Allogeneic Transplantation Using Timed Sequential Busulfan and Fludarabine Conditioning

NCT01572662 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2011-0958NCI-2012-00573
• Study Type: interventional
• Target: 201
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if giving busulfan and fludarabine before a stem cell transplant can help control the disease better than the standard method in patients with leukemia, lymphoma, multiple myeloma, MDS, or MPD. In this study, 2 doses of busulfan will be given 2 weeks before a stem cell transplant followed by 4 doses of busulfan and fludarabine during the week before the stem cell transplant, rather than the standard method of giving 4 doses of busulfan and fludarabine only during the week before the stem cell transplant. The safety of this combination therapy will also be studied. Busulfan is designed to kill cancer cells by binding to DNA (the genetic material of cells), which may cause cancer cells to die. Busulfan is commonly used in stem cell transplants. Fludarabine is designed to interfere with the DNA of cancer cells, which may cause the cancer cells to die.

Conditions

Leukemia; Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic Lymphocytic Leukemia; Myeloproliferative Diseases; Non-Hodgkins Lymphoma; Hodgkins Lymphoma; Multiple Myeloma; Myelodysplastic Syndrome

Keywords

Leukemia; Acute myeloid leukemia; Acute lymphocytic leukemia; Chronic myeloid leukemia; Chronic lymphocytic leukemia; Myeloproliferative Diseases; Non-Hodgkins Lymphoma; Hodgkins lymphoma; Multiple myeloma; Myelodysplastic syndrome; MDS; Fludarabine monophosphate; Fludarabine phosphate; Fludara; Busulfan; Busulfex; Myleran; Tacrolimus; Prograf; Methotrexate; G-CSF; Filgrastim; Neupogen; Stem cell transplant; Allogeneic Transplantation

Outcome Measures

Primary Outcomes (1)

• Non-Relapse Mortality Rate (NRM)

  Number of participants expired within the first 100 days after transplant not due to relapsed disease.

  100 days

Secondary Outcomes (2)

• Overall Survival

  Up to 1 year post-transplant

• Overall Survival

  Up to 3 years post-transplant

Study Arms (1)

Fludarabine + Busulfan

EXPERIMENTAL

Fludarabine administered by vein at dose of 40 mg/m2 in 100 ml of normal saline (NS) on Days -6 through -3. First two doses of Busulfan, 80 mg/m2 administered as an outpatient or as an inpatient to facilitate for this pharmacokinetically directed therapy. Busulfan is administered at the dose calculated to achieve a total (including first two doses delivered on day -13 and -12) systemic exposure of 20,000 ± 12% µMol-min based on the pharmacokinetic studies.

Drug: Fludarabine monophosphate; Drug: Busulfan; Procedure: Stem Cell Infusion; Drug: Tacrolimus; Drug: Methotrexate; Drug: G-CSF

Interventions

Fludarabine monophosphate DRUG

40 mg/m2 by vein on Days -6 through -3.

Also known as: Fludarabine Phosphate, Fludara

Fludarabine + Busulfan

Busulfan DRUG

First two doses of Busulfan, 80 mg/m2 administered as an outpatient or as an inpatient to facilitate for this pharmacokinetically directed therapy. Busulfan is administered at the dose calculated to achieve a total (including first two doses delivered on day -13 and -12) systemic exposure of 20,000 ± 12% µMol-min based on the pharmacokinetic studies.

Also known as: Busulfex, Myleran

Fludarabine + Busulfan

Stem Cell Infusion PROCEDURE

Fresh or cryopreserved bone marrow or peripheral blood progenitor cells infused on Day 0.

Fludarabine + Busulfan

Tacrolimus DRUG

Starting dose of 0.015 mg/kg (ideal body weight) as 24 hour continuous infusion daily adjusted to achieve therapeutic level of 5-15 ng/ml. Tacrolimus changed to oral dosing when tolerated and can be tapered off after day +90 if no graft versus host disease (GVHD) present.

Also known as: Prograf

Fludarabine + Busulfan

Methotrexate DRUG

5 mg/m2 by vein on Days 1, 3, 6 and 11 post transplant.

Fludarabine + Busulfan

G-CSF DRUG

5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is \> 500 \* 10/L for 3 consecutive days.

Also known as: Filgrastim, Neupogen

Fludarabine + Busulfan

Eligibility Criteria

• Age: 5 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with high-risk hematologic malignancies with anticipated poor prognosis with non transplant therapy, including those in remission or with induction failure and after treated or untreated relapse. Diagnoses to be included a) Acute myeloid leukemia; b) Acute lymphocytic leukemia; c) Chronic myeloid leukemia; d) Chronic lymphocytic leukemia; e) Myelodysplastic syndrome; f) Myeloproliferative syndromes; g) Non-Hodgkins lymphoma; h) Hodgkins Lymphoma; i) Multiple myeloma.
• Patients must have a histocompatible stem cell donor. An HLA-identical related donor or a 8/8 matched unrelated donor.
• Age 5 to 75 years old.
• Performance score of \>/= 70 by Karnofsky/Lansky or PS 0 to 1 (ECOG \</=1).
• Left ventricular ejection fraction at least 40%.
• Adequate pulmonary function with FEV1, FVC and DLCO \>/=50% of expected corrected for hemoglobin and/or volume. Children unable to perform pulmonary function tests (e.g., less than 7 years old) pulse oximetry of \>/= 92% on room air
• Creatinine clearance (calculated creatinine clearance is permitted) should be \>40 ml/min.
• Bilirubin \</= 2 x the upper limit of normal (except Gilbert's Syndrome). SGPT (ALT) \< 200.
• Negative Beta HCG test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization. Women of child bearing potential must be willing to use an effective contraceptive measure while on study.
• Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.

You may not qualify if:

• HIV seropositivity.
• Uncontrolled infections.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Popat UR, Mehta RS, Bassett R, Chen J, Valdez BC, Kawedia J, Ahmed S, Alousi AM, Anderlini P, Al-Atrash G, Bashir Q, Ciurea SO, Hosing CM, Im JS, Jones R, Kebriaei P, Khouri I, Marin D, Nieto Y, Olson A, Oran B, Parmar S, Rezvani K, Qazilbash MH, Shah N, Srour SA, Shpall EJ, Champlin RE, Andersson BS. Fludarabine with a higher versus lower dose of myeloablative timed-sequential busulfan in older patients and patients with comorbidities: an open-label, non-stratified, randomised phase 2 trial. Lancet Haematol. 2018 Nov;5(11):e532-e542. doi: 10.1016/S2352-3026(18)30156-X.

  PMID: 30389035 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Hodgkin Disease; Multiple Myeloma; Myelodysplastic Syndromes

Interventions

fludarabine phosphate; Busulfan; Tacrolimus; Methotrexate; Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Macrolides; Lactones; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Uday Popat, M.D. / Stem Cell Transplantation
• Organization: The University of Texas MD Anderson Cancer Center

upopat@mdanderson.org

713-792-8750

Study Officials

• Uday Popat, MD

  M.D. Anderson Cancer Center

  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: SPONSOR

Study Record Dates

• First Submitted: April 4, 2012
• First Posted: April 6, 2012
• Study Start: April 11, 2012
• Primary Completion: August 11, 2022
• Study Completion: August 11, 2022
• Last Updated: June 29, 2023
• Results First Posted: June 29, 2023

Record last verified: 2023-06

Locations

US (1)