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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Myeloproliferative Disorders-Research Consortium
Information provided by (Responsible Party):
John Mascarenhas, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT00572897
First received: December 11, 2007
Last updated: October 23, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention
Myelofibrosis
Drug: Fludarabine, Melphalan +/- ATG

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study of Fludarabine Based Conditioning for Allogeneic Stem Cell Transplantation for Myelofibrosis

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • The primary endpoint is progression-free survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Secondary endpoints will include the proportion of patients "cured" (resolution of splenomegaly and normalization of blood counts), duration of cure, rates of transplant-related mortality, and overall survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 66
Study Start Date: August 2007
Estimated Study Completion Date: August 2020
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fludarabine, Melphalan +/- ATG
Fludarabine, Melphalan +/- ATG
Drug: Fludarabine, Melphalan +/- ATG

Conditioning regimen for Allogenic Stem Cell Transplant:

Related Donor Fludarabine days -6 to -2 (30mg/m2 IVPB over 30 minutes daily) Melphalan days -3 to -2 (70mg/m2 IVPB over 30 minutes daily)

Unrelated Donor Fludarabine days -6 to -2 (30mg/m2 IVPB over 30 minutes daily) Melphalan days -3 to -2 (70mg/m2 IVPB over 30 minutes daily) ATG (Thymoglobulin®) days -3 to -1 (0.5 mg/kg IV on day -3 [given over 6 hours], and 2 mg/kg on days -2 and -1 [given over 4 hours])


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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00572897

Locations
United States, Illinois
University of Illinois at Chicago
Chicago, Illinois, United States, 60612
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21205
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Weill Cornell Medical College
New York, New York, United States, 10065
United States, Ohio
Ohio State Univesity
Columbus, Ohio, United States, 43210
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G2M9
Italy
University of Florence
Florence, IL, Italy, 60302
Ospedali Riuniti di Bergamo
Bergamo, Italy, 24128
University of San Martino
San Martino, Italy
Sweden
Regionala etikprovningsnamnden Goteborg
Goteborg, Sweden, 60302
Sponsors and Collaborators
John Mascarenhas
Myeloproliferative Disorders-Research Consortium
Investigators
Principal Investigator: John Mascarenhas, MD Mount Sinai School of Medicine
Study Chair: Giovanni Barosi, MD Myeloproliferative Disorders-Research Consortium
Study Chair: Damiano Rondelli, MD Myeloproliferative Disorders-Research Consortium
  More Information

No publications provided

Responsible Party: John Mascarenhas, Assistant Professor, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT00572897     History of Changes
Other Study ID Numbers: GCO 07-0548-00101, P01 Ca 108671-01A2, MPD-RC 101
Study First Received: December 11, 2007
Last Updated: October 23, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Mount Sinai School of Medicine:
Myelofibrosis
Myeloproliferative disease
Stem Cell Transplant
Allogeneic Transplant
Conditioning Regimen
Reduced Intensity Regimen
Fludarabine
Melphalan
ATG

Additional relevant MeSH terms:
Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Melphalan
Fludarabine
Fludarabine monophosphate
Vidarabine
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 26, 2014