Study of Fludarabine Based Conditioning for Allogeneic Stem Cell Transplantation for Myelofibrosis

Phase 2

Completed

Conditions: Myelofibrosis

Interventions: Drug: Fludarabine, Melphalan +/- ATG

Registration Number: NCT00572897

Lead Sponsor: John Mascarenhas

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 66

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fludarabine, Melphalan +/- ATG	Fludarabine, Melphalan +/- ATG	Fludarabine, Melphalan +/- ATG

Primary Outcome Measures

Name	Time	Method
The Primary Endpoint is Progression-free Survival.	2 years	Number of participants alive at 2 years who are progression-free

Secondary Outcome Measures

Name	Time	Method
Response Outcomes	180 days	assessed according to the IWG Criteria
Overall Survival	73 months	The number of patients alive at last follow-up.
PLT	2 years	Patients with PLT ≥20 × 109/L
Absolute Neutrophil Count (ANC)	2 years	Patients with ANC ≥0.5 × 10\^9/L
Transplant-related Mortality	2 years	Transplant-related Mortality including Graft-versus-host disease (GVHD)

Trial Locations

Locations (12): University of Florence
🇮🇹
Florence, IL, Italy
Ohio State Univesity
🇺🇸
Columbus, Ohio, United States
University of Utah
🇺🇸
Salt Lake City, Utah, United States
Princess Margaret Hospital
🇨🇦
Toronto, Ontario, Canada
Ospedali Riuniti di Bergamo
🇮🇹
Bergamo, Italy
Regionala etikprovningsnamnden Goteborg
🇸🇪
Goteborg, Sweden
University of San Martino
🇮🇹
San Martino, Italy
University of Illinois at Chicago
🇺🇸
Chicago, Illinois, United States
Johns Hopkins
🇺🇸
Baltimore, Maryland, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸
New York, New York, United States
Weill Cornell Medical College
🇺🇸
New York, New York, United States