Clinical trial NCT00572897: Study of Fludarabine Based Conditioning for Allogeneic Stem Cell Transplantation for Myelofibrosis
Official title: Study of Fludarabine Based Conditioning for Allogeneic Stem Cell Transplantation for Myelofibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelofibrosis
Keywords: Myelofibrosis
Myeloproliferative disease
Stem Cell Transplant
Allogeneic Transplant
Conditioning Regimen
Reduced Intensity Regimen
Fludarabine
Melphalan
ATG
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Myeloproliferative Disorders-Research Consortium
name: National Cancer Institute (NCI)
First posted: 2007-12-13
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Stem cell transplantation is used to treat may types of diseases. There a 2 types of transplants, conventional (very intense) and reduced intensity-non-myeloablative, also called mini-transplants.

This study proposes to use a conditioning regimen for allogeneic transplantation along with a reduced intensity transplant. Conditioning regiment is the name for the combination of chemotherapy drugs that is given to patients before receiving a transplantation of donor stem cells. It is hoped that the regimen designed for this study proves to be less toxic and has an equal or better anticancer effect than the regimens that are normally used. The regimen being used is a combination of two chemotherapy drugs, fludarabine and melphalan. This regimen has been studied in recipients of matched sibling transplants and in recipients of alternative donor stem cells in other hematologic malignancies. Those subjects, who receive stem cells from an unrelated donor, will also receive and additional drug called ATG or anti thymocyte globulin. ATG suppresses the immune system, thus reducing the chances for the recipient rejecting the transplant (graft).

The purpose of this study is to observe if reduced intensity transplants can be used to allow engraftment or "take" of the donor's bone marrow. Studies conducted in the past show this type of transplant is much less toxic than traditional bone marrow transplants. Reduced intensity transplants may be better tolerated by patients who may experience serious side effects from standard (very intense) stem cell transplant.

The study has been recently amended to follow all subjects for survival.

Detailed description: This study is designed as a single arm Phase II clinical trial in patients with myelofibrosis who are eligible for transplantation from a related donor or from an unrelated donor source. Patients will be accrued into two separate strata defined by donor type. Each of the two strata will be analyzed separately.

Patients will be followed yearly from time of enrollment into the study to assess clinical response and overall, progression and event free survival, as well as incidence and degree of acute and chronic GVHD. We will estimate cumulative survival and transplant related mortality in patients enrolled in each of the two strata.

Eligibility criteria: Inclusion Criteria:

* Patients with the following disease: Idiopathic myelofibrosis, or spent PV-, or ET-related myelofibrosis in chronic phase (\<20% blast cells in the bone marrow) with Lille score \>1 at any time, or platelet \<100K.
* Age 18-65 years.
* ECOG performance status \< 3.
* Life expectancy \>3 months.
* Adequate cardiac function, normal LVEF ≥ 45% by MUGA or echocardiogram and adequate pulmonary function DLCO ≥ 50% of predicted.
* Serum creatinine \< 1.1 x the upper limit of normal (ULN) or Creatinine Clearance \>50 ml/min.
* Serum bilirubin \< 2.0 mg/dl, SGPT \<2.5 x upper limit of normal
* No evidence of chronic active hepatitis or cirrhosis
* HIV-negative
* Patient is not pregnant
* Patient or guardian able to sign informed consent.
* Patients with \>20% myeloblasts in the blood or marrow, extramedullary blast cell proliferation or large foci of blasts in bone marrow biopsy specimens are not eligible.
* Pretransplant splenectomy: MMM patients with variable degrees of splenomegaly, or splenectomized, are eligible to be enrolled. Any decision of having a patient splenectomized prior to transplant will be made in each center prior to enrolling the patient in the study.
* Patients should be off treatment with investigational for at least 4 weeks and have recovered from all toxicities.

Exclusion Criteria:

* Pregnancy
* HIV positive
* \> 20% myeloblasts in the peripheral blood or bone marrow
* LVEF \< 45%
* DLCO \< 50% of predicted
* ECOG performance status ≥ 3
* Chronic active hepatitis or cirrhosis
* Chronic renal insufficiency

Primary outcomes:
measure: The Primary Endpoint is Progression-free Survival.
timeFrame: 2 years
Secondary outcomes:
measure: Response Outcomes
timeFrame: 180 days
measure: Overall Survival
timeFrame: 73 months
measure: Absolute Neutrophil Count (ANC)
timeFrame: 2 years
measure: PLT
timeFrame: 2 years
measure: Transplant-related Mortality
timeFrame: 2 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Columbus
country: United States
facility: Ohio State Univesity
state: Ohio
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Florence
country: Italy
facility: University of Florence
state: IL
city: Bergamo
country: Italy
facility: Ospedali Riuniti di Bergamo
city: San Martino
country: Italy
facility: University of San Martino
city: Goteborg
country: Sweden
facility: Regionala etikprovningsnamnden Goteborg
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: John Mascarenhas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Myeloproliferative Disorders-Research Consortium
name: Giovanni Barosi, MD
role: STUDY_CHAIR
affiliation: Myeloproliferative Disorders-Research Consortium
name: Damiano Rondelli, MD
role: STUDY_CHAIR
References:
citation: Rondelli D, Goldberg JD, Isola L, Price LS, Shore TB, Boyer M, Bacigalupo A, Rambaldi A, Scarano M, Klisovic RB, Gupta V, Andreasson B, Mascarenhas J, Wetzler M, Vannucchi AM, Prchal JT, Najfeld V, Orazi A, Weinberg RS, Miller C, Barosi G, Silverman LR, Prosperini G, Marchioli R, Hoffman R. MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. Blood. 2014 Aug 14;124(7):1183-91. doi: 10.1182/blood-2014-04-572545. Epub 2014 Jun 24.