Total-Body Irradiation With or Without Fludarabine Phosphate Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

NCT00075478 | Completed Phase 3 Results DMC

• 4 other identifiers: 1813.00NCI-2009-01532P30CA015704P01CA078902
• Study Type: interventional
• Target: 87
• Locations: 3 countries
• Sites: 10

Brief Summary

This randomized phase III trial is studying total-body irradiation (TBI) and fludarabine phosphate to see how it works compared with TBI alone followed by donor stem cell transplant in treating patients with hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, and radiation therapy before a donor 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 cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after transplant may stop this from happening. It is not yet known whether TBI followed by donor stem cell transplant is more effective with or without fludarabine phosphate in treating hematologic cancer.

Conditions

Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Aggressive Non-Hodgkin Lymphoma; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Diffuse Large B-Cell Lymphoma; Hematopoietic and Lymphoid Cell Neoplasm; Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm; Plasma Cell Myeloma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Percentage of patients surviving as estimated by Kaplan-Meier.

  3 years after transplant

Secondary Outcomes (7)

• Incidence of Non-relapse Mortality

  3 years after transplant

• Incidence of Relapse/Progression

  3 years after transplant

• Incidence of Relapse-related Mortality

  3 years after transplant

• Incidence of Grades II-IV Acute GVHD

  120 days after transplant

• Incidence of Chronic Extensive GVHD

  3 years after transplant

Study Arms (2)

Arm I (chemotherapy, TBI, transplant, GVHD prophylaxis)

EXPERIMENTAL

Patients receive fludarabine phosphate IV on days -4 to -2. Patients then undergo low-dose TBI on day 0. After TBI, patients undergo PBSCT on day 0. Patients receive cyclosporine PO BID on days -3 to 56 in the absence of GVHD. Patients with no evidence of GVHD at day 56 begin a cyclosporine taper and continue the taper until day 180. Patients with evidence of disease progression and no evidence of GVHD prior to day 56 receive tapered doses of cyclosporine for 2 weeks. Patients also receive MMF PO BID on days 0-28 in the absence of GVHD. If treatment for GVHD is required before day 28, MMF is continued until a steroid taper begins.

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

Arm II (TBI, transplant, GVHD prophylaxis)

ACTIVE COMPARATOR

Patients undergo low-dose TBI on day 0. After TBI, patients undergo PBSCT on day 0. Patients receive cyclosporine PO BID on days -3 to 56 in the absence of GVHD. Patients with no evidence of GVHD at day 56 begin a cyclosporine taper and continue the taper until day 180. Patients with evidence of disease progression and no evidence of GVHD prior to day 56 receive tapered doses of cyclosporine for 2 weeks. Patients also receive MMF PO BID on days 0-28 in the absence of GVHD. If treatment for GVHD is required before day 28, MMF is continued until a steroid taper begins.

Procedure: Total-Body Irradiation; Drug: Mycophenolate Mofetil; Drug: Cyclosporine; Procedure: Peripheral Blood Stem Cell Transplantation

Interventions

Total-Body Irradiation PROCEDURE

Undergo TBI

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

Arm I (chemotherapy, TBI, transplant, GVHD prophylaxis); Arm II (TBI, transplant, GVHD prophylaxis)

Fludarabine Phosphate DRUG

Given IV

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

Arm I (chemotherapy, TBI, transplant, GVHD prophylaxis)

Mycophenolate Mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Arm I (chemotherapy, TBI, transplant, GVHD prophylaxis); Arm II (TBI, transplant, GVHD prophylaxis)

Cyclosporine DRUG

Given PO

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

Arm I (chemotherapy, TBI, transplant, GVHD prophylaxis); Arm II (TBI, transplant, GVHD prophylaxis)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo transplantation

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

Arm I (chemotherapy, TBI, transplant, GVHD prophylaxis); Arm II (TBI, transplant, GVHD prophylaxis)

