NCT00303719 · REGISTRY CONDITION SEARCH

Allogeneic Bone Marrow Transplantation Using Less Intensive Therapy

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: TERMINATED
Registry last update: 2020-05-12

RATIONALE: A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy, or that have become cancer. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclophosphamide and fludarabine together with total-body irradiation followed by cyclosporine and mycophenolate mofetil before the transplant may stop this from happening. PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy followed by cyclosporine and mycophenolate mofetil works in treating patients who are undergoing a donor stem cell transplant for hematologic cancer, metastatic breast cancer, or kidney cancer.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Neutrophil and Donor Cell Engraftment

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outcome · POSTED

Serious Adverse Events

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outcome · POSTED

Transplant Related Mortality

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outcome · POSTED

Overall Survival

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outcome · POSTED

Acute Graft-Versus-Host Disease

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: Standard patients will be enrolled into Arms 1-6. High risk patients (transplant with aplasia) will be considered separately in Arm 7. * Age and Graft criteria (all patients) * Patient's \< or = 75 years old with a 5/6 or 6/6 related donor match are eligible. * Patient's \< or = 75 years who have a 7-8/8 HLA-A,B,C,DRB1 allele matched unrelated volunteer marrow and/or peripheral blood stem cell (PBSC) donor match are eligible. * Disease Criteria (standard risk patients) * Acute myelogenous leukemia * Acute lymphocytic leukemia * Chronic myelogenous leukemia all types except blast crisis (note treated blast crisis in chronic phase is eligible). * Non-Hodgkins lymphoma (NHL), Hodgkins, chronic lymphocytic leukemia, multiple myeloma demonstrating chemosensitive disease * Acquired bone marrow failure syndromes * Myelodysplastic syndrome of all subtypes including refractory anemia (RA) or all IPSS categories if severe pancytopenia, transfusion requirements not responsive to therapy, or high risk cytogenetics. Blasts must be less than 5%. If \>5% requires therapy (induction or Hypomethylating agents) pre-transplant to decrease disease burden. * Renal cell cancer, * Chronic myeloproliferative disorder, i.e. myelofibrosis * Disease Criteria (High risk patients on Arm 7) * Patients with refractory leukemia or MDS may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody. These high risk patients will be analyzed separately in Arm 7. * Adequate organ function and performance status (all patients) Exclusion Criteria: * Pregnancy or breast feeding * Evidence of HIV infection or known HIV positive serology * Active serious infection * Congenital bone marrow failure syndrome * Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI) * Chronic myelogenous leukemia (CML) in refractory blast crisis * Intermediate or high grade NHL, mantle cell NHL, and Hodgkins disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky. * Multiple Myeloma progressive on salvage chemotherapy. DONOR ELIGIBILITY * Related will undergo apheresis - if donor is unable to undergo apheresis, a bone marrow harvest is acceptable; unrelated volunteer donors must be able to undergo bone marrow harvest or apheresis. * All donors must be able to give informed consent. * Donors weighing less than 40 kg (children) will need evaluation by a pediatrician for suitability of the apheresis procedure. Informed consent must be obtained from parent or guardian as applicable for minors.
healthy Volunteers: false
maximum Age: 75 Years
sex: ALL
std Ages: CHILD
ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Nonmyeloablative conditioning using fludarabine, cyclophosphamide and low dose Total Body Irradiation with or without anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation, immunosuppressive cyclosporine and mycophenolate mofetil and post-transplant use of bone marrow-stimulating filgrastim.
intervention Names
Biological: anti-thymocyte globulin
Drug: cyclophosphamide
Drug: cyclosporine
Drug: fludarabine
Drug: mycophenolate mofetil
Procedure: stem cell transplantation
Radiation: total body irradiation
Drug: filgrastim
label
High Risk Patients
type
EXPERIMENTAL
description
Nonmyeloablative conditioning using fludarabine, cyclophosphamide and low dose Total Body Irradiation with or without anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation, immunosuppressive cyclosporine and mycophenolate mofetil and post-transplant use of bone marrow-stimulating filgrastim.
intervention Names
Biological: anti-thymocyte globulin
Drug: cyclophosphamide
Drug: cyclosporine
Drug: fludarabine
Drug: mycophenolate mofetil
Procedure: stem cell transplantation
Radiation: total body irradiation
Drug: filgrastim
label
Standard Risk Patients
type
EXPERIMENTAL

