Busulfan Plus Clofarabine Followed by Allogeneic Hematopoietic Stem Cell Transplantation

Study Description

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Brief Summary:

The goal of this clinical research study is to test the safety of giving clofarabine in combination with busulfan, followed by an allogeneic (from a donor) stem cell transplant, in patients with advanced leukemia or lymphoma.

Condition or disease	Intervention/treatment	Phase
Leukemia; Lymphoma; Allogeneic Haematopoietic Stem Cell Transplantation; Acute Lymphoblastic Leukemia	Drug: Busulfan; Drug: Clofarabine; Drug: Thymoglobulin; Procedure: Stem Cell Transplant	Phase 2

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	120 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Busulfan Plus Clofarabine Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Acute Lymphoblastic Leukemia or Lymphoma, or Biphenotypic Leukemia
Study Start Date :	October 2009
Actual Primary Completion Date :	May 2016
Actual Study Completion Date :	May 2016

Arms and Interventions

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Arm

Intervention/treatment

Experimental: Busulfan + Clofarabine + Stem Cell Transplant; Busulfan test dose 32 mg/m^2 by vein over 45 minutes on Day -8; following doses on Days -6 to -3 derived from pharmacokinetic (PK) testing done up to 11 times over 11 hours after test dose. Clofarabine 40 mg/m^2 by vein over 1 hour daily Day -6 through Day -3. Thymoglobulin 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1; only patients with HLA nonidentical or unrelated donors. Stem cell infusion on Day 0.

Drug: Busulfan; Test Dose 32 mg/m^2 by vein over 45 minutes on Day -8; following doses on Days -6 to -3 derived from pharmacokinetic (PK) testing done up to 11 times over 11 hours after test dose.; Other Names: Busulfex; Myleran Drug: Clofarabine; 40 mg/m^2 by vein over 1 hour daily Day -6 through Day -3; Other Names: Clolar; Clofarex Drug: Thymoglobulin; 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1; only patients with HLA nonidentical or unrelated donors; Other Names: Anti-thymocyte globulin; ATG Procedure: Stem Cell Transplant; Stem cell infusion on Day 0.; Other Names: Allogeneic hematopoietic cell transplant; HCT

Outcome Measures

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Primary Outcome Measures :

1. Treatment-Related Mortality (TRM) [ Time Frame: Baseline and at day 100 of treatment ]
   For TRM at day 100, Bayesian method of Thall, Simon, and Estey used to perform interim monitoring. Rates of 100-day progression-free survival (PFS) and TRM estimated separately by cohort and provided with 95% credible intervals.

Eligibility Criteria

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Ages Eligible for Study:	up to 65 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Patients with biopsy-proven acute lymphoblastic leukemia, acute lymphoblastic lymphoma, or acute biphenotypic leukemia in remission or relapse.
2. Adequate renal function, as defined by estimated serum creatinine clearance >60 ml/min.
3. Bilirubin equal or less than 1.5 (unless Gilbert's Syndrome), serum glutamate pyruvate transaminase (SGPT) <3 X upper limit of normal and alkaline phosphatase <2 X upper limit of normal.
4. Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusion capacity of lung for carbon monoxide (DLCO) at least 45% of expected corrected for hemoglobin. Children unable to perform pulmonary functions must have an oxygen saturation greater than 92% at room air.
5. Adequate cardiac function with left ventricular ejection fraction at least 45% on appropriate medical therapy. No uncontrolled arrhythmias or symptomatic cardiac disease.
6. Zubrod performance status <2 or Lansky/Karnofsky PS equal or greater to 70%.
7. Patients must have a related, genotypically HLA identical donor, or they must have a unrelated donor who is 8/8 HLA match by high resolution typing.
8. Patient or patient's legal representative, parent(s) or guardian should provide written informed consent. Assent of a minor if participant's age is at least seven and less than eighteen years.
9. Negative Beta Human Chorionic Gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months and no previous surgical sterilization.

Exclusion Criteria:

1. Patients with unresolved grade >2 non-hematologic toxicity from previous therapy. Patients with grade 2 toxicity will be eligible at the discretion of the PI.
2. Patients with active central nervous system (CNS) disease.
3. Evidence of acute or chronic active hepatitis or cirrhosis.
4. Uncontrolled infection, including HIV, HTLV-1, hepatitis B or hepatitis C viremia.
5. Patients greater than 65 years-old.
6. Prior autologous or allogeneic hematopoietic stem cell transplant.

Contacts and Locations

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Locations

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Study Chair:	Partow Kebriaei, MD	M.D. Anderson Cancer Center

More Information

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Additional Information:

University of Texas MD Anderson Cancer Center Website 

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00990249 History of Changes
Other Study ID Numbers:	2009-0209; NCI-2012-01270 ( Registry Identifier: NCI CTRP )
First Posted:	October 6, 2009
Last Update Posted:	May 12, 2016
Last Verified:	May 2016

Keywords provided by M.D. Anderson Cancer Center:

Acute Lymphoblastic Leukemia; ALL; Acute lymphoblastic lymphoma; acute biphenotypic leukemia; Allogeneic hematopoietic cell transplantation; HCT; Stem Cell Transplant; Treatment-related mortality; Tyrosine kinase inhibitors	TKI; Busulfan; Busulfex; Myleran; Clofarabine; Clolar; Clofarex; Gleevec; Imatinib Mesylate

Additional relevant MeSH terms:

Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Busulfan; Thymoglobulin	Antilymphocyte Serum; Clofarabine; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents, Alkylating; Antineoplastic Agents; Myeloablative Agonists; Antimetabolites, Antineoplastic; Antimetabolites