Reduced Intensity Haploidentical BMT for High Risk Solid Tumors

NCT01804634 | Recruiting Phase 2 DMC

• 3 other identifiers: J12106NA_000762435P01CA225618-06
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to see if giving reduced intensity chemotherapy, haploidentical bone marrow, post-transplant cyclophosphamide and shortened duration tacrolimus is safe and feasible for patients with very high-risk solid tumors.

Conditions

Refractory and/or Relapsed Metastatic Solid Tumors

Keywords

Solid Tumors; Neuroblastoma; Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Hepatoblastoma; Desmoplastic Round Cell Tumor

Outcome Measures

Primary Outcomes (1)

• Safety of Shortened duration of tacrolimus as assessed by number of participants with NRM and Grade III-IV acute GVHD at Day 120

  Safety of shortened duration immunosuppression assessed by the number of participants with non-relapse mortality (NRM) and grade III-IV acute graft versus host disease (Przepiorka criteria stages the degree of organ involvement in the skin, liver and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least sever and Stage 4+ being most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, liver 4+))

  up to 120 Days

Secondary Outcomes (10)

• Overall survival at 6 months

  6 months

• Overall survival at 1 year

  1 year

• Relapse

  up to 2 years

• Non-Relapse Mortality

  up to 2 years

• Event-free survival at 6 months

  6 months

Other Outcomes (4)

• Document toxicities

  30-180 days

• To compare the tumor microenvironment, circulating tumor cells, and expression of MHC antigens as well as tumor specific antigens pre- and post BMT

  30days-180 days

• To document the incidence of significant viral, bacterial and fungal infections

  0-180 days

Study Arms (1)

Reduced intensity conditioning

EXPERIMENTAL

Fludarabine IV infusion over 30 minutes on D-7 to D-3. The dose will be 30 mg/m2/dose (adjusted for renal function). Melphalan: IV infusion over 30-60 minutes, depending on volume, on D-2. The dose will be 100mg/m2.Total body irradiation: 200 cGy AP/PA with 4MV or 6MV photons at 8 12 cGy/min at the point of prescription (average separation of measurements at mediastinum, abdomen, and hips) will be administered in a single fraction on day -1. Bone Marrow will be harvested and infused on day 0. Post-transplantation Cyclophosphamide 50mg/kg will be given on D+3 post-transplant (within 60-72 hr of marrow infusion) and on D+4 post-transplant. Tacrolimus begins on Day 5, at least 24 hours after completion of posttransplantation Cy at 0.015mg/kg IBW/dose IV over 3 hours every 12 hours. Mycophenolic acid mofetil (MMF) F will be given at a dose of 15 mg/kg PO TID (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams (1 g PO TID).

Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: low dose total body irradiation; Drug: Melphalan; Drug: Tacrolimus

