Clinical trial NCT00438958: Sibling Donor Peripheral Stem Cell Transplant or Sibling Donor Bone Marrow Transplant in Treating Patients With Hematologic Cancers or Other Diseases
Official title: A Randomized Multicentre Study Comparing G-CSF Mobilized Peripheral Blood and G-CSF Stimulated Bone Marrow in Patients Undergoing Matched Sibling Transplantation for Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Myeloproliferative Disorders
Graft Versus Host Disease
Leukemia
Lymphoma
Myelodysplastic Syndromes
Secondary Myelofibrosis
Keywords: graft versus host disease
adult acute myeloid leukemia in remission
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
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)
accelerated phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
refractory anemia with ringed sideroblasts
refractory anemia
chronic myelomonocytic leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
refractory chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
primary myelofibrosis
secondary myelofibrosis
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent mycosis fungoides/Sezary syndrome
recurrent small lymphocytic lymphoma
splenic marginal zone lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult Hodgkin lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III small lymphocytic lymphoma
stage IV adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult Hodgkin lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage IV small lymphocytic lymphoma
Waldenström macroglobulinemia
secondary acute myeloid leukemia
childhood myelodysplastic syndromes
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-02-22
Enrollment: 230
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Giving chemotherapy before a donor peripheral stem cell transplant or bone marrow transplant using stem cells from a brother or sister that closely match the patient's stem cells, helps stop the growth of cancer or abnormal cells. It also helps 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 or abnormal 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 colony-stimulating factors, such as G-CSF, to the donor helps the stem cells move from the bone marrow to the blood so they can be collected and stored. Giving methotrexate and cyclosporine before and after transplant may stop this from happening. It is not yet known whether a donor peripheral stem cell transplant is more effective than a donor bone marrow transplant in treating hematologic cancers or other diseases.

PURPOSE: This randomized phase III trial is studying filgrastim-mobilized sibling donor peripheral stem cell transplant to see how well it works compared with sibling donor bone marrow transplant in treating patients with hematologic cancers or other diseases.

Detailed description: OBJECTIVES:

Primary

* Compare the time to treatment failure in patients with hematologic malignancies or other diseases treated with filgrastim (G-CSF)-mobilized matched-sibling donor peripheral blood stem cell transplantation vs G-CSF-stimulated matched-sibling donor bone marrow transplantation.

Secondary

* Compare the hematological recovery and overall survival of patients treated with these regimens.
* Compare the quality of life, in terms of extensive graft-versus-host disease (GVHD), in patients treated with these regimens.
* Compare the economic impact associated with these treatment regimens.

Tertiary

* Compare the incidence and severity of acute GVHD in patients treated with these regimens.
* Compare organ involvement, symptomatology, and functional impact of chronic GVHD in patients treated with these regimens.
* Compare disease-free survival of patients treated with these regimens.
* Compare donor quality of life.
* Compare cost analysis, from a societal perspective, of these treatment regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to treatment center, disease (chronic myelogenous leukemia vs acute myeloid leukemia vs myelodysplastic syndromes vs other hematologic malignancy), disease stage (early disease vs late disease), and conditioning regimen (busulfan and cyclophosphamide vs cyclophosphamide and total body irradiation vs other).

* Myeloablative conditioning regimen: Patients receive a myeloablative conditioning regimen that has been approved by the clinical chair.
* Stem cell transplantation (SCT): Patients are randomized to 1 of 2 SCT arms.

  * Arm I: Patients undergo sibling donor filgrastim (G-CSF)-mobilized peripheral blood SCT on day 0.
  * Arm II: Patients undergo sibling donor G-CSF- mobilized bone marrow transplantation on day 0.
* Graft-verus-host disease (GVHD) treatment: Patients receive methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV (or orally) every 12 hours beginning on day -2 and continuing until day 100.

Quality of life is assessed at baseline and at 1 and 3 years post-transplantation.

After completion of study therapy, patients are followed periodically for at least 4 years.

PROJECTED ACCRUAL: A total of 230 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of one of the following hematologic malignancies:

  * Acute myeloid leukemia in first complete remission or second complete remission
  * Chronic myeloid leukemia in chronic or accelerated phase
  * Myelodysplasia, including any of the following:

    * Refractory anemia (RA)
    * RA with ringed sideroblasts
    * RA with excess blasts (RAEB) I
    * RAEB in transformation
    * Chronic myelomonocytic leukemia
  * Other hematologic malignancy for which sibling donor stem cell transplantation with a myeloablative conditioning regimen is appropriate, including any of the following:

    * Indolent non-Hodgkin's lymphoma (NHL)
    * Aggressive NHL
    * Chronic lymphocytic leukemia
    * Hodgkin's lymphoma
    * Myelofibrosis
    * Hematologic malignancy not otherwise specified
* HLA-matched sibling donor available meeting all of the following criteria:

  * 6/6 HLA match

    * HLA typing performed by serologic or DNA methodology for A and B and by DNA methodology for DRB1 (intermediate resolution)
  * Not identical twin with patient

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No cognitive, linguistic, or emotional difficulty that would preclude participation in the quality-of-life component of the study
* Able to communicate in English or French
* No HIV antibody positivity

PRIOR CONCURRENT THERAPY:

* Not specified

Primary outcomes:
measure: Time to treatment failure (extensive chronic graft-versus-host disease [GVHD], relapse, death)
Secondary outcomes:
measure: Time to neutrophil recovery
measure: Primary graft failure
measure: Overall survival
measure: Quality of life
measure: Time to acute GVHD
measure: Time to chronic GVHD
measure: Chronic GVHD details
measure: Cost
measure: Detailed donor and patient self-reported outcomes
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Adelaide
country: Australia
facility: Institute of Medical and Veterinary Science
state: South Australia
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Vancouver
country: Canada
facility: Vancouver Hospital and Health Science Center
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: Cancer Care Nova Scotia
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster Children's Hospital at Hamilton Health Sciences
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Montreal
country: Canada
facility: Royal Victoria Hospital - Montreal
state: Quebec
city: Quebec City
country: Canada
facility: Hopital de L'Enfant Jesus
state: Quebec
city: Quebec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
state: Quebec
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital and Research Center
Study officials:
affiliation: Cancer Care Nova Scotia
name: Stephen Couban, MD
role: STUDY_CHAIR
affiliation: Princess Margaret Hospital, Canada
name: Jeffrey H. Lipton, MD, PhD
References:
citation: Kariminia A, Ivison S, Ng B, Rozmus J, Sung S, Varshney A, Aljurf M, Lachance S, Walker I, Toze C, Lipton J, Lee SJ, Szer J, Doocey R, Lewis I, Smith C, Chaudhri N, Levings MK, Broady R, Devins G, Szwajcer D, Foley R, Mostafavi S, Pavletic S, Wall DA, Couban S, Panzarella T, Schultz KR. CD56bright natural killer regulatory cells in filgrastim primed donor blood or marrow products regulate chronic graft-versus-host disease: the Canadian Blood and Marrow Transplant Group randomized 0601 study results. Haematologica. 2017 Nov;102(11):1936-1946. doi: 10.3324/haematol.2017.170928. Epub 2017 Sep 21.