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Organ-Sparing Marrow-Targeted Irradiation Before Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

Information source: Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: 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); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

Intervention: radiation therapy (Radiation); cyclophosphamide (Drug); anti-thymocyte globulin (Biological); tacrolimus (Drug); methotrexate (Drug); allogeneic bone marrow transplantation (Procedure); allogeneic hematopoietic stem cell transplantation (Procedure); peripheral blood stem cell transplantation (Procedure); laboratory biomarker analysis (Other)

Phase: N/A

Status: Recruiting

Sponsored by: Ohio State University Comprehensive Cancer Center

Official(s) and/or principal investigator(s):
Meng Welliver, MD, Principal Investigator, Affiliation: Ohio State University Comprehensive Cancer Center

Overall contact:
Ohio State University Comprehensive Cancer Center, Phone: 1-800-293-5066, Email: Jamesline@osumc.edu


This pilot clinical trial aims to assess feasibility and tolerability of using an LINAC based "organ-sparing marrow-targeted irradiation" to condition patients with high-risk hematological malignancies who are otherwise ineligible to undergo myeloablative Total body irradiation (TBI)-based conditioning prior to allogeneic stem cell transplant. The target patient populations are those with ALL, AML, MDS who are either elderly (>50 years of age) but healthy, or younger patients with worse medical comorbidities (HCT-Specific Comorbidity Index Score (HCT-CI) > 4). The goal is to have the patients benefit from potentially more efficacious myeloablative radiation based conditioning approach without the side effects associated with TBI.

Clinical Details

Official title: A Feasibility Study of Organ-Sparing Marrow-Targeted Irradiation (OSMI) to Condition Patients With High-Risk Hematologic Malignancies Prior to Allogeneic Hematopoietic Stem Cell Transplantation

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

TRM, defined as death occurring in a patient from causes other than disease relapse

Rate of grade II/III organ toxicity, defined by the Bearman Regimen-Related Toxicities Scale

Secondary outcome:


Donor chimerism

Incidence of aGVHD, graded according to Ohio State University Bone Marrow Transplant (OSU BMT) Program policy

Incidence of chronic GVHD, scored according to the OSU BMT Program policy

Cumulative incidence of grade II organ toxicity

Incidence of hematopoietic recovery

Incidence of graft failure

Rate of infectious complications

Incidence of relapse

Overall survival

Progression-free survival

Immune reconstitution

Detailed description: PRIMARY OBJECTIVES: I. To assess feasibility and tolerability of OSMI based hematopoietic stem cell transplant (HSCT) as defined by transplant-related mortality (TRM) at day 30 as well as rate of grade II/III organ toxicity (defined by Bearman Regimen-Related Toxicities Scale) attributable to conditioning occurring within 30 days. SECONDARY OBJECTIVES: I. Day 100 transplant-related mortality (TRM). II. Donor chimerism assessment at day 100 (to assess failure of engraftment rate). III. Incidence of acute graft-versus-host disease (aGVHD) by day 100. IV. Incidence of chronic GVHD at one year. V. Cumulative incidence of grade II organ toxicity through day 100. VI. Rate and kinetics of hematopoietic recovery. VII. Incidence of graft failure (primary and secondary). VIII. Rate of infectious complications. IX. Cumulative incidence of relapse, overall survival, and progression-free survival at 1 year. OUTLINE: CONDITIONING REGIMEN: Patients undergo organ-sparing marrow irradiation twice daily (BID) on

days - 6 to -4 and receive cyclophosphamide intravenously (IV) over 1-2 hours every 24 hours

on days - 3 to -2. Patients with an unrelated donor also receive anti-thymocyte globulin

every 24 hours on days - 4 to -2.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV or orally (PO) beginning on day - 1 and

continuing for at least 6 months and methotrexate IV on days 1, 3, 6, and 11. TRANSPLANT: Patients undergo allogeneic peripheral blood progenitor cell or bone marrow transplant on day 0. After completion of study treatment, patients are followed up weekly for 12 weeks, at day 100, and then at 6 and 12 months.


Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.


