Busulfan/Clofarabine + Allogeneic Stem Cell Transplantation

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Yi-Bin A. Chen, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01643668
First received: June 12, 2012
Last updated: September 9, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndrome
Drug: Busulfan
Drug: Clofarabine
Procedure: Allogeneic Stem Cell Infusion
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Reduced Intensity Conditioning With Busulfan/Clofarabine Followed by Allogeneic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Assessment of donor stem cell engraftment: ANC count [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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

  • Assessment of donor stem cell engraftment: Platelet count [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Platelets at least 20,000/uL on 3 consecutive measurements without transfusional support prior to day +100 after BuClo RIC HSCT


Secondary Outcome Measures:
  • Assessment of non-relapse mortality [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assessment of non-relapse mortality (NRM) at day 100 and 1 year after BuClo RIC SCT

  • Assessment of progression-free and overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assess 1-year and 2-year progression-free and overall survival

  • Assess incidence and severity of GVHD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assess the incidence and severity of grades 2-4 and grades 3-4 acute graft-versus-host disease (GVHD) developing by day 200

  • Assess incidence and severity of chronic GVHD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assess the incidence and severity of chronic GVHD

  • Assess incidence of hepatic veno-occlusive disease [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assess the incidence of hepatic veno-occlusive disease (VOD)

  • Assess toxicity of BuClo RIC regimen [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Assess toxicity of BuClo RIC regimen

  • Assess infection-related complications [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assess infection-related complications


Estimated Enrollment: 34
Study Start Date: July 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm
BuClo RIC SCT
Drug: Busulfan
Busulfan as part of reduced intensity conditioning prior to allogeneic stem cell transplantation
Drug: 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

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01643668

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Yi-Bin Chen, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Yi-Bin A. Chen, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01643668     History of Changes
Other Study ID Numbers: 12-128
Study First Received: June 12, 2012
Last Updated: September 9, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Busulfan
Clofarabine
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on October 01, 2014