Stem Cell Transplantation for Hematological Malignancies - Full Text View

Purpose

This protocol using busulfan, cyclophosphamide and melphalan has been designed as conditioning therapy for patients receiving stem cell transplantation for acute leukemia or myelodysplastic syndrome (MDS). The hypothesis is that this new regimen will be well tolerated and will cure the patient.

Condition	Intervention	Phase
Leukemia, Lymphocytic, Acute AML MDS	Procedure: Stem Cell Transplant Drug: Busulfan Drug: Cyclophosphamide Drug: Melphalan Drug: G-CSF Drug: ATG	Phase 2 Phase 3

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Busulfan, Cyclophosphamide, and Melphalan Followed by Allogeneic Hematopoietic Cell Transplantation in Patients With Hematological Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia

Drug Information available for: Cyclophosphamide Busulfan Melphalan Melphalan hydrochloride Filgrastim Lenograstim Granulocyte colony-stimulating factor Antilymphocyte Serum

U.S. FDA Resources

Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:

Probability of Long-term Disease-free Survival (DFS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Number of participants with long-term disease free survival after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies.

Secondary Outcome Measures:

Probability of Engraftment [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Number of participants with engraftment after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies..
Incidence of Acute Graft-versus-host Disease (GVHD) [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: Yes ]
Number of participants with acute GVHD after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies.
Incidence Chronic Graft-versus-host Disease (GVHD) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Number of participants with chronic GVHD after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies.
Incidence of Regimen-related Toxicity 100 Days Post Transplant [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: Yes ]
Number of participants with regimen-related toxicity 100 days post transplant after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies.
Incidence of Relapse [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Number of patients with relapse after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies.

Enrollment:	11
Study Start Date:	June 2000
Study Completion Date:	October 2012
Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment Arm Patients treated with therapy plan consisting of Busulfan every 6 hours on days -7 through -4, Cyclophosphamide 60 mg/kg/day IV x 2 days, Melphalan 140 mg/m on day -1, antithymocyte globulin (ATG), G-CSF (granulocyte colony-stimulating factor) and stem cell transplantation on day 0.	Procedure: Stem Cell Transplant Certain cancers can be treated by giving patients stem cells that come from someone else. This is called a stem-cell transplant. As part of the transplant process, patients receive high doses of chemotherapy and/or radiation to treat their underlying disease, such as cancer. As one of its effects, this treatment also kills the healthy stem cells that are already in the marrow. The transplant provides new stem cells for the patient from a healthy donor; that replace the bone marrow and allow the blood counts to recover. Other Names: Bone Marrow Transplant umbilical cord transplant hematopoietic stem cell transplant Drug: Busulfan Prior to transplantation, subjects will receive BUSULFAN via the central venous line, four times a day for four days (days -7 through -4). Other Name: Busulfex, Myleran Drug: Cyclophosphamide Prior to stem cell transplantation, subjects will receive CYCLOPHOSPHAMIDE via the central venous line once a day for two days on days -3 and -2. Other Name: Cytoxan, Neosar Drug: Melphalan MELPHALAN will be given via the central venous line for one day, on day -1, prior to stem cell transplantation. Other Name: Alkeran Drug: G-CSF G-CSF is to be given daily IV beginning on day +1 until ANC 2.5 x 109/L. Other Name: granulocyte colony-stimulating factor, Filgrastim, Neupogen Drug: ATG ATG will be administered to umbilical cord blood recipients. Other Name: antithymocyte globulin

Arms

Assigned Interventions

Experimental: Treatment Arm

Patients treated with therapy plan consisting of Busulfan every 6 hours on days -7 through -4, Cyclophosphamide 60 mg/kg/day IV x 2 days, Melphalan 140 mg/m on day -1, antithymocyte globulin (ATG), G-CSF (granulocyte colony-stimulating factor) and stem cell transplantation on day 0.

Procedure: Stem Cell Transplant

Certain cancers can be treated by giving patients stem cells that come from someone else. This is called a stem-cell transplant. As part of the transplant process, patients receive high doses of chemotherapy and/or radiation to treat their underlying disease, such as cancer. As one of its effects, this treatment also kills the healthy stem cells that are already in the marrow. The transplant provides new stem cells for the patient from a healthy donor; that replace the bone marrow and allow the blood counts to recover.

Other Names:

Bone Marrow Transplant
umbilical cord transplant
hematopoietic stem cell transplant

Drug: Busulfan

Prior to transplantation, subjects will receive BUSULFAN via the central venous line, four times a day for four days (days -7 through -4).

Other Name: Busulfex, Myleran

Drug: Cyclophosphamide

Prior to stem cell transplantation, subjects will receive CYCLOPHOSPHAMIDE via the central venous line once a day for two days on days -3 and -2.

Other Name: Cytoxan, Neosar

Drug: Melphalan

MELPHALAN will be given via the central venous line for one day, on day -1, prior to stem cell transplantation.

Other Name: Alkeran

Drug: G-CSF

G-CSF is to be given daily IV beginning on day +1 until ANC 2.5 x 109/L.

Other Name: granulocyte colony-stimulating factor, Filgrastim, Neupogen

Drug: ATG

ATG will be administered to umbilical cord blood recipients.

Other Name: antithymocyte globulin

Detailed Description:

Subjects will be admitted to the bone marrow transplant unit and put in isolation to reduce exposure to infectious agents.

Prior to transplantation, they will receive BUSULFAN via the central venous line, four times a day for four days, CYCLOPHOSPHAMIDE via the central venous line once a day for two days, and MELPHALAN via the central venous line for one day. Busulfan, cyclophosphamide, and melphalan are given to destroy the subject's cancer. As well, these drugs will destroy their immune system to help ensure the new stem cells take and grow after transplantation.

On the day of transplantation, umbilical cord blood from the donor will be transfused via venous line. These new cells will replace the subject's bone marrow.

After transplantation, the subjects will receive Cyclosporin A and either MMF or MTX

Isolation will be continued until adequate numbers of cells are present in the blood to fight infection. Subjects will be discharged from the hospital when medically ready. They will be expected to return for follow-up to the blood and marrow transplant clinic at specific dates as determined by physicians.

Eligibility

Ages Eligible for Study:	up to 35 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must have a diagnosis of acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and currently be in complete remission.
Patients must be either:
- <18 years of age who are at least 6 months after initial hematopoietic cell transplant (HCT),
- 19-35 years of age and at least 18 months after initial HCT, or
- <35 years of age and have received sufficient radiation treatment to be ineligible for total body irradiation (TBI) containing preparative therapy
Adequate major organ function including:
- Cardiac: ejection fraction > or = 45%
- Renal: creatinine clearance > or = 40 mL/min
- Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites)
- Karnofsky performance status > or = 70% or Lansky score > or = 50%
Women of child bearing age must be using adequate birth control and have a negative pregnancy test.
Written informed consent.

Exclusion Criteria:

Eligible for TBI containing preparative regimen.
Active uncontrolled infection within one week of HCT.
Pregnant or lactating females.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00176839

Locations

United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

Principal Investigator:

Margaret MacMillan, MD

Masonic Cancer Center, University of Minnesota

More Information

No publications provided

Responsible Party:	Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT00176839 History of Changes
Other Study ID Numbers:	2000LS040, MT2000-12, 0005M52481
Study First Received:	September 12, 2005
Results First Received:	January 11, 2013
Last Updated:	March 12, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:

Stem Cell transplant
retransplant
hematological malignancies

Additional relevant MeSH terms:

Neoplasms
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Hematologic Diseases
Antilymphocyte Serum
Busulfan
Cyclophosphamide

Melphalan
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on May 23, 2013