Inclusion Criteria:

- Patients with a diagnosis of acute myeloid leukemia (AML), acute lymphoblastic

leukemia (ALL), or myelodysplastic syndromes (MDS) with fewer than 10% myeloblasts or lymphoblasts in the bone marrow and no blasts in the peripheral blood on morphologic analysis performed within 30 days of start of the conditioning regimen; if remission bone marrow is available beyond 30 days a new bone marrow evaluation is required to assess remission status

- The diagnosis of AML, ALL, or MDS will be based on World Health Organization

(WHO) criteria

- Pre-transplant bone marrow sample must be evaluable for assessment of remission

status (i. e. aspirate smear containing particles and/or evaluable bone marrow core biopsy)

- Patients with leukemia infiltration in the central nervous system (CNS) are

eligible if cerebrospinal fluid (CSF) cytospin is negative for myeloblasts or lymphoblasts at time of enrollment

- If the patient has an intra-abdominal chloroma on presentation, and has a

partial response or complete response to treatment (size reduction of chloroma and marrow blast < 10%), the patient is eligible; however the chloroma must be included as part of the treatment target

- For patients receiving treatment of their AML, MDS or ALL prior to transplantation:

- Interval between the start of a cycle of conventional cytotoxic chemotherapy and

the start of conditioning regimen must be at least 30 days

- Interval between completing treatment with a hypomethylating agent or other

non-cytotoxic chemotherapy and the start of conditioning regimen must be at least 10 days

- Hematopoietic Cell Transplantation-Specific Comorbidity Index score (HCT-CI) =< 4 for

patients in Cohort 1 and > 4 for Cohort 2

- Patient must be able to lie still in full body cast for 45 minutes

- Must have a suitable donor defined as a sibling matched at 5/6 or 6/6 antigens (human

leukocyte antigen [HLA]-A, B, and DRB1) or an unrelated volunteer matched at 7/8 or 8/8 HLA alleles (HLA-A, B, C, and DRB1)

- Signed informed consent

- DONOR: "High resolution" typing at HLA-A, B, C and DRB1 alleles

- Single antigen mismatch for siblings and single allele mismatch for volunteer

unrelated donors is acceptable

- Donors must be >= 17 years of age

Exclusion Criteria:

- Circulating peripheral blood myeloblasts or lymphoblasts on morphologic analysis from

time of last treatment to time of enrollment

- Prior allograft or prior autograft

- Active CNS disease as identified by positive CSF cytospin at time of enrollment

- Karnofsky performance score < 70

- Symptomatic uncontrolled coronary artery disease or ejection fraction < 40%

- Total bilirubin >= 2 x the upper limit of normal

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >= 3 x the upper

limit of normal

- Diffusion capacity of the lung for carbon monoxide (DLCO) < 40%

- Forced expiratory volume in one second (FEV1) < 50% (corrected for hemoglobin)

- Receiving supplementary continuous oxygen

- Creatinine clearance < 50 mL/min/1. 73m^2

- Patients with active uncontrolled bacterial, viral or fungal infections (undergoing

appropriate treatment and with progression of clinical symptoms)

- Patients seropositive for the human immunodeficiency virus (HIV)

- Females who are pregnant or breastfeeding

- Fertile men and women unwilling to use contraceptive techniques during and for 12

months following treatment

- Patients who had prior radiation to more than 20% bone marrow containing areas or to

any areas exceeding 2000 cGy


- Donors will be excluded if they are an identical twin of the recipient

- Females who are pregnant (positive serum beta human chorionic gonadotropin beta

[β HCG]) or uninterruptible breastfeeding

- HIV seropositive

- Donors receiving experimental therapy or investigational agents unless approved

by the protocol chair

Locations and Contacts

Ohio State University Comprehensive Cancer Center, Phone: 1-800-293-5066, Email: Jamesline@osumc.edu

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center, Columbus, Ohio 43210, United States; Recruiting
Meng X. Welliver, Phone: 614-293-0216, Email: Meng.Welliver@osumc.edu
Meng X. Welliver, MD, Principal Investigator
Additional Information

The Jamesline

Starting date: June 2015
Last updated: July 27, 2015

Page last updated: August 20, 2015

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