URMC Related Haplo-identical Donor BMT

NCT02660281 | Completed Phase 1 DMC

• 1 other identifier: UBMT 15056
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be a single-center treatment protocol, designed to validate the process of related donor haploidentical-SCT at the Wilmot Cancer Institute Blood and Marrow Transplant Unit.

Conditions

Hematological Disease; Immune Deficiencies; Solid Tumors; Myelofibrosis; Multiple Myeloma; Lymphoma

Outcome Measures

Primary Outcomes (2)

• The number of days from the date of the stem cell infusion to engraftment of absolute neutrophils (ANC) and platelets (PLT) will be determined based on daily CBC and differential counts.

  The date of engraftment of ANC is the first of 3 consecutive days of ANC of 500 or higher. The date of engraftment of platelets is the first of 3 consecutive days of platelet counts of 20,000 or higher in the absence of platelet transfusions for at least 7 days prior.

  42 days following the infusion of stem cells for ANC. [If engraftment of ANC does not occur within 42 days, a subsequent transplant will be performed if a donor is available.

• Rate of non-engraftment and secondary graft failure

  The percentage of patients who fail to engraft ANC will be tabulated as well as the percentage of patients who have primary engraftment of ANC but whose graft then fails as evidenced by pancytopenia and failure of bone marrow function.

  At 100 days, 6 months, and yearly after transplant from the date of transplant until the date of documented graft failure or the subject's date of death up to 120 months.

Secondary Outcomes (7)

• Percentage of subjects who develop acute graft-versus-host disease.

  100 days following the infusion of stem cells

• Assess the Maximum Overall Grades 0- IV of acute GvHD and Maximum Severity (0-4) by involved organ system in patients who develop acute graft-versus-host disease.

  100 days following the infusion of stem cells

• Percentage of subjects who develop chronic graft-versus-host disease.

  Minimally at intervals of 100 days, 6 months and then yearly following the infusion of stem cells until the subject's date of death.or up to 120 months.

• Assess the Maximum Grade: Limited versus Extensive; Maximum Severity: Mild, Moderate or Severe) of chronic GvHD in patients who develop chronic graft-versus-

  Minimally at intervals of 100 days, 6 months and then yearly following the infusion of stem cells until the subject's date of death or up to 120 months.

• Disease-free survival

  Disease assessments are performed and reported at time points that include 100 days, 6 months, and yearly until documented progression of disease or the date of death or up to 120 months.

Study Arms (5)

Full Intensity TBI-based Conditioning

OTHER

Total Body Irradiation 1200 cGy of 150 cGy over 4 or 5 days, days -5 or -4 to -1 Fludarabine 30 mg/m2/day x 3 days, days -6, -5, -4 Stem Cell Infusion, day 0 Post- Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Mesna 50 mg/kg/day x 2 days, days +3 and +4

Radiation: Total Body Irradiation 1200 cGy; Drug: Fludarabine; Procedure: Stem Cell Infusion; Drug: Post-Stem Cell Infusion Cyclophosphamide; Drug: Post-Stem Cell Infusion Mesna

Full Intensity Chemo-Only Conditioning

OTHER

Fludarabine 25 mg/m2/day x 5 days, days -6, -5, -4, -3, -2 Busulfan 130 mg/m2/day x 4 days, days -6, -5, -4, -3 Pre-Stem Cell Infusion Cyclophosphamide 14.5 mg/kg/day x 2 days, days -3 and -2 Pre-Stem Cell Infusion Mesna 14.5 mg/kg/day x 2 days, days -3 and -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell Infusion Mesna 50 mg/kg/day x 2 days, days +3 and +4

Drug: Fludarabine; Drug: Pre-Stem Cell Infusion Cyclophosphamide; Drug: Pre-Stem Cell Infusion Mesna; Drug: Busulfan; Procedure: Stem Cell Infusion; Drug: Post-Stem Cell Infusion Cyclophosphamide; Drug: Post-Stem Cell Infusion Mesna

Reduced Intensity Conditioning

OTHER

Fludarabine 30 mg/m2/day x 5 days, days -6 to -2 Melphalan 140 mg/m2/day x 1 day, day -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell InfusionMesna 50 mg/kg/day x 2 days, days +3 and +4

Drug: Fludarabine; Drug: Melphalan; Procedure: Stem Cell Infusion; Drug: Post-Stem Cell Infusion Cyclophosphamide; Drug: Post-Stem Cell Infusion Mesna

Non-Myeloablative Conditioning

OTHER

Fludarabine 30 mg/m2/day x 5 days, days -6 to -2 Pre-Stem Cell Infusion Cyclophosphamide 14.5 mg/kg/day x 2 days, days -3 and -2 Pre-Stem Cell InfusionMesna 14.5 mg/kg/day x 2 days, days -3 and -2 Total Body Irradiation 200 cGy, day -1 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, day +3 and +4 Post-Stem Cell Infusion Mesna 50 mg/kg/day x 2 days, day +3 and +4

Radiation: Total Body Irradiation 1200 cGy; Drug: Fludarabine; Drug: Pre-Stem Cell Infusion Cyclophosphamide; Drug: Pre-Stem Cell Infusion Mesna; Procedure: Stem Cell Infusion; Drug: Post-Stem Cell Infusion Cyclophosphamide; Drug: Post-Stem Cell Infusion Mesna

