

• 4 other identifiers: 1641.00NCI-2012-00591P30CA015704P01CA018029
• Study Type: interventional
• Target: 106
• Locations: 3 countries
• Sites: 10

Brief Summary

This phase I/II trial studies whether a new kind of blood stem cell (bone marrow) transplant, that may be less toxic, is able to treat underlying blood cancer. Stem cells are "seed cells" necessary to make blood cells. Researchers want to see if using less radiation and less chemotherapy with new immune suppressing drugs will enable a stem cell transplant to work. Researchers are hoping to see a mixture of recipient and donor stem cells after transplant. This mixture of donor and recipient stem cells is called "mixed-chimerism". Researchers hope to see these donor cells eliminate tumor cells. This is called a "graft-versus-leukemia" response.

Conditions

Adult Acute Myeloid Leukemia in Remission; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndrome; Childhood Renal Cell Carcinoma; Chronic Myelomonocytic Leukemia; Clear Cell Renal Cell Carcinoma; de Novo Myelodysplastic Syndrome; Metastatic Renal Cell Cancer; Previously Treated Myelodysplastic Syndrome; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Renal Medullary Carcinoma; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• Risk of true graft rejection in patients with and without preceding chemotherapy

  The goal is to reduce the risk in patients without preceding chemotherapy to \< 20% and with preceding chemotherapy to \< 10%.

  Up to 5 years

• Risk of grades II-IV acute GVHD in those patients with sustained engraftment

  The goal is to reduce the incidence of grades II-IV acute GVHD from 50% to less than 35% in patients with sustained engraftment by increasing the dosing of MMF to every 8 hours. The impact of the enhanced post-grafting immunosuppression on objective measures of GVHD will be described. These include doses and duration of immunosuppression (in particular corticosteroids) and number of GVHD treatment regimens used within the first year. These parameters will be compared to the results of protocol 1463.

  Up to 5 years

Secondary Outcomes (3)

• Incidence of reversing impending graft rejection (less than 40% donor cluster of differentiation [CD]3+ T cell chimerism)

  Up to 5 years

• Overall survival

  Up to 5 years

• Progression-free survival

  Up to 5 years

Study Arms (1)

Treatment (PBSCT)

EXPERIMENTAL

REDUCED-INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV on days -4, -3, and -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 100 with taper to day 177 and mycophenolate mofetil PO every 8 hours on days 0-40 with taper to day 96.

Drug: Fludarabine Phosphate; Radiation: Total-Body Irradiation; Procedure: Peripheral Blood Stem Cell Transplantation; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclosporine; Drug: Mycophenolate Mofetil

Interventions

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, SH T 586

Treatment (PBSCT)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: TBI, Total Body Irradiation, Whole-Body Irradiation

Treatment (PBSCT)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo nonmyeloablative PBSCT

Also known as: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

Treatment (PBSCT)

Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo nonmyeloablative PBSCT

Also known as: Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplantation, NST

Treatment (PBSCT)

Cyclosporine DRUG

Given PO

Also known as: 27-400, CsA, Neoral, OL 27-400, Sandimmun

Treatment (PBSCT)

Mycophenolate Mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Treatment (PBSCT)

Eligibility Criteria

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

You may qualify if:

• Ages \> 50 years with hematologic malignancies treatable by unrelated hematopoietic stem cell transplantation (HSCT)
• 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:
• Intermediate or high grade non-Hodgkin lymphoma (NHL) - not eligible for autologous HSCT or after failed autologous HSCT
• Low grade NHL - with \< 6 month duration of complete remission (CR) between courses of conventional therapy
• Chronic lymphocytic leukemia (CLL) - must have failed two lines of conventional therapy and be refractory to fludarabine
• Hodgkin's disease (HD) - must have received and failed frontline therapy
• Multiple myeloma (MM) - must have received prior chemotherapy; consolidation of chemotherapy by autografting prior to nonmyeloablative HSCT is permitted
• Acute myeloid leukemia (AML) - must have \< 5% marrow blasts at the time of transplant
• Acute lymphoblastic leukemia - must have \< 5% blasts at the time of transplant
• 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 with PBSC autologous or conventional HSCT for advanced CML may be enrolled provided they are in CR or chronic phase (CP) and have \< 5% marrow blasts at time of transplant
• Myelodysplastic syndromes (MDS)/myeloproliferative disorder (MPD) - only patients with MDS/refractory anemia (RA) or MDS/refractory anemia with ringed sideroblasts (RARS) will be eligible for this protocol; additionally patients with myeloproliferative syndromes (MPS) will be eligible; those patients with MDS or MPS with \> 5% marrow blasts (including those with transformation to AML) must receive cytotoxic chemotherapy and achieve \< 5% marrow blasts at time of transplant
• Renal cell carcinoma - must have evidence of disease not amenable to surgical cure or history of or active metastatic disease by radiological and histologic criteria
• DONOR: FHCRC matching allowed will be grade 1.0 to 2.1; unrelated donors who are prospectively:
• Matched for human leukocyte antigen (HLA)-A, B, C, DRB1 and DQB1 by high resolution typing

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
• Disease resulting in severely limited performance status (\< 70%)
• Any vertebral instability
• History of brain metastases
• Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
• 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 except renal cell carcinoma
• Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
• Cardiac ejection fraction \< 35%; ejection fraction is required if there is a history of anthracycline exposure or history of cardiac disease
• Diffusion capacity of the lung for carbon monoxide (DLCO) \< 40% and/or receiving supplementary continuous oxygen
• The FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules
• Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \> 3 mg/dL, and symptomatic biliary disease

Sponsors & Collaborators

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

Study Sites (10)

University of Arizona Health Sciences Center

Tucson, Arizona, 85724, United States

Location

Stanford University Hospitals and Clinics

Stanford, California, 94305, United States

Location

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Baylor Medical Center at Garland

Garland, Texas, 75042, 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

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Universitaet Leipzig

Leipzig, D-04103, Germany

Location

University of Torino

Torino, 10126, Italy

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, Myelomonocytic, Chronic; Carcinoma, Renal Cell; Leukemia, Plasma Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Hodgkin Disease; Lymphoma, Non-Hodgkin; Anemia, Refractory; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

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

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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; Multiple Myeloma; Neoplasms, Plasma Cell; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Lymphatic Diseases; Lymphoma; Anemia; Myelodysplastic Syndromes; Leukemia, B-Cell

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; 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: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2001
• First Posted: January 27, 2003
• Study Start: August 1, 2001
• Primary Completion: September 1, 2004
• Study Completion: September 5, 2004
• Last Updated: December 20, 2019

Record last verified: 2019-12

Locations

IT (1); US (8); DE (1)