Reduced Intensity Chemotherapy and Radiation Therapy Before Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

NCT02566304 | Completed Phase 2 Results DMC

• 4 other identifiers: 15D.3232015-054NCI-2015-01506JT 7773
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial studies the use of reduced intensity chemotherapy and radiation therapy before donor stem cell transplant in treating patients with hematologic malignancies. Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine phosphate, before a donor stem cell transplant may help 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). Reducing the intensity of the chemotherapy and radiation may also reduce the side effects of the donor stem cell transplant.

Conditions

Acute Myeloid Leukemia; Acute Myeloid Leukemia in Remission; Aplastic Anemia; Chronic Myelomonocytic Leukemia; Hodgkin Lymphoma; Indolent Non-Hodgkin Lymphoma; Malignant Neoplasm; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Plasma Cell Myeloma; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS will be estimated using Kaplan-Meier curves. The 1-year OS rate and corresponding 95% confidence interval will be estimated from the Kaplan-Meier curve for the OS.

  At 1 year post HSCT

Secondary Outcomes (5)

• Relapse Related Mortality (RRM)

  At 1 year post HSCT

• Non-Relapse Mortality (NRM)

  At 1 year post HSCT

• Incidence and Severity of GVHD

  Up to 1 year post HSCT

• Engraftment Rates

  Up to 1 year post HSCT

• Lymphoid Reconstitution

  Up to 1 year post HSCT

Study Arms (1)

RIC HSCT, GVHD prophylaxis

EXPERIMENTAL

RIC: Patients receive fludarabine phosphate IV on days -10 to -8 and cyclophosphamide IV on days -3 and -2. Patients also undergo TBI followed by a DLI on day -6. TRANSPLANT: Patients undergo CD34+ peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus PO beginning day -1 with a taper initiated on day 42 and mycophenolate mofetil IV BID on days -1 to 28 in the absence of GVHD.

Drug: Fludarabine; Radiation: Total-Body Irradiation; Biological: T Cell-Depleted Donor Lymphocyte Infusion; Drug: Cyclophosphamide; Procedure: Peripheral Blood Stem Cell Transplantation; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Other: Laboratory Biomarker Analysis

Interventions

Fludarabine DRUG

Given IV

Also known as: Fludarabine phosphate, Fludara

RIC HSCT, GVHD prophylaxis

Total-Body Irradiation RADIATION

Undergo TBI

RIC HSCT, GVHD prophylaxis

T Cell-Depleted Donor Lymphocyte Infusion BIOLOGICAL

Undergo DLI

RIC HSCT, GVHD prophylaxis

Cyclophosphamide DRUG

Given IV

Also known as: Endoxan, Cytoxan, Neosar, Procytox, Revimmune, Cycloblastin, Cytophosphane, CP

RIC HSCT, GVHD prophylaxis

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo PBSC transplant

RIC HSCT, GVHD prophylaxis

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo PBSC transplant

RIC HSCT, GVHD prophylaxis

Tacrolimus DRUG

Given PO

Also known as: FK-506, Fujimycin, Prograf, Advograf, Protopic

RIC HSCT, GVHD prophylaxis

Mycophenolate mofetil DRUG

Given IV

Also known as: Mycophenolic acid, MMF, CellCept, Myfortic

RIC HSCT, GVHD prophylaxis

Laboratory Biomarker Analysis OTHER

Correlative studies

RIC HSCT, GVHD prophylaxis

Eligibility Criteria

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

You may qualify if:

• Patients treated on this study will have:
• Acute myeloid leukemia in morphologic complete remission (CR) not requiring treatment for their disease for 4 weeks
• A history of acute myeloid leukemia (AML) with \< 10% residual blasts (use highest count on staging studies) after induction therapy and persisting with \< 10% blasts for at least 8 weeks without reinduction and at the time of HSCT
• Refractory anemia (RA) or refractory anemia with ring sideroblasts (RARS) or isolated 5q-
• Refractory anemia with excess blasts (RAEB)-1, refractory cytopenia with multilineage dysplasia (RCMD)+/-ringed sideroblasts (RS), or myelodysplastic syndrome (MDS) not otherwise specified (NOS) with stable disease for at least 3 months
• RAEB-2 must demonstrate chemo-responsiveness; chemo-responsiveness is defined as a persistent blast percentage decrease by at least 5 percentage points to therapy and there must be =\< 10% blasts (use highest count on staging studies) after treatment and at the time of transplant
• Hodgkin or Indolent non-Hodgkin's lymphoma
• Myeloma with \< 5% plasma cells in the marrow
• Myeloproliferative disorders (excludes chronic myelomonocytic leukemia \[CMML\])
• Aplastic anemia
• A hematological or oncological disease (not listed) in which allogeneic HSCT is thought to be beneficial, and the disease is chemoresponsive
• Patients without clear manifestation of their disease status in terms of stage and/or responsiveness should be discussed with the principal investigator (PI) and enrollment analysis should be documented in the study records
• Patients must have a related donor who is human leukocyte antigen (HLA) mismatched at 2, 3, or 4 antigens at the HLA-A; B; C; DR loci in the graft-versus-host disease (GVHD) direction; (patients with related donors who are HLA identical or are a 1-antigen mismatch may be treated on this therapeutic approach, but will have their outcomes will not be part of the statistical aims of the study); the HLA matched related category includes patients with a syngeneic donor
• Patients must have had front line therapy for their disease
• LVEF (left ventricular end diastolic function) of \>= 45%

You may not qualify if:

• Performance status \< 90% in patients 70 years old or greater, \< 80% in patients less than age 70 years
• HCT-CI/age score \> 5 points (patients with greater than 5 points will be allowed for trial with approval of the principal investigator and the co-principal investigator or his designee; this is an adjustment to account for healthy patients who meet the spirit of this protocol but have histories that result in higher than HCT-CI 5 points; an example is a patient with a solid tumor malignancy in their remote history \[adds 3 points to HCT-CI total\] where the treatment for the malignancy occurred years to decades before and there has been complete recovery of toxicities)
• A diagnosis of chronic myelomonocytic leukemia (CMML), unless in morphologic CR
• Human immunodeficiency virus (HIV) positive
• Active involvement of the central nervous system with malignancy
• Inability to obtain informed consent from patient or surrogate
• Pregnancy
• Patients with life expectancy of =\< 6 months for reasons other than their underlying hematologic/oncologic disorder
• Patients who have received alemtuzumab or antithymocyte globulin within 8 weeks of the transplant admission; the absence of these therapies in the medical record will serve as documentation that they were not given
• Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Jefferson University Hospitals

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Anemia, Aplastic; Leukemia, Myelomonocytic, Chronic; Hodgkin Disease; Neoplasms; Myelodysplastic Syndromes; Myeloproliferative Disorders; Multiple Myeloma; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts

Interventions

fludarabine; fludarabine phosphate; Whole-Body Irradiation; Cyclophosphamide; Peripheral Blood Stem Cell Transplantation; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Usama Gergis, MD
• Organization: Thomas Jefferson University

usama.gergis@jefferson.edu

215-955-8874

Study Officials

• Usama Gergis, MD

  Thomas Jefferson University

  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: SPONSOR

Study Record Dates

• First Submitted: September 30, 2015
• First Posted: October 2, 2015
• Study Start: November 13, 2015
• Primary Completion: February 13, 2024
• Study Completion: February 13, 2024
• Last Updated: April 24, 2025
• Results First Posted: March 20, 2025

Record last verified: 2025-04

Locations

US (1)