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

NCT ID: NCT02122081

Last Updated: 2023-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-27
• Study Completion Date: 2022-09-06

Brief Summary

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.

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (OSMI, allogeneic transplant)

CONDITIONING REGIMEN: Patients undergo organ-sparing marrow irradiation BID on days -6 to -4 and receive cyclophosphamide 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 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.

Group Type: EXPERIMENTAL

radiation therapy

Intervention Type: RADIATION

Undergo organ-sparing marrow irradiation BID on days -6 to -4

cyclophosphamide

Intervention Type: DRUG

Given IV over 1-2 hours every 24 hours on days -3 to -2.

anti-thymocyte globulin

Intervention Type: BIOLOGICAL

tacrolimus

Intervention Type: DRUG

Given IV or PO

methotrexate

Intervention Type: DRUG

Given IV

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

Undergo allogeneic peripheral blood progenitor cell or bone marrow transplant on day 0

allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Undergo allogeneic peripheral blood progenitor cell or bone marrow transplant

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Undergo allogeneic peripheral blood progenitor cell or bone marrow transplant

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

radiation therapy

Undergo organ-sparing marrow irradiation BID on days -6 to -4

Intervention Type: RADIATION

cyclophosphamide

Given IV over 1-2 hours every 24 hours on days -3 to -2.

Intervention Type: DRUG

anti-thymocyte globulin

Intervention Type: BIOLOGICAL

tacrolimus

Given IV or PO

Intervention Type: DRUG

methotrexate

Given IV

Intervention Type: DRUG

allogeneic bone marrow transplantation

Undergo allogeneic peripheral blood progenitor cell or bone marrow transplant on day 0

Intervention Type: PROCEDURE

allogeneic hematopoietic stem cell transplantation

Undergo allogeneic peripheral blood progenitor cell or bone marrow transplant

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Undergo allogeneic peripheral blood progenitor cell or bone marrow transplant

Intervention Type: PROCEDURE

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

irradiation; radiotherapy; therapy, radiation; CPM; CTX; Cytoxan; Endoxan; Endoxana; ATG; ATGAM; lymphocyte immune globulin; Thymoglobulin; FK 506; Prograf; amethopterin; Folex; methylaminopterin; Mexate; MTX; bone marrow therapy, allogeneic; bone marrow therapy, allogenic; transplantation, allogeneic bone marrow; transplantation, allogenic bone marrow; PBPC transplantation; PBSC transplantation; peripheral blood progenitor cell transplantation; transplantation, peripheral blood stem cell

Eligibility Criteria

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
• DONOR:

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sumithira Vasu

OTHER

Sponsor Role: lead

Responsible Party

Sumithira Vasu

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sumithira Vasu, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Locations

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, United States

Countries

United States

Related Links

http://cancer.osu.edu

The Jamesline

Other Identifiers

NCI-2014-00763

Identifier Type: REGISTRY

Identifier Source: secondary_id

OSU-13219

Identifier Type: -

Identifier Source: org_study_id