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Neoplasm MetastasisPhase 2NCT00001880

Stem Cell Transplantation for Metastatic Solid Tumors

A Phase 2 study testing methotrexate and Cyclosporin in people with Neoplasm Metastasis, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The goal of this research study is to identify other types of cancer (malignant neoplasms) that may be treatable with stem cell transplantation (allogenic peripheral blood stem cell transplantation. Read more about this study

Who is it for?
Ages 10 to 80 years
Conditions the study is for
Neoplasm Metastasis
What is being tested?
methotrexate and Cyclosporin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
12 Mar 1999to 13 Aug 2020
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 10 to 80 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • PATIENTS:
  • Patients with metastatic solid tumors ( breast, cholangiocarcinoma, small intestine/colon/rectal, adenocarcinoma, esophageal/gastric, hepatocellular, pancreatic, prostate, bony/soft tissue sarcomas, which are histologically confirmed, progressive and incurable.
  • Due to low accrual, effective 12/19/2006, patients with adrenal, basal cell, transitional cell carcinoma of the bladder or uroepithelium, ovarian, small cell lung cancer, non small cell lung cancer, and adenocarcinomas of unknown primary origin are no longer eligible for the trial.
  • Age greater than or equal to 10 to less than or equal to 80.
  • No known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy.
  • Metastatic disease, which is bi-dimensionally evaluable radiographically.
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  • No prior treatment for neoplasm within 30 days.
  • Ability to comprehend the investigational nature of the study and provide informed consent.
  • Availability of HLA identical or single HLA-locus mismatched family donor.
  • Willingness and availability to return to the NIH for scheduled follow-ups.
  • DONOR:
  • HLA identical or single HLA-locus mismatched family donor
  • Age greater than or equal to 10 up to 80 years old.
  • Ability to comprehend the investigational nature of the study and provide informed consent.

Who cannot join

  • PATIENT:
  • Pregnant or lactating.
  • Age less than 10 or greater than 80 years.
  • ECOG performance status of 3 or more.
  • Psychiatric disorder or mental deficiency severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible.
  • Major anticipated illness or organ failure incompatible with survival from PBSC transplant.
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  • DLCO: less than 40% predicted.
  • Left ventricular ejection fraction: less than 30%.
  • Serum creatinine greater than 2.5mg/dl or creatinine clearance less than 50 cc/min by 24 hr urine collection.
  • Serum bilirubin greater than 4 mg/dl
  • Transaminases greater than 5 times the upper limit of normal.
  • Oral intake less than 1,200 calories/day.
  • Recent weight loss of greater than or equal to 10% of actual body weight.
  • Life expectancy less than 3 months
  • Therapy for malignancy within 4 weeks of beginning protocol.
  • CNS metastatic disease associated with intracranial bleeding, uncontrolled seizure disorder or significant intracranial mass effect.
  • Other malignant diseases liable to relapse or progress within 5 years.
  • Uncontrolled infection.
  • DONOR:
  • Pregnant or lactating.
  • Donor unfit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension, history of congestive heart failure or unstable angina, thrombocytopenia).
  • Age less than 10 or greater than 80 years.
  • HIV positive. Donors who are positive for HBV, HCV or HTLV-I may be used at the discretion of the investigator following counseling and approval from the recipient.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Exploratory Study of Non-Myeloablative Allogeneic Stem Cell Transplantation and Donor Lymphocyte Infusions for Metastatic Neoplasms Refractory to Standard Therapy

The goal of this research study is to identify other types of cancer (malignant neoplasms) that may be treatable with stem cell transplantation (allogenic peripheral blood stem cell transplantation.

Patients with a variety of different types of cancerous tumors that have spread (metastasized) and whose conditions have not improved with stand therapy, will be eligible to participate. Those patients selected to participate in the study will undergo a procedure known as a "mini-transplant". The mini-transplant is a transplantation of stem-cells collected from a sibling (brother or sister) of the patient. Unlike traditional bone marrow transplants, the mini-transplant does not require intense chemotherapy or radiation therapy. Because of this, patients experience fewer and less severe side effects.