Reduced Intensity Conditioning with Addition of Thiotepa

OTHER

Fludarabine 30 mg/m2/day x 5 days, days -6 to -2 Thiotepa 8 mg/kg, day -3 Melphalan 140 mg/m2/day x 1 day, day -2 Stem Cell Infusion, day 0 Post-Stem Cell Infusion Cyclophosphamide 50 mg/kg/day x 2 days, days +3 and +4 Post-Stem Cell InfusionMesna 50 mg/kg/day x 2 days, days +3 and +4

Drug: Fludarabine; Drug: Melphalan; Procedure: Stem Cell Infusion; Drug: Post-Stem Cell Infusion Cyclophosphamide; Drug: Post-Stem Cell Infusion Mesna; Drug: Thiotepa

Interventions

Total Body Irradiation 1200 cGy RADIATION

1200 cGy TBI in 8 fractions

Also known as: TBI

Full Intensity TBI-based Conditioning; Non-Myeloablative Conditioning

Fludarabine DRUG

Fludarabine

Full Intensity Chemo-Only Conditioning; Full Intensity TBI-based Conditioning; Non-Myeloablative Conditioning; Reduced Intensity Conditioning; Reduced Intensity Conditioning with Addition of Thiotepa

Pre-Stem Cell Infusion Cyclophosphamide DRUG

Cyclophosphamide given prior to the stem cell infusion

Full Intensity Chemo-Only Conditioning; Non-Myeloablative Conditioning

Pre-Stem Cell Infusion Mesna DRUG

Mesna given prior to the stem cell infusion

Full Intensity Chemo-Only Conditioning; Non-Myeloablative Conditioning

Busulfan DRUG

Busulfan

Full Intensity Chemo-Only Conditioning

Melphalan DRUG

Melphalan

Reduced Intensity Conditioning; Reduced Intensity Conditioning with Addition of Thiotepa

Stem Cell Infusion PROCEDURE

Stem cell infusion

Full Intensity Chemo-Only Conditioning; Full Intensity TBI-based Conditioning; Non-Myeloablative Conditioning; Reduced Intensity Conditioning; Reduced Intensity Conditioning with Addition of Thiotepa

Post-Stem Cell Infusion Cyclophosphamide DRUG

Cyclophosphamide given after the stem cell infusion

Full Intensity Chemo-Only Conditioning; Full Intensity TBI-based Conditioning; Non-Myeloablative Conditioning; Reduced Intensity Conditioning; Reduced Intensity Conditioning with Addition of Thiotepa

Post-Stem Cell Infusion Mesna DRUG

Mesna given after the Stem Cell Infusion

Full Intensity Chemo-Only Conditioning; Full Intensity TBI-based Conditioning; Non-Myeloablative Conditioning; Reduced Intensity Conditioning; Reduced Intensity Conditioning with Addition of Thiotepa

Thiotepa DRUG

Thiotepa

Reduced Intensity Conditioning with Addition of Thiotepa

Eligibility Criteria

• Age: 6 Months - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient Age:
• Pediatric (ages 6 months to 18 years)
• Adult (ages 18-75 years)
• Disease:
• Congenital and Other Non-malignant Disorders
• Immunodeficiency disorders (e.g. Severe Combined Immunodeficiency, Wiskott-Aldrich Syndrome)
• Congenital hematopoietic stem cell defects (e.g. Chediak-Higashi Syndrome, Congenital Osteopetrosis, Osteogenesis Imperfecta)
• Metabolic disorders (e.g. Hurler's Syndrome)
• Hemoglobinopathies (e.g. Sickle Cell Disease, Thalassemia)
• Severe aplastic anemia
• High-Risk Leukemias
• Acute Myelogenous Leukemia
• Refractory to standard induction therapy (more than 1 cycle required to achieve remission)
• Recurrent (in CR≥2)
• Treatment-related AML or MDS

You may not qualify if:

• Patient Age below 6 months or over 75 years
• Availability of a 10/10 HLA-matched related or unrelated donor within a reasonable time-frame dictated by the clinical urgency of the transplant
• Autologous HSCT \< 6 months prior to proposed haplo-SCT
• Pregnant or breast-feeding
• Current uncontrolled infection
• Evidence of HIV infection or positive HIV serology
• Anti-donor HLA antibodies with positive crossmatch and unsuccessful -

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

Wilmot Cancer Institute

Rochester, New York, 14642, United States

Location

MeSH Terms

Conditions

Hematologic Diseases; Primary Myelofibrosis; Multiple Myeloma; Lymphoma

Interventions

fludarabine; Busulfan; Melphalan; Thiotepa

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jeffrey Andolina, MD

  Wilmot Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Pediatric BMT

Study Record Dates

• First Submitted: November 24, 2015
• First Posted: January 21, 2016
• Study Start: October 1, 2015
• Primary Completion: October 28, 2019
• Study Completion: January 7, 2021
• Last Updated: November 3, 2021

Record last verified: 2021-11

Locations

US (1)