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be not eligible for conventional allogeneic hematopoietic cell transplantation (HCT) and must have disease expected to be stable for at least 100 days without chemotherapy
• An autograft immediately prior (less than 6 months) to nonmyeloablative HCT (tandem approach) is not permitted
• Patients with hematologic malignancies treatable with HCT or with a B cell malignancy except those curable with autologous transplant will be included
• Aggressive non-Hodgkin lymphomas (NHLs) and other histologies such as diffuse large B cell NHL: patients are eligible IF they are not eligible for autologous hematopoietic stem cell transplantation (HSCT), not eligible for conventional myeloablative HSCT, or have failed an autologous HSCT
• Low grade NHL with \< 6 month duration of complete remission (CR) between courses of conventional therapy
• Mantle cell NHL; may be treated in first CR
• Chronic lymphocytic leukemia (CLL) must have either:
• Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine phosphate (FLU) (or another nucleoside analog, e.g. cladribine \[2-CDA\], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog)
• Failed FLU-cyclophosphamide \[CY\]-rituximab (FCR) combination chemotherapy at any time point
• Have "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR
• Or patients with a diagnosis of CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL
• Hodgkin lymphoma (HL): must have received and failed frontline therapy; patients must have failed or were not eligible for autologous transplant
• Multiple myeloma (MM): must have chemosensitive disease after failed autografting (an autografting immediately prior \[within 6 months\] to nonmyeloablative HCT \[tandem approach\] is not permitted)
• Acute myeloid leukemia (AML): must have \< 5% marrow blasts at the time of transplant and be beyond first CR
• Acute lymphocytic leukemia (ALL): must have \< 5% marrow blasts at the time of transplant and be beyond first CR

You may not qualify if:

• Eligible for a high priority curative autologous transplant
• Patients with rapidly progressive, aggressive NHL unless in minimal disease state
• Patients with chronic myelomonocytic leukemia
• Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML
• Life expectancy severely limited by diseases other than malignancy
• Any current central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
• Fertile men or women unwilling to use contraceptives during and for up to 12 months post treatment
• Female patients who are pregnant or breastfeeding
• Human immunodeficiency virus (HIV) positive patients
• Patients with active non-hematological malignancies (except localized non-melanoma skin malignancies)
• Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a \> 20% risk of disease recurrence
• Fungal infections with radiological progression after receipt of amphotericin formulation or mold-active azoles for greater than 1 month
• Patients with active bacterial or fungal infections unresponsive to medical therapy
• Karnofsky score \< 50 for adult patients
• Lansky-Play performance score \< 50 for pediatric patients

Sponsors & Collaborators

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

Study Sites (10)

OHSU Cancer Institute-Southern Region

Medford, Oregon, 97504, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

LDS Hospital

Salt Lake City, Utah, 84143, United States

Location

VA Puget Sound Health Care System

Seattle, Washington, 98101, 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

Medizinische Univ Klinik Koln

Cologne, 50924, Germany

Location

Universitaet Leipzig

Leipzig, D-04103, Germany

Location

University of Tuebingen-Germany

Tübingen, D-72076, Germany

Location

University of Torino

Torino, 10126, Italy

Location

Related Publications (2)

• Kornblit B, Maloney DG, Storb R, Storek J, Hari P, Vucinic V, Maziarz RT, Chauncey TR, Pulsipher MA, Bruno B, Petersen FB, Bethge WA, Hubel K, Bouvier ME, Fukuda T, Storer BE, Sandmaier BM. Fludarabine and 2-Gy TBI is superior to 2 Gy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial. Biol Blood Marrow Transplant. 2013 Sep;19(9):1340-7. doi: 10.1016/j.bbmt.2013.06.002. Epub 2013 Jun 11.

  PMID: 23769990 BACKGROUND

• 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, Chronic-Phase; Lymphoma, Large B-Cell, Diffuse; Hematologic Neoplasms; Lymphoma, Mantle-Cell; Myelodysplastic-Myeloproliferative Diseases; Multiple Myeloma; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Waldenstrom Macroglobulinemia

Interventions

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

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; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, B-Cell; Leukemia, Lymphoid

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Brenda Sandmaier
• Organization: Fred Hutchinson Cancer Research Center/

bsandmai@fhcrc.org

206-667-4961

Study Officials

• Brenda Sandmaier

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 9, 2004
• First Posted: January 12, 2004
• Study Start: October 1, 2003
• Primary Completion: February 1, 2014
• Study Completion: February 2, 2014
• Last Updated: May 15, 2017
• Results First Posted: May 19, 2014

Record last verified: 2017-04

Locations

IT (1); US (6); DE (3)