This study is open to patients diagnosed with a variety of metastatic solid tumors including esophageal, gastric (stomach), colon, rectal, liver tumors (hepatoma), cancer of the biliary system (cholangiocarcinoma), cancer of the pancreas, lung, breast, prostate, bone (sarcoma), adrenal basal cell, bladder, and adenocarcinomas of unk primary origin.

Read the detailed description

The main objective of this study is to identify metastatic neoplasms, which may be susceptible to the GVT effect. We will treat patients with progressive metastatic solid tumors refractory to standard therapy with a non-myeloablative allogeneic PBSC transplant from a family donor. A GVT effect from immunocompetent donor immune cells could extend life expectancy and possibly cure such patients.

Eligible patients will be treated with an allogeneic peripheral blood stem cell transplant from an HLA identical or single HLA antigen-mismatched family donor, using an intensive immunosuppressive regimen without myeloablation ("mini-transplant") in an attempt to decrease the transplant related toxicities while preserving the anti-malignancy and/or anti-host marrow effect of the graft. The low intensity non-myeloablative conditioning regimen should provide adequate immunosuppression to allow stem cell and lymphocyte engraftment. A T-cell replete, donor-derived, granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) will be used to establish hematopoietic and lymphoid reconstitution. We will infuse lymphocytes in patients with <100% donor T-cell chimerism or with evidence of tumor progression in an attempt to prevent graft rejection and enhance a graft-versus-malignancy effect, respectively.

This trial is open to several different types of metastatic, treatment-refractory, solid neoplasms, breast, cholangiocarcinoma, small intestine/colon/rectal adenocarcinoma, esophageal/gastric, hepatocellular, pancreatic, prostate, and bony/soft tissue sarcomas. The trial design permits up to 10 patients with a specific tumor type to be enrolled to screen for anti-tumor effects. A single complete response in a specific tumor type is an indication to exclude further patients with that diagnosis from the study. Subsequently, a new protocol which focuses on further defining a GVT effect in that disease category will be instituted.

Being tested
methotrexate, Cyclosporin
Keywords
Engraftment, Peripheral Blood Stem Cells, Non-Myeloablative Bone Marrow Transplantation, Metastatic Solid Tumors, Graft-Versus-Host Disease, Cancer, Tumor
Medical subject headings
Neoplasm Metastasis, Graft vs Host Disease, Neoplasms

What participants receive

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

  • methotrexateDrug

    Also called MTX (methotrexate)

    Cyclosporin beginning day -4 and intravenous Methotrexate on days +1, +3, and +6 will be given

  • CyclosporinDrug

    Also called CsA (Cyclosporin)

    Cyclosporin beginning day -4 and intravenous Methotrexate on days +1, +3, and +6 will be given

Study groups in NCT00001880
Study groupRoleWhat they receive
Stem Cell Transplantation in Patients With Progressive and Incurable Metastatic Solid TumorsExperimentalCyclosporin beginning day -4 then stem cells given on Day 0 followed by intravenous Methotrexate on days +1, +3, and +6.
Receives: Drug: methotrexate; Drug: Cyclosporin

What is being measured

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

  1. Number of Participants Based on Tumor Response Criteria With Anti-tumor Effect Induce by Graft-versus-tumor Effect.

    To identify an anti-tumor effect of allogenic PNSC transplantation by induction of a graft-versus-tumor (GVT) effect in patients with a diversity of metastatic solid tumors, which are refractory to standard therapy.

    Tumor response assessed as follows:

    Complete response (CR): disappearance of all signs and symptoms of metastatic disease for a period of at least one month.

    Partial response (PR): a 50% or greater decrease in the sum of the products of the longest perpendicular diameters of all measured lesions lasting for a period of at least one month. No new metastatic lesions may appear.

    Stable disease (SD): tumor measurements not meeting the criteria of CR, PR, or PD.

    Progressive disease (PD): increase of 25% or greater in the sum of the products of the longest perpendicular diameters of all measured lesions compared to the smallest previous measurements, or the development of any new metastatic disease.

    Measured: one year

Secondary outcomes (4)

  1. Number of Participants That Achieved Engraftment

    Number of participants that achieved engraftment based on blood Chimerism Cluster of differentiation 3 (CD3) analysis that is greater than or equal to 95%.

