Reduced Intensity Haploidentical BMT for High Risk Solid Tumors

• Register: ClinicalTrials.gov
• Last refreshed on: 8 April 2024
• Main ID: NCT01804634
• Date of registration: 01/03/2013
• Prospective Registration: Yes
• Primary sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Public title: Reduced Intensity Haploidentical BMT for High Risk Solid Tumors
• Scientific title: A Phase II Trial of Reduced Intensity Conditioning and Partially HLA-mismatched (HLA-haploidentical) Related Donor Bone Marrow Transplantation for High-risk Solid Tumors
• Date of first enrolment: March 27, 2013
• Target sample size: 60
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT01804634
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Heather Symons, MD, MHS

• Name: Heather Symons, MD, MHS
• Affiliation: Johns Hopkins University

Key inclusion & exclusion criteria

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.



Age minimum: 1 Year
Age maximum: 50 Years
Gender: All

Health Condition(s) or Problem(s) studied

Refractory and/or Relapsed Metastatic Solid Tumors

Intervention(s)

Drug: Cyclophosphamide

Drug: Fludarabine

Drug: Melphalan

Drug: Tacrolimus

Radiation: low dose total body irradiation

Primary Outcome(s)

Safety of Shortened duration of tacrolimus as assessed by number of participants with NRM and Grade III-IV acute GVHD at Day 120 [Time Frame: up to 120 Days]

Secondary Outcome(s)

chronic GVHD [Time Frame: 75days -1year]

Overall survival at 6 months [Time Frame: 6 months]

Event-free survival at 1 year [Time Frame: 1 year]

progression-free survival at 1 year [Time Frame: 1 year]

Event-free survival at 6 months [Time Frame: 6 months]

Non-Relapse Mortality [Time Frame: up to 2 years]

acute GVHD [Time Frame: 30-180]

progression-free survival at 6 months [Time Frame: 6 months]

Relapse [Time Frame: up to 2 years]

Overall survival at 1 year [Time Frame: 1 year]

Secondary ID(s)

J12106

NA_00076243

Source(s) of Monetary Support

Please refer to primary and secondary sponsors