Interventions

Cyclophosphamide DRUG

preparative regimen

Also known as: cytoxan

Reduced intensity conditioning

Fludarabine DRUG

Also known as: Flu

Reduced intensity conditioning

Melphalan DRUG

Also known as: Mel

Reduced intensity conditioning

low dose total body irradiation RADIATION

Also known as: TBI

Reduced intensity conditioning

Tacrolimus DRUG

Also known as: tacro

Reduced intensity conditioning

Eligibility Criteria

• Age: 1 Year - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

Presence of a suitable related HLA-haploidentical bone marrow donor.a. The donor and recipient must be identical at at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. A minimum match of 5/10 is therefore required, and will be considered sufficient evidence that the donor and recipient share one HLA haplotype. 1 year-50 years Patients must have a confirmed histopathologic diagnosis and be classified as high risk defined by having an expected survival of \< 10%. Examples include: * Neuroblastoma or ganglioneuroblastoma * Failure to achieve at least a PR after induction therapy with COG ANBL0532 or standard chemotherapy * Refractory to induction chemotherapy with COG ANBL0532 or standard chemotherapy * Patients with high risk disease as defined in Appendix 1 whose autologous peripheral blood stem cell product is contaminated with neuroblastoma or who do not have an autologous product available * Patients with high risk disease as defined in Appendix 1 who do not meet eligibility requirements/organ function requirements for myeloablative conditioning. Patients with \>5 identified lesions on the end of induction (COG ANBL0532 or standard chemotherapy) MIBG scan * Stage 4 rhabdomyosarcoma * Metastatic Ewing Sarcoma * Osteosarcoma with metastatic disease beyond the lungs and/or with lung metastases not amenable to resection * Desmoplastic small round cell tumor * Any other solid tumor and soft tissue sarcoma with an estimated \<10% chance of survival will be considered on a case by case basis at the departmental tumor board and/or sarcoma meeting Previous therapy: * It is expected that patients will have received upfront standard of care therapy for their respected disease * Patients who relapse after either single or tandem autologous BMT are eligible (\> 6 months must have elapsed from start of last BMT). * Patients must be recovered from the acute toxicities of any prior chemo/radio/immunotherapy or BMT Patients do not need to have measurable disease at time of enrollment. Patients with measurable disease must have stable disease by RECIST criteria on two scans at least 6 weeks apart. Patients with adequate organ function as measured by * Cardiac: Left ventricular ejection fraction at rest must be ≥ 35%, or shortening fraction \> 25%. * Hepatic: Bilirubin ≤ 3.0 mg/dL; and ALT, AST, and Alkaline Phosphatase \< 5 x ULN. * Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or GFR) \> 40 mL/min/1.73m2. * Pulmonary: FEV1, FVC, DLCO (diffusion capacity) \> 50% predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation \> 92% on room air. Good performance status (Karnofsky/Lansky 60-100) Patients (Parents/guardians for those \<18) and donors must be able to sign consent forms. Patients must be willing to participate in all stages of treatment Criteria for recipient ineligibility Patients will not be excluded on the basis of sex, racial or ethnic background. HIV-positive Donor (donor anti-recipient) ABO incompatibility if an ABO compatible donor is available. Positive leukocytotoxic crossmatch Women of childbearing potential who currently are pregnant (HCG+) or who are not practicing adequate contraception Uncontrolled viral, bacterial, or fungal infections. Criteria for donor eligibility Age \>0.5 years Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FACT). Lack of recipient anti-donor HLA antibody Note: In some instances, low level, non-cytotoxic HLA specific antibodies may be permissible if they are found to be at a level well below that detectable by flow cytometry. This will be decided on a case-by-case basis by the PI and one of the immunogenetics directors. In the event that two or more eligible donors are identified, the following order of priority will be used to determine the preferred donor: 1. Medically and psychologically fit and willing to donate 2. Killer Immunoglobulin Receptor (KIR) Haplotype B Donor 3. Red blood-cell compatibility (in order of preference) 1. RBC cross-match compatible 2. Minor ABO incompatibility 3. Major ABO incompatibility 4. For CMV seronegative recipients, a CMV seronegative donor. For CMV seropositive recipients, a CMV seropositive donor is preferred. 5. When possible, HLA-mismatched donors will be prioritized over HLA-matched to maximize an allogeneic benefit. If more than one preferred donor is identified from the above list and there is no medical reason to prefer one of them, then the following guidelines are recommended: 1. If the patient is male, choose a male donor 2. Choose the youngest preferred donor 3. If the patient and family express a strong preference for a particular donor, use that one.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (3)

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

RECRUITING

Albert Einstein College of Medicine, Children's Hospital at Montefiore

The Bronx, New York, 10467, United States

RECRUITING

New York Medical Center/ Maria Fareri Children's Hospital

Valhalla, New York, 10595, United States

RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Osteosarcoma; Sarcoma, Ewing; Rhabdomyosarcoma; Hepatoblastoma

Interventions

Cyclophosphamide; fludarabine; Influenza Vaccines; Whole-Body Irradiation; Melphalan; Honey; Tacrolimus

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Complex and Mixed

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Radiotherapy; Therapeutics; Investigative Techniques; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Macrolides; Lactones

Study Officials

• Heather Symons, MD, MHS

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heather Symons, MD, MHS

CONTACT

410-502-4997; hsymons2@jhmi.edu

Jasmine Brooks, BA

CONTACT

667-306-8335; jbrook54@jhmi.edu

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: March 1, 2013
• First Posted: March 5, 2013
• Study Start: March 27, 2013
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2030
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

US (3)