Completed

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

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What is being tested

Total-Body Irradiation

+ Fludarabine Phosphate
+ Mycophenolate Mofetil
Procedure
Drug
Who is being recruted

Acute Lymphoblastic Leukemia in Remission
+10

+ Acute Myeloid Leukemia in Remission
+ Aggressive Non-Hodgkin Lymphoma
Until 75 Years
+53 Eligibility Criteria

See all eligibility criteria

How is the trial designed

Treatment Study

Phase 3
Interventional
Study Start: October 2003

See protocol details

Summary

Principal SponsorFred Hutchinson Cancer Center
Last updated: May 15, 2017
Sourced from a government-validated database.Claim as a partner
Study start date: October 1, 2003Actual date on which the first participant was enrolled.

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. PRIMARY OBJECTIVES: I. To compare overall survival at 3 years after conditioning with 200 cGy TBI alone vs. fludarabine (fludarabine phosphate)/200 cGy TBI in heavily pretreated patients with hematologic malignancies at low/moderate risk for graft rejection. SECONDARY OBJECTIVES: I. To compare the non-relapse mortality 1-year after conditioning in patients who received TBI alone vs. fludarabine/TBI. II. To compare the incidences of graft rejection in patients who received TBI alone vs. fludarabine/TBI. III. To compare the incidences of grades II-IV acute graft-versus-host disease (GVHD) and chronic extensive GVHD. IV. To compare rates of disease progression and/or relapse-related mortality. V. To compare the immune reconstitution and the risks of infections. OUTLINE: NONMYELOABLATIVE CONDITIONING REGIMEN: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2. Patients then undergo low-dose TBI on day 0. ARM II: Patients undergo low-dose TBI on day 0. ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION (PBSCT): After TBI, patients undergo PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (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 mycophenolate mofetil (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. Patients are followed up periodically for 1.5 years and then annually for 5 years post-transplantation.

Official TitleA Multi-center Phase III Study Comparing Nonmyeloablative Conditioning With TBI Versus Fludarabine/TBI for HLA-matched Related Hematopoietic Cell Transplantation for Treatment of Hematologic Malignancies 
Principal SponsorFred Hutchinson Cancer Center
Last updated: May 15, 2017
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
87 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are placed into groups randomly, like flipping a coin. This ensures that the study is fair and unbiased, making the results more reliable. By assigning participants by chance, researchers can better compare treatments without external influences.

Other Ways to Assign Participants
Non-randomized allocation: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.
None (Single-arm trial): If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants are divided into different groups, each receiving a specific treatment at the same time. This helps researchers compare how well different treatments work against each other.

Other Ways to Assign Treatments
Single-group assignment: Everyone gets the same treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Sequential assignment: Participants receive treatments one after another in a specific order, possibly based on individual responses.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Until 75 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
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
Criteria
26 inclusion criteria required to participate
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

Show More Criteria

27 exclusion criteria prevent from participating
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

Show More Criteria

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
2 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
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.
Group II
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.
Study Objectives
Primary Objectives

Percentage of patients surviving as estimated by Kaplan-Meier.
Secondary Objectives

Percentage of NRM as estimated by cumulative incidence methods with competing risks

Percentage of relapse estimated by cumulative incidence methods

Percentage of death following relapse/progression, estimated by cumulative incidence methods

Percentage patients with grades II-IV GHVD, estimated by cumulative incidence methods

Percentage patients with chronic extensive GVHD, estimated by cumulative incidence methods

Donor CD3 chimerism less than 5%

Percentage of patients with progression-free survival, estimated by cumulative incidence methods

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 10 locations
Suspended
OHSU Cancer Institute-Southern RegionMedford, United StatesSee the location
Suspended
Huntsman Cancer Institute/University of UtahSalt Lake City, United States
Suspended
LDS HospitalSalt Lake City, United States
Suspended
VA Puget Sound Health Care SystemSeattle, United States
Completed10 Study Centers