Busulfan/Clofarabine + Allogeneic Stem Cell Transplantation

NCT01643668 | Completed Phase 2 Results DMC

• 1 other identifier: 12-128
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Assessment of Donor Stem Cell Engraftment: ANC Count

  Patients are considered to have achieved donor cell engraftment if they have an absolute neutrophil count (ANC) of at least 500 cells/uL of blood for 3 consecutive measurements 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

  1, 2, 3, and 4 weeks after transplantation

• Donor Stem Cell Engraftment: Platelet Count

  Platelet recovery was defined as having a platelet count of at least 20,000 platelets/uL of blood on 2 consecutive measurements without transfusional support prior to day +100 after BuClo RIC HSCT.

  1, 2, 3, 4, 8, and 14 weeks post transplant

Secondary Outcomes (7)

• Cumulative Incidence of Non-relapse Mortality

  100 days, 1 year

• Progression-Free and Overall Survival

  1 year, 2 years

• Cumulative Incidence and Severity of Acute GVHD Within 100 Days Post Transplant

  100 days

• Cumulative Incidence of Chronic GVHD at One Year

  1 year

• Incidence of Hepatic Veno-occlusive Disease

  2 years

Study Arms (1)

BuClo RIC + SCT

EXPERIMENTAL

Busulfan and Clofarabine (BuClo) reduced intensity conditioning (RIC) followed by allogeneic stem cell Transplantation (SCT)

Drug: Busulfan; Drug: Clofarabine; Procedure: Allogeneic Stem Cell Infusion

Interventions

Busulfan DRUG

Busulfan as part of reduced intensity conditioning prior to allogeneic stem cell transplantation

BuClo RIC + SCT

Clofarabine DRUG

Clofarabine as part of reduced intensity conditioning prior to allogeneic stem cell transplantation

BuClo RIC + SCT

Allogeneic Stem Cell Infusion PROCEDURE

Allogeneic stem cell transplantation after reduced intensity conditioning with busulfan / clofarabine chemotherapy

BuClo RIC + SCT

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes

Interventions

Busulfan; Clofarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Results Point of Contact

• Title: Yi-Bin Chen, MD
• Organization: Massachusetts General Hospital

YCHEN6@PARTNERS.ORG

617-726-0187

Study Officials

• Yi-Bin Chen, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: June 12, 2012
• First Posted: July 18, 2012
• Study Start: July 1, 2012
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: July 13, 2017
• Results First Posted: July 13, 2017

Record last verified: 2017-06

Locations

US (3)