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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Collaborators:
Otsuka Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00796562
First received: November 20, 2008
Last updated: March 23, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
MDS
Leukemias
Lymphomas
Drug: Drug: busulfan, Cyclophosphamide, Total Body Irradiation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Screening
Official Title: A Phase II Trial of Myeloablative Conditioning and Transplantation of Partially HLA-mismatched Bone Marrow for Patients With Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • To estimate the incidence of donor cell engraftment following myeloablative, HLA-mismatched BMT for patients with high risk hematologic malignancies. [ Time Frame: Day 14-60 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To estimate overall survival, relapse, non-relapse mortality, and event-free survival in patients receiving myeloablative conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow from first-degree relatives [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 96
Study Start Date: November 2008
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
All patients except those with acute lymphoblastic leukemias and lymphoblastic lymphomas
Drug: Drug: busulfan, Cyclophosphamide, Total Body Irradiation

Arm A:

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

Arm B:

Patients will start on Cy IV once a day for 2 days followed by TBI once a day for 4 days.

Transplant:

Bone Marrow Transplant will follow busulfan/Cy or Cy/TBI preparative regimen.

Other Names:
  • Busulfan
  • Cyclophosphamide
  • Cy
  • Cytoxan
  • Total Body Irradiation
Active Comparator: Arm B
Patients with acute lymphocytic leukemia or lymphoblastic lymphoma
Drug: Drug: busulfan, Cyclophosphamide, Total Body Irradiation

Arm A:

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

Arm B:

Patients will start on Cy IV once a day for 2 days followed by TBI once a day for 4 days.

Transplant:

Bone Marrow Transplant will follow busulfan/Cy or Cy/TBI preparative regimen.

Other Names:
  • Busulfan
  • Cyclophosphamide
  • Cy
  • Cytoxan
  • Total Body Irradiation

Detailed Description:

Allogeneic blood or marrow transplantation (alloBMT), following either marrow-ablative or nonmyeloablative conditioning, is a potentially curative treatment for a variety of hematologic malignancies and non-malignant hematologic disorders. Of all the potential sources of allografts, transplantation of stem cells from a human leukocyte antigen (HLA)-matched sibling has generally produced the best overall outcomes, i.e. overall and progression-free survival. Unfortunately, only about a third of candidates for alloBMT have HLA-matched siblings.

For patients who lack HLA-matched siblings, there are three alternative sources of stem cells for alloBMT: 1) volunteer unrelated donors; 2) umbilical cord blood; and 3) partially HLA-mismatched, or haploidentical, related donors. Since any patient shares exactly one HLA haplotype with each biological parent or child and half of siblings, an eligible haploidentical donor can be identified rapidly in nearly all cases. However, haploidentical BMT has been associated with significant risks of graft rejection and severe GVHD, which are manifestations of excessive alloreactivity by host and donor T cells, respectively.

The risk of severe GVHD may be reduced in intensively conditioned recipients of grafts that have been rigorously depleted of mature T cells or selectively depleted of alloreactive T cells, but the risks of serious infection and death from prolonged immune compromise in these patients remains high. Cyclophosphamide(Cy) is a highly immunosuppressive antineoplastic agent that has an established role in conditioning for alloBMT.

Typically, the drug is administered prior to transplantation to prevent graft rejection by suppressing the host immune system. However, pre-transplantation conditioning with Cy increases the risk of GVHD following allogeneic T cell infusion in mouse models. In contrast, administration of a properly timed, high dose of Cy after BMT inhibits both graft rejection and GVHD.

  Eligibility

Ages Eligible for Study:   6 Months to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00796562

Contacts
Contact: Heather Symons, M.D. 410-502-9961 hsymons2@jhmi.edu

Locations
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231
Contact: Heather Symons, M.D.       hsymons2@jhmi.edu   
Principal Investigator: Heather Symons, M.D.         
Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Heather Symons, MD    410-502-9961    hsymons2@jhm.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Otsuka Pharmaceutical Co., Ltd.
Investigators
Principal Investigator: Heather Symons, M.D. Johns Hopkins University
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00796562     History of Changes
Other Study ID Numbers: J0820, NA_00015795, KL2RR025006
Study First Received: November 20, 2008
Last Updated: March 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
Leukemia
Lymphoma
Hematologic malignancies
ALL
AML
MDS
Transplantation
Mismatched
Haploidentical
Busulfan
Cyclophosphamide
Cellcept
Tacrolimus
TBI
CMMOL
CML
JMML

Additional relevant MeSH terms:
Leukemia
Lymphoma
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Hematologic Diseases
Busulfan
Cyclophosphamide
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 26, 2014