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

NCT ID: NCT00572897

Last Updated: 2017-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2015-06-15

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.

Conditions

Myelofibrosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fludarabine, Melphalan +/- ATG

Fludarabine, Melphalan +/- ATG

Group Type: EXPERIMENTAL

Fludarabine, Melphalan +/- ATG

Intervention Type: 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])

Interventions

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])

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Myeloproliferative Disorders-Research Consortium

NETWORK

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

John Mascarenhas

OTHER

Sponsor Role: lead

Responsible Party

John Mascarenhas

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

John Mascarenhas, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Giovanni Barosi, MD

Role: STUDY_CHAIR

Myeloproliferative Disorders-Research Consortium

Damiano Rondelli, MD

Role: STUDY_CHAIR

Myeloproliferative Disorders-Research Consortium

Locations

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

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, Bergamo, Italy

University of Florence

Florence, IL, Italy

University of San Martino

San Martino, , Italy

Regionala etikprovningsnamnden Goteborg

Gothenburg, , Sweden

Countries

United States; Canada; Italy; Sweden

References

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.

Reference Type: RESULT

PMID: 24963042 (View on PubMed)

Other Identifiers

P01CA108671-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MPD-RC 101

Identifier Type: OTHER

Identifier Source: secondary_id

GCO 07-0548-00101

Identifier Type: -

Identifier Source: org_study_id