interventions

arm Group Labels
High Risk Patients
Standard Risk Patients
description
ATG dose is 15 mg/kg intravenous (IV) every 12 hours for 6 doses on days -6, -5, and -4. Those that should/will receive ATG in the preparative regimen: * Related donor recipients who have not had exposure to combination chemotherapy in the 6 months preceding transplant should * Unrelated donor recipients who have not had exposure to combination chemotherapy in the 3 months preceding transplant will * Unrelated donor recipients who have had only a single induction cycle for the treatment of ALL/AML or MDS or CML blast crisis should * Recipients with a prior autologous transplant in the year prior to second transplant do not require ATG.
name
anti-thymocyte globulin
other Names
ATG
type
BIOLOGICAL
arm Group Labels
High Risk Patients
Standard Risk Patients
description
Cyclophosphamide will be given in a two hour infusion, total dose 50 mg/kg on day -6.
name
cyclophosphamide
other Names
Cytoxan
type
DRUG
arm Group Labels
High Risk Patients
Standard Risk Patients
description
Patients will receive cyclosporine A (CSA) therapy beginning on day -3 maintaining a level of \>200. For adults the initial dose will be 2.5 mg/kg IV over 2 hours every 12 hours. For children \< 40 kg the initial dose will be 2.5 mg/kg IV over 2 hours every 8 hours. Patients will receive CSA until day +100.
name
cyclosporine
other Names
CSA
type
DRUG
arm Group Labels
High Risk Patients
Standard Risk Patients
description
Fludarabine 30 mg/m\^2/day intravenous (IV) on day -6 through day -2., total dose 150 mg/m\^2 for 5 days.
name
fludarabine
other Names
Fludara
type
DRUG
arm Group Labels
High Risk Patients
Standard Risk Patients
description
Mycophenolate mofetil (MMF) 1.5 gram twice a day (BID) or if \< 50 kg will be given 15 mg/kg orally(po) BID,beginning on day -3, and discontinue at day +30 or 7 days after engraftment (3 consecutive days of absolute neutrophil count (ANC) \> 0.5 x 109 /L).
name
mycophenolate mofetil
other Names
MMF
type
DRUG
arm Group Labels
High Risk Patients
Standard Risk Patients
description
On day 0, if related donor, stem cells are infused via central line. If unrelated donor, marrow/PBSC is infused after arrival and processing on day 0.
name
stem cell transplantation
other Names
peripheral blood stem cell transplantation
bone marrow transplant
type
PROCEDURE
arm Group Labels
High Risk Patients
Standard Risk Patients
description
The dose of TBI will be 200 cGy given in a single fraction on day -1.
name
total body irradiation
other Names
TBI
type
RADIATION
arm Group Labels
High Risk Patients
Standard Risk Patients
description
Patients with white blood cell (WBC) counts \< 2500 any time after stem cell infusion will be started on G-CSF support at Day +5 at a dose of 5 mcg/kg intravenously or subcutaneously (IV/SQ) daily rounded to vial size until absolute neutrophil count (ANC) \> 2500 for 2 consecutive days.
name
filgrastim
other Names
G-CSF
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 342
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Successful sustained engraftment is defined as primary neutrophil engraftment by day 42 and e90% donor cells at day 100, with or without DLI. Engraftment based on absolute neutrophil count of donor origin \> 0.5 x 10e9 /L for 3 days by day 42
measure
Neutrophil and Donor Cell Engraftment
time Frame
Day 42 and Day 100

secondary Outcomes

description
Safety by development of severe adverse events within 100 days of transplant
measure
Serious Adverse Events
time Frame
Day 100
description
\> 30% transplant related mortality at 100 days (non-relapse).
measure
Transplant Related Mortality
time Frame
Day 100
measure
Overall Survival
time Frame
1 year
description
Grade III-IV graft versus host disease
measure
Acute Graft-Versus-Host Disease
time Frame
Day 100

