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

NCT00572897 | Completed Phase 2 Results DMC

• 3 other identifiers: GCO 07-0548-00101P01CA108671-01A2MPD-RC 101
• Study Type: interventional
• Target: 66
• Locations: 4 countries
• Sites: 12

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.

Conditions

Myelofibrosis

Keywords

Myelofibrosis; Myeloproliferative disease; Stem Cell Transplant; Allogeneic Transplant; Conditioning Regimen; Reduced Intensity Regimen; Fludarabine; Melphalan; ATG

Outcome Measures

Primary Outcomes (1)

• The Primary Endpoint is Progression-free Survival.

  Number of participants alive at 2 years who are progression-free

  2 years

Secondary Outcomes (5)

• Response Outcomes

  180 days

• Overall Survival

  73 months

• Absolute Neutrophil Count (ANC)

  2 years

• PLT

  2 years

• Transplant-related Mortality

  2 years

Study Arms (1)

Fludarabine, Melphalan +/- ATG

EXPERIMENTAL

Fludarabine, Melphalan +/- ATG

Drug: Fludarabine, Melphalan +/- ATG

Interventions

Fludarabine, Melphalan +/- ATG DRUG

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 \[given over 4 hours\])

Fludarabine, Melphalan +/- ATG

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• John Mascarenhas: lead
• National Institutes of Health (NIH): collaborator
• Myeloproliferative Disorders-Research Consortium: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (12)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Johns Hopkins

Baltimore, Maryland, 21205, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Ohio State Univesity

Columbus, Ohio, 43210, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Princess Margaret Hospital

Toronto, Ontario, M5G2M9, Canada

Location

Ospedali Riuniti di Bergamo

Bergamo, Bergamo, 24128, Italy

Location

University of Florence

Florence, IL, 60302, Italy

Location

University of San Martino

San Martino, Italy

Location

Regionala etikprovningsnamnden Goteborg

Gothenburg, 60302, Sweden

Location

Related Publications (1)

• 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.

  PMID: 24963042 RESULT

MeSH Terms

Conditions

Primary Myelofibrosis; Myeloproliferative Disorders

Interventions

fludarabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Dr. Damiano Rondelli
• Organization: Univeristy of Illinois Hospital & Health Sciences System

drond@uic.edu

312-996-6179

Study Officials

• John Mascarenhas, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Giovanni Barosi, MD

  Myeloproliferative Disorders-Research Consortium

  STUDY CHAIR

• Damiano Rondelli, MD

  Myeloproliferative Disorders-Research Consortium

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 11, 2007
• First Posted: December 13, 2007
• Study Start: August 1, 2007
• Primary Completion: August 1, 2011
• Study Completion: June 15, 2015
• Last Updated: May 15, 2017
• Results First Posted: May 2, 2016

Record last verified: 2017-04

Locations

CA (1); SE (1); IT (3); US (7)