Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

NCT00860574 | Completed Phase 2 Results DMC

• 3 other identifiers: 2272.00NCI-2010-00315P01HL036444
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial is studying how well giving treosulfan together with fludarabine phosphate and total-body irradiation followed by donor stem cell transplant works in treating patients with high-risk acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia. Giving chemotherapy, such as treosulfan and fludarabine phosphate, and total-body irradiation before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and methotrexate before and after transplant may stop this from happening

Conditions

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• Relapse Incidence

  At 6 months

• Non Relapse Mortality (NRM) Incidence

  Cumulative incidence of NRM at 6 months. NRM includes all deaths without relapse or disease progression.

  At 6 months

Secondary Outcomes (6)

• Non Relapse Mortality Incidence

  1 year after HCT

• Overall Survival (OS)

  at 2 years

• Relapse-free Survival

  at 2 years

• Incidence of Grades II-IV Acute GVHD

  at 6 months

• Incidence of Chronic GVHD

  at 6 months

Study Arms (1)

Treatment (allogeneic transplantation)

EXPERIMENTAL

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or PO BID on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Drug: treosulfan; Drug: fludarabine phosphate; Radiation: total-body irradiation; Procedure: peripheral blood stem cell transplantation; Drug: tacrolimus; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Drug: methotrexate

Interventions

treosulfan DRUG

Given IV

Also known as: dihydroxybusulfan, Ovastat, tresulfon

Treatment (allogeneic transplantation)

fludarabine phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Treatment (allogeneic transplantation)

total-body irradiation RADIATION

Low dose starting at 2Gy

Also known as: TBI

Treatment (allogeneic transplantation)

peripheral blood stem cell transplantation PROCEDURE

Given IV per institutional standard practice

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Treatment (allogeneic transplantation)

tacrolimus DRUG

Given IV or PO

Also known as: FK 506, Prograf

Treatment (allogeneic transplantation)

allogeneic bone marrow transplantation PROCEDURE

Given IV per institutional standard practice

Also known as: bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow

Treatment (allogeneic transplantation)

allogeneic hematopoietic stem cell transplantation PROCEDURE

Given IV per institutional standard practice

Treatment (allogeneic transplantation)

methotrexate DRUG

Given IV

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX

Treatment (allogeneic transplantation)

Eligibility Criteria

• Age: Up to 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Acute myeloid leukemia (AML):
• All AML patients beyond 1st remission;
• Intermediate or high risk AML patients (based on South West Oncology Group \[SWOG\] cytogenetic criteria) in 1st complete remission
• Myelodysplastic syndrome (MDS)
• Other myeloid malignancies as chronic myelogenous leukemia (CML), CML accelerated phase, CML blast crisis, chronic myelomonocytic leukemia (CMML) (to be approved by patient care conference \[PCC\])
• With Karnofsky Index or Lansky Play-Performance Scale \> 70% on pre-transplant evaluation
• Able to give informed consent (if \> 18 years), or with a legal guardian capable of giving informed consent (if \< 18 years)
• Previous autologous or allogeneic HCT is allowed
• Donors must be:
• Human leukocyte antigen (HLA)-identical related donors or
• Unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 defined by high resolution deoxyribonucleic acid (DNA) typing or mismatched for one HLA allele, except for HLA-C where no mismatch is allowed
• Able to undergo peripheral blood stem cell collection or bone marrow harvest
• In good general health, with a Karnofsky or Lansky Play Performance score \> 90%
• Able to give informed consent (if \> 18 years), or with a legal guardian capable of giving informed consent (if \< 18 years)
• Acute lymphoblastic leukemia (ALL): all ALL patients not eligible for other protocols

You may not qualify if:

• Receiving umbilical cord blood
• With impaired cardiac function as evidenced by ejection fraction \< 35% or cardiac insufficiency requiring treatment or symptomatic coronary artery disease
• With impaired pulmonary function as evidenced by partial pressure of oxygen (pO2) \< 70 mm Hg and diffusing capacity of the lung for carbon monoxide (DLCO) \< 70% of predicted or pO2 \< 80 mm Hg and DLCO \< 60% of predicted; or receiving supplementary continuous oxygen
• With impaired renal function as evidenced by creatinine-clearance \< 50% for age, weight, height or serum creatinine \> 2x upper normal limit or dialysis-dependent
• With hepatic dysfunction as evidenced by total bilirubin or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.0 x upper normal limit or evidence of synthetic dysfunction or severe cirrhosis
• With active infectious disease requiring deferral of conditioning, as recommended by an Infectious Disease specialist
• With human immunodeficiency virus (HIV)-positivity or active infectious hepatitis because of possible risk of lethal infection when treated with immunosuppressive therapy
• With central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiation prior to initiating conditioning (day -6)
• With life expectancy severely limited by diseases other than malignancy
• Women who are pregnant or lactating because of possible risk to the fetus or infant
• With known hypersensitivity to treosulfan and/or fludarabine
• Receiving another experimental drug within 4 weeks before initiation of conditioning (day -6)
• Unable to give informed consent (if \> 18 years) or with a legal guardian (if \< 18 years) unable to give informed consent
• Ineligible donors will be those:
• Deemed unable to undergo marrow harvesting or PBSC mobilization and leukapheresis

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (3)

University of Colorado

Denver, Colorado, 80217-3364, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Congenital Abnormalities; Blast Crisis; Leukemia, Myelomonocytic, Chronic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute

Interventions

treosulfan; fludarabine phosphate; Whole-Body Irradiation; Peripheral Blood Stem Cell Transplantation; Tacrolimus; Transplantation; Methotrexate; merphos

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Surgical Procedures, Operative; Macrolides; Lactones; Organic Chemicals; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Joachim Deeg
• Organization: Fred Hutch/University of Washington Cancer Consortium

jdeeg@fredhutch.org

206.667.5985

Study Officials

• Boglarka Gyurkocza

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: Investigator

Study Record Dates

• First Submitted: March 11, 2009
• First Posted: March 12, 2009
• Study Start: February 1, 2009
• Primary Completion: February 1, 2013
• Last Updated: June 22, 2021
• Results First Posted: February 26, 2021

Record last verified: 2021-02

Locations

US (3)