AzTrials
AzTrials

MDSPhase 2NCT00796562

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

A Phase 2 study testing Busulfan, Cyclophosphamide and Total body irradiation in people with MDS and Leukemias, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 6 months to 65 years
Conditions the study is for
MDS, Leukemias, Lymphomas
What is being tested?
Busulfan, Cyclophosphamide and Total body irradiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
107 participants
Where
2 sitesUnited States
Study dates
Dec 2008to Nov 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • 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)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21231

  • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231

Other trials in United States

About this study

Official title: A Phase II Trial of Myeloablative Conditioning and Transplantation of Partially HLA-mismatched Bone Marrow for Patients With Hematologic Malignancies

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

Read the 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.

Conditions
MDS, Leukemias, Lymphomas
Keywords
Leukemia, Lymphoma, Hematologic malignancies, ALL, AML, MDS, Transplantation, Mismatched, Haploidentical, Busulfan, Cyclophosphamide, Cellcept, Tacrolimus, TBI, CMMOL, CML, JMML
Medical subject headings
Leukemia, Lymphoma, Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BusulfanDrug

    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.

  • CyclophosphamideDrug

    Also called Cy, Cytoxan, CTX

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

  • Total body irradiationRadiation

    Also called TBI

    Patients will receive TBI once a day for 4 days.

Study groups in NCT00796562
Study groupRoleWhat they receive
Myeloablative haploidentical BMTExperimental* 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.
Receives: Drug: Busulfan; Drug: Cyclophosphamide; Radiation: Total body irradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Engraftment as Measured by Donor Chimerism

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

    Measured: Day 60

Secondary outcomes (5)

  1. Non-relapse Mortality

    Number of participants deceased for reasons other than disease relapse or progression.

    Measured: Day 100, 1 year

  2. Acute GVHD

    Percentage of participants who experience grade II-IV or III-IV acute graft-versus-host-disease (GVHD) by Przepiorka criteria. The stages are defined as follows:

    • Stage II: Rash on >50% of skin, bilirubin 2-3 mg/dL, or diarrhea 500-1000 mL/day
    • Stage III: Bilirubin 3-15 mg/dL or diarrhea >1000 mL/day
    • Stage IV: Generalized erythroderma with bullae or bilirubin >15 mg/dL This outcome was estimated using proportional subdistribution hazard regression model for competing risks (Fine and Gray 1999)

    Measured: Day 100

  3. Chronic GVHD

    Percentage of participants who experience chronic GVHD. Chronic GVHD is graded using NIH consensus criteria and Seattle criteria. This outcome was estimated using proportional subdistribution hazard regression model for competing risks (Fine and Gray 1999)

    Measured: 6 months, 12 months

  4. Survival

    Percentage of participants alive (overall survival) and alive without disease relapse, progression, or diagnosis of myeloid malignancy (event-free survival). Estimated using Kaplan-Meier method.

    Measured: 1 year, 2 years, 3 years

  5. Relapse

    Percentage of participants who experienced disease progression or relapse. This outcome was estimated using proportional subdistribution hazard regression model for competing risks (Fine and Gray 1999)

    Measured: 1 year, 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Nov 2008 (estimated)
  2. Study startDec 2008
  3. Primary completionJun 2014
  4. Study completionNov 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
107 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00796562
Sponsor's protocol ID
J0820
Other IDs
NA_00015795, KL2RR025006
Status last verified
Mar 2019
First submitted
20 Nov 2008
Last updated
14 Mar 2019
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

  • 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.

    PubMed 32813874

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Busulfan, Cyclophosphamide and Total body irradiation in people with MDS and Leukemias, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Engraftment as Measured by Donor Chimerism (time frame: Day 60). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00796562, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in