Busulfan/Clofarabine + Allogeneic Stem Cell Transplantation

Acute Myeloid Leukemia Clinical Trial

Official title:

Phase II Study of Reduced Intensity Conditioning With Busulfan/Clofarabine Followed by Allogeneic Stem Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01643668
• Other study ID #: 12-128
• Status: Completed
• Phase: Phase 2
• First received: June 12, 2012
• Last updated: March 21, 2017
• Start date: July 2012
• Est. completion date: August 2016

Study information

• Verified date: March 2017
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research is a phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational intervention to learn whether it works in treating a specific cancer. "Investigational" means that the study intervention is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not yet approved this study intervention for your type of cancer.

All participants on this study are treated in an identical manner. The investigators are doing this study because there continues to be a significant risk of relapse of disease after reduced intensity transplantation. In studies which have compared transplants using high-doses of chemotherapy and/or radiation versus reduced intensity transplants, patients undergoing reduced intensity transplants appear to have higher rates of relapse, but lower rates of toxicity and complication. This study attempts to utilize clofarabine, a newer chemotherapy agent shown to be quite active in AML, ALL, and MDS, to increase the anti-tumor effects of the conditioning regimen without accumulating unacceptable toxicity.

The reduced intensity allogeneic stem cell transplantation procedure involves giving you chemotherapy in relatively less intense doses to suppress your immune system. This is followed by an infusion of healthy blood stem cells from a matched related donor or a matched unrelated volunteer donor. It is hoped that these donor cells can eventually then attack any cancer cells which remain.

In this research study, the investigators are looking to see how well this new combination of busulfan and clofarabine works in reduced intensity allogeneic stem cell transplantation. By "works" the investigators mean to analyze safety, ability of donor cells to engraft (take hold), as well as measures of complications including toxicity, infections, graft-vs-host disease (GVHD), and relapse.

Description:

You will start the conditioning regimen, which is also called the preparative regimen. Conditioning is done to kill more cancer cells which may remain as well as prepare your body for transplant. You will receive the conditioning drugs into a vein. The conditioning regimen consists of the following drugs: Busulfan and Clofarabine.

While you are in the hospital you will have regular physical exams and you will be asked specific questions about any problems that you might be having. You will also have blood tests every day to look at how your bone marrow is recovering, to give possible transfusional support, and how to see how your liver and kidneys are functioning.

You will receive the following drugs before and after the allogeneic stem cell transplant:

Neupogen (G-CSF) injections, drugs to prevent infections, Tacrolimus to prevent GVHD and Methotrexate.

You will have routine and regular follow-up in the transplant clinic after discharge from the hospital. The following will be performed at each visit:

Physical exam to monitor your health and check for signs of GVHD, infections and any side effects you may be having; Blood draw for routine blood tests to measure your blood cell count and chemistry; Blood tests to see if the transplanted stem cells are being accepted and are growing in the body (engraftment); Bone marrow biopsy to see the status of the underlying disease (to be done around 100 days after the stem cell transplant).

You will be asked to return to the clinic, at a minimum, for follow-up visits at 6 months, 9 months, 12 months, 18 months and 24 months after your stem cell transplant.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Must have well-matched adult donor willing to donate peripheral blood stem cells with well-matched defined as 8/8 matched related or unrelated donor

• Adequate organ functioning

Exclusion Criteria:

• Pregnant or breastfeeding

• Psychiatric disease severely impairing the compliance of the patient to participate in the study and/or give informed consent

• Evidence of prior exposure to HIV or HCV

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

Drug:
• Busulfan
Busulfan as part of reduced intensity conditioning prior to allogeneic stem cell transplantation
• Clofarabine
Clofarabine as part of reduced intensity conditioning prior to allogeneic stem cell transplantation

Procedure:
• Allogeneic Stem Cell Infusion
Allogeneic stem cell transplantation after reduced intensity conditioning with busulfan / clofarabine chemotherapy

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of donor stem cell engraftment: ANC count	ANC at least 500/uL and at least 75% of hematopoietic elements are donor-derived as determined by chimerism assays from peripheral blood prior to day +40 after Busulfan/Clofarabine (BuClo) reduced intensity allogeneic stem cell transplantation	2 years
Primary	Assessment of donor stem cell engraftment: Platelet count	Platelets at least 20,000/uL on 3 consecutive measurements without transfusional support prior to day +100 after BuClo RIC HSCT	2 years
Secondary	Assessment of non-relapse mortality	Assessment of non-relapse mortality (NRM) at day 100 and 1 year after BuClo RIC SCT	2 years
Secondary	Assessment of progression-free and overall survival	Assess 1-year and 2-year progression-free and overall survival	2 years
Secondary	Assess incidence and severity of GVHD	Assess the incidence and severity of grades 2-4 and grades 3-4 acute graft-versus-host disease (GVHD) developing by day 200	2 years
Secondary	Assess incidence and severity of chronic GVHD	Assess the incidence and severity of chronic GVHD	2 years
Secondary	Assess incidence of hepatic veno-occlusive disease	Assess the incidence of hepatic veno-occlusive disease (VOD)	2 years
Secondary	Assess toxicity of BuClo RIC regimen	Assess toxicity of BuClo RIC regimen	2 years
Secondary	Assess infection-related complications	Assess infection-related complications	2 years