    Measured: Day 100

  2. Number of Participants Who Received Donor Lymphocyte Infusion to Achieve Tumor Regression or Prevent Graft Failure

    To evaluate the effects of donor lymphocyte infusion (DLI) and cyclosporine A (CSA) withdrawal on tumor regression in participants who show progressive disease off of CSA and in the absence of grade > II GVHD, or who are at risk for graft failure due to incomplete donor T-cell engraftment will receive one or more DLI.

    Tumor response assessed as follows:

    Complete response (CR): disappearance of signs \& symptoms of metastatic disease at least one month.

    Partial response (PR): a 50% or greater decrease in the sum of the products of the longest perpendicular diameters of all measured lesions lasting at least one month. No new metastatic lesions may appear.

    Stable disease (SD): tumor measurements not meeting the criteria of CR, PR, or PD.

    Progressive disease (PD): increase of 25% or greater in the sum of the products of the longest perpendicular diameters of all measured lesions compared to the smallest previous measurements, or development of new metastatic disease.

    Measured: 2 years

  3. Number of Participants Who Developed Acute GVHD Grade 2 and Higher

    Number of participants who developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV as defined by CIMBTR criteria for Organ Stages of Acute GVHD.

    Grades are defined as:

    Grade I: Skin = Maculopapular rash< 25% of body surface area (BSA); Liver = Total Bilirubin 2-3 mg/dL; Lower GI = stool output/day is 500-999 mL/day.

    Grade II: Skin = rash on 25-50 percent body surface area; Liver = Total Bilirubin 3.1-6.0 mg/dL; Lower GI = Diarrhea 1001-1500 mL/day.

    Grade III: Skin = Rash on >50% of body surface; Liver = Total Bilirubin 6.1 - 15.0 mg/dL; Lower GI = Diarrhea > 1500 mL/day.

    Grade IV: Skin = Generalized erythroderma plus bullous formation; Liver = Total Bilirubin >15 mg/dL; Lower GI = Severe abdominal pain with or without ileus.

    Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

    Measured: Day 100

  4. Number of Participants Who Developed Chronic GVHD

    Number of participants who developed Chronic Graft vs Host Disease (GVHD).

    Chronic GVHD is defined as symptoms that persist or appear after 100 days since the time of stem cell transplantation.

    Measured: Day 100 to year 2

Timeline

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

  1. First posted4 Nov 1999 (estimated)
  2. Study start12 Mar 1999
  3. Primary completion14 Aug 2008
  4. Study completion13 Aug 2020

Why it stopped: Study was closed early due to lack of accrual

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
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00001880
Sponsor's protocol ID
990064
Other IDs
99-H-0064
Status last verified
Aug 2020
First submitted
3 Jul 2006
Last updated
10 Nov 2021
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Eibl B, Schwaighofer H, Nachbaur D, Marth C, Gachter A, Knapp R, Bock G, Gassner C, Schiller L, Petersen F, Niederwieser D. Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer. Blood. 1996 Aug 15;88(4):1501-8.

    PubMed 8695872

  • Or R, Ackerstein A, Nagler A, Kapelushnik J, Naparstek E, Samuel S, Amar A, Bruatbar C, Slavin S. Allogeneic cell-mediated immunotherapy for breast cancer after autologous stem cell transplantation: a clinical pilot study. Cytokines Cell Mol Ther. 1998 Mar;4(1):1-6.

    PubMed 9557210

  • Ueno NT, Rondon G, Mirza NQ, Geisler DK, Anderlini P, Giralt SA, Andersson BS, Claxton DF, Gajewski JL, Khouri IF, Korbling M, Mehra RC, Przepiorka D, Rahman Z, Samuels BI, van Besien K, Hortobagyi GN, Champlin RE. Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer. J Clin Oncol. 1998 Mar;16(3):986-93. doi: 10.1200/JCO.1998.16.3.986.

    PubMed 9508181

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing methotrexate and Cyclosporin in people with Neoplasm Metastasis, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site 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 14 inclusion and 23 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: stopped early, as of the sponsor's last update on 10 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 10 Nov 2021). 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?

Number of Participants Based on Tumor Response Criteria With Anti-tumor Effect Induce by Graft-versus-tumor Effect. (time frame: one year). 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 NCT00001880, which also lists 3 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 10 Nov 2021.

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