Full study description

brief Summary: RATIONALE: A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy, or that have become cancer. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclophosphamide and fludarabine together with total-body irradiation followed by cyclosporine and mycophenolate mofetil before the transplant may stop this from happening. PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy followed by cyclosporine and mycophenolate mofetil works in treating patients who are undergoing a donor stem cell transplant for hematologic cancer, metastatic breast cancer, or kidney cancer.
detailed Description: OBJECTIVES: * Determine if a nonmyeloablative regimen comprising cyclophosphamide, fludarabine, and radiotherapy followed by cyclosporine and mycophenolate mofetil provides a prompt and durable donor engraftment in patients with hematologic malignancies or kidney cancer who are undergoing allogeneic stem cell transplantation. * Determine the safety of this nonmyeloablative transplantation regimen in these patients. * Determine the risk of graft-versus-host-disease in patients treated with this regimen. * Determine the antineoplastic potency of nonmyeloablative stem cell transplantation in patients treated with this regimen. * Determine the effect of lower doses of daily fludarabine on treatment-related mortality (TRM) OUTLINE: Patients are stratified according to risk (standard vs high). * Preparative regimen\*: Patients receive cyclophosphamide intravenously (IV) over 2 hours on day -6 and fludarabine IV over 1 hour on days -6 to -2. Patients undergo total body irradiation on day -1. Some patients also receive anti-thymocyte globulin (ATG)\*\* IV every 12 hours on days -6 to -4. Patients who receive ATG\* include the following: * Related donor recipients who have not received combination chemotherapy within the past 6 months * Unrelated donor recipients who have not received combination chemotherapy within the past 3 months * Unrelated donor recipients who have received only 1 induction course for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or blastic phase chronic myelogenous leukemia (CML) NOTE: \*\*Patients who underwent prior autologous stem cell transplantation in the past year do not receive ATG. * Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo allogeneic PBSCT on day 0. * Graft-versus-host-disease prophylaxis: Patients receive cyclosporine IV over 2 hours beginning on day -3 and continuing until at least day 100. Patients also receive mycophenolate mofetil IV or orally twice daily on days -3 to 30. * Donor lymphocyte infusion (DLI): Patients without active GVHD but deteriorating donor chimerism may receive DLI IV over 2 hours. After completion of study treatment, patients are followed periodically for 2 years. PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.

Source references

references

citation
Warlick E, Ahn KW, Pedersen TL, Artz A, de Lima M, Pulsipher M, Akpek G, Aljurf M, Cahn JY, Cairo M, Chen YB, Cooper B, Deol A, Giralt S, Gupta V, Khoury HJ, Kohrt H, Lazarus HM, Lewis I, Olsson R, Pidala J, Savani BN, Seftel M, Socie G, Tallman M, Ustun C, Vij R, Vindelov L, Weisdorf D. Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era. Blood. 2012 Apr 26;119(17):4083-90. doi: 10.1182/blood-2012-02-409763. Epub 2012 Mar 9.
pmid
22408257
type
BACKGROUND
citation
Warlick ED, DeFor TE, Bejanyan N, Holtan S, MacMillan M, Blazar BR, Dusenbery K, Arora M, Bachanova V, Cooley S, Lazaryan A, McGlave P, Miller JS, Rashidi A, Slungaard A, Vercellotti G, Ustun C, Brunsein C, Weisdorf D. Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies: Expanded Analysis and Long-Term Follow-Up. Biol Blood Marrow Transplant. 2019 Jan;25(1):56-62. doi: 10.1016/j.bbmt.2018.07.038. Epub 2018 Aug 1.
pmid
30077015
type
BACKGROUND
citation
Bachanova V, Burke MJ, Yohe S, Cao Q, Sandhu K, Singleton TP, Brunstein CG, Wagner JE, Verneris MR, Weisdorf DJ. Unrelated cord blood transplantation in adult and pediatric acute lymphoblastic leukemia: effect of minimal residual disease on relapse and survival. Biol Blood Marrow Transplant. 2012 Jun;18(6):963-8. doi: 10.1016/j.bbmt.2012.02.012. Epub 2012 Mar 16.
pmid
22430088
type
DERIVED
citation
Bachanova V, Sandhu K, Yohe S, Cao Q, Burke MJ, Verneris MR, Weisdorf D. Allogeneic hematopoietic stem cell transplantation overcomes the adverse prognostic impact of CD20 expression in acute lymphoblastic leukemia. Blood. 2011 May 12;117(19):5261-3. doi: 10.1182/blood-2011-01-329573. Epub 2011 Mar 14.
pmid
21403127
type
DERIVED
citation
Bachanova V, Verneris MR, DeFor T, Brunstein CG, Weisdorf DJ. Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation. Blood. 2009 Mar 26;113(13):2902-5. doi: 10.1182/blood-2008-10-184093. Epub 2009 Jan 28.
pmid
19179301
type
DERIVED