Safety Study of Bone Marrow Transplant Using Mismatched Tissue Followed by Chemotherapy

NCT00796562 | Completed Phase 2 Results DMC

• 3 other identifiers: J0820NA_00015795KL2RR025006
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to see if giving high dose chemotherapy and total body irradiation before and repeating high dose chemotherapy after a bone marrow transplant could reduce the incidence of graft rejection and disease for patients with blood cancers

Conditions

MDS; Leukemias; Lymphomas

Keywords

Leukemia; Lymphoma; Hematologic malignancies; ALL; AML; MDS; Transplantation; Mismatched; Haploidentical; Busulfan; Cyclophosphamide; Cellcept; Tacrolimus; TBI; CMMOL; CML; JMML

Outcome Measures

Primary Outcomes (1)

• Engraftment as Measured by Donor Chimerism

  Percentage of participants who achieved donor chimerism \>=95%.

  Day 60

Secondary Outcomes (5)

• Non-relapse Mortality

  Day 100, 1 year

• Acute GVHD

  Day 100

• Chronic GVHD

  6 months, 12 months

• Survival

  1 year, 2 years, 3 years

• Relapse

  1 year, 3 years

Study Arms (1)

Myeloablative haploidentical BMT

EXPERIMENTAL

* All participants except those with acute lymphoblastic leukemia and lymphoblastic lymphoma: Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days. * Participants with acute lymphocytic leukemia or lymphoblastic lymphoma: Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.

Drug: Busulfan; Drug: Cyclophosphamide; Radiation: Total body irradiation

Interventions

Busulfan DRUG

Participant will receive Busulfan injections, 4 times a day for 4 days with dilantin prophylaxis (in patients 10 years of age or older). Busulfan levels in the blood will be measured and dose adjusted, if needed.

Myeloablative haploidentical BMT

Cyclophosphamide DRUG

Patient will receive Cy by IV once a day for 2 days.

Also known as: Cy, Cytoxan, CTX

Myeloablative haploidentical BMT

Total body irradiation RADIATION

Patients will receive TBI once a day for 4 days.

Also known as: TBI

Myeloablative haploidentical BMT

Eligibility Criteria

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

You may qualify if:

• Acute lymphocytic leukemia in high risk CR1
• Acute myeloid leukemia in CR1
• Therapy-related AML
• RAEB with \>5% and \<20% bone marrow blasts
• Chronic myelogenous leukemia beyond 1st chronic phase; Patients cannot be in blast crisis
• CMMoL
• JMML
• Chemotherapy-resistant Hodgkins Lymphoma or intermediate or high grade Non-Hodgkins lymphoma (Less than a PR after standard or salvage chemotherapy)
• Mantle cell lymphoma: chemotherapy refractory (Less than a PR after standard or salvage chemotherapy) or patients beyond CR1 with chemosensitive disease
• Follicular Lymphoma, Grade 3
• Transformed indolent lymphomas

You may not qualify if:

• Poor cardiac function: left ventricular ejection fraction \<45% as determined by MUGA or ECHO. For pediatric patients LVEF \<45% or a shortening fraction below normal limits for age.
• Poor pulmonary function: FEV1 and FVC \<50% predicted for patients who have not received thoracic or mantle irradiation. For patients who have received thoracic or mantle irradiation, FEV1 and FVC \<70% predicted or DLCO \< 50 of predicted. For children unable to perform PFTs because of developmental stage pulse oximetry \< 85% on RA
• Poor liver function: bilirubin \>2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy)
• Poor renal function: Creatinine \>2.0mg/dl or creatinine clearance
• HIV-positive
• Positive leukocytotoxic crossmatch
• Women of childbearing potential who currently are pregnant or who are not practicing adequate contraception
• Uncontrolled viral, bacterial, or fungal infections Patients with symptoms consistent with RSV, influenza A, B, or parainfluenza at the time of enrollment will be assayed for the above viruses and if positive are not eligible for the trial until they are no longer symptomatic (patients may have continued assay positivity for a period of time post resolution of symptoms secondary to the nature of the assay.
• Indolent lymphomas (Follicular Grade 1 and 2, marginal zone, chronic lymphocytic leukemia, small lymphocytic lymphoma, MALT)

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Otsuka Pharmaceutical Co., Ltd.: collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (2)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Related Publications (2)

• Fine J.P. and Gray, R.J. (1999), A proportional hazards model for the subdistribution of a competing risk, Journal of the American Statistical Association, 94:496-509.

  BACKGROUND

• Symons HJ, Zahurak M, Cao Y, Chen A, Cooke K, Gamper C, Klein O, Llosa N, Zambidis ET, Ambinder R, Bolanos-Meade J, Borrello I, Brodsky R, DeZern A, Gojo I, Showel M, Swinnen L, Smith BD, Luznik L, Jones RJ, Fuchs EJ. Myeloablative haploidentical BMT with posttransplant cyclophosphamide for hematologic malignancies in children and adults. Blood Adv. 2020 Aug 25;4(16):3913-3925. doi: 10.1182/bloodadvances.2020001648.

  PMID: 32813874 DERIVED

MeSH Terms

Conditions

Leukemia; Lymphoma; Hematologic Neoplasms

Interventions

Busulfan; Cyclophosphamide; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques

Results Point of Contact

• Title: Heather Symons, MD
• Organization: Johns Hopkins University

hsymons2@jhmi.edu

4105029961

Study Officials

• Heather Symons, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: November 20, 2008
• First Posted: November 24, 2008
• Study Start: December 1, 2008
• Primary Completion: June 1, 2014
• Study Completion: November 1, 2016
• Last Updated: March 14, 2019
• Results First Posted: March 14, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)