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LymphomaPhase 1NCT00244946

Combination Chemotherapy Followed By Autologous Stem Cell Transplant, and White Blood Cell Infusions in Treating Patients With Non-Hodgkin's Lymphoma

A Phase 1 study testing therapeutic autologous lymphocytes, carmustine and cytarabine in people with Lymphoma, run by Barbara Ann Karmanos Cancer Institute at 1 site in United States.

Completed

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

Official record
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Trial summary

RATIONALE: Drugs used in chemotherapy, such as carmustine, etoposide, cytarabine, and melphalan work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Read more about this study

Who is it for?
Ages 15 to 70 years
Conditions the study is for
Lymphoma
What is being tested?
therapeutic autologous lymphocytes, carmustine and cytarabine
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
Mar 2004to Mar 2013
Phase
Phase 1
Are there results?
None posted in the registry

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 15 to 70 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed CD20+ non-Hodgkin's lymphoma
  • Disease is refractory, relapsed, or in remission
  • Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Hemoglobin > 8 g/dL
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 50,000/mm^3

Hepatic

  • Bilirubin ≤ 2.0 mg/dL
  • SGOT or SGPT ≤ 2.5 times normal
  • No history of severe hepatic dysfunction

Renal

  • Creatinine ≤ 2.0 mg/dL OR
  • Creatinine clearance ≥ 60 mL/min
  • No uncompensated major adrenal dysfunction
  • BUN < 1.5 times normal

Cardiovascular

  • No severe cardiac dysfunction
  • No major heart disease
  • LVEF ≥ 50% by MUGA
  • No uncontrolled hypertension
  • No congenital or acquired heart disease or cardiac arrhythmias unless cardiac consult and evaluation are done

Pulmonary

  • DLCO ≥ 50% of normal
  • No symptomatic obstructive or restrictive disease

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active infections
  • HIV negative
  • No significant skin breakdown from tumor or other diseases
  • Dental evaluation and teeth cleaning with no potential sources of infection required
  • No uncompensated major thyroid dysfunction

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior stem cell transplantation

Chemotherapy

  • No prior total doxorubicin or daunorubicin dose ≥ 450 mg/m^2 unless endomyocardial biopsy shows < grade 2 drug effect AND ejection fraction ≥ 50% by gated blood pool scan

Endocrine therapy

  • No concurrent hormonal therapy except steroids for adrenal failure, septic shock, or pulmonary toxicity or hormones for non-disease-related conditions (e.g., insulin for diabetes)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

Other trials in United States

About this study

Official title: Immune Consolidation With Activated T Cells Armed With OKT3 x Rituxan (Anti-CD3 x Anti-CD20) Bispecific Antibody (CD20Bi) After Peripheral Blood Stem Cell Transplant for High Risk CD20+ Non-Hodgkin's Lymphomas

RATIONALE: Drugs used in chemotherapy, such as carmustine, etoposide, cytarabine, and melphalan work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving white blood cells, that have been treated in the laboratory with antibodies, may make the transplant work better. Giving combination chemotherapy followed by an autologous stem cell transplant, and white blood cell infusions may be an effective treatment for non-Hodgkin's lymphoma.

PURPOSE: This phase I trial is studying the side effects and best dose of white blood cell infusions when given together with combination chemotherapy, and autologous stem cell transplant in treating patients with non-Hodgkin's lymphoma that has relapsed, is refractory, or is in remission.

Read the detailed description

OBJECTIVES:

  • Determine the toxicity of high-dose combination chemotherapy comprising cyclophosphamide, thiotepa, and carboplatin followed by autologous peripheral blood stem cell transplantation and immunotherapy consolidation therapy comprising anti-CD3 x anti-CD20 bispecific antibody (CD20Bi)-activated T cells (ATC) in patients with non-Hodgkin's lymphoma.
  • Determine the maximum tolerated dose of CD20Bi-ATC in patients treated with this regimen.
  • Determine whether ATC traffic to tumor sites in select patients treated with this regimen.
  • Assess the immune reconstitution of B cells and incidence of infection in patients treated with this regimen.
  • Compare relapse rates and overall survival of patients treated with this regimen with historical controls.

OUTLINE: This is a dose-escalation study of activated T cells.

  • Peripheral blood stem cell (PBSC) mobilization and collection: Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily for 5 days. They then undergo leukaphereses to collect peripheral blood stem cells (PBSC). Some of the lymphocytes are treated in the laboratory to produce anti-CD3 x anti-CD20 bispecific antibody (CD20Bi)-activated T cells (ATC).
  • High-dose chemotherapy and PBSC transplantation: Patients receive carmustine IV on day -7, etoposide IV twice daily and cytarabine IV twice daily on days -6, -5, -4, and -3, and melphalan IV on day -2. Autologous PBSC are reinfused on day 0.
  • Immunotherapy consolidation: Patients receive immunotherapy consolidation comprising CD20Bi-ATC IV over 15-30 minutes starting on day 4, once a week for 4 weeks for a total of four infusions.

Cohorts of 3-6 patients receive escalating doses of CD20Bi-ATC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 12-24 patients will be accrued for this study.

Conditions
Lymphoma
Being tested
therapeutic autologous lymphocytes, carmustine, cytarabine, etoposide, melphalan
Keywords
nodal marginal zone B-cell lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, splenic marginal zone lymphoma, stage III adult Burkitt lymphoma, stage III adult diffuse large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III grade 1 follicular lymphoma
Medical subject headings
Lymphoma, Lymphoma, B-Cell, Marginal Zone, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Follicular

What participants receive

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

  • therapeutic autologous lymphocytesBiological

    Lymphocytes collected by standard apheresis technique either prior to or post stem cell mobilization and collection

  • carmustineDrug

  • cytarabineDrug

  • etoposideDrug

  • melphalanDrug

  • peripheral blood stem cell transplantation (PBSCT)Procedure or surgery

Study groups in NCT00244946
Study groupRoleWhat they receive
Autologous lymphocytes,carmustine,etoposide, melphalan, PBSCTExperimental* minus Day 8 ADMIT for Hydration * minus Day 7 Carmustine 300 mg/m2 x 1 dose * minus Day 6 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr * minus Day 5 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr * minus Day 4 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr * minus Day 3 Etoposide 100 mg/m2 q 12 hr; Cytarabine 100 mg/m2 q 12 hr * minus Day 2 Melphalan 140 mg/m2 x 1 dose * minus Day 1 Day of Rest * Day 0 Transplant
Receives: Biological: therapeutic autologous lymphocytes; Drug: carmustine; Drug: cytarabine; Drug: etoposide; Drug: melphalan; Procedure: peripheral blood stem cell transplantation (PBSCT)

What is being measured

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

  1. To perform a dose escalation trial of ATC armed with CD20Bi immunotherapy after PBSCT to determine the maximum tolerated dose (MTD) of ATC armed with CD20BI.

    This will be the called the maximum tolerated dose. The maximum tolerated dose (MTD) is defined as the dose level below the one at which the side effects are serious enough to prevent an increase in the dose or level of the treatment.

    Measured: When two patienst at any dose levet have their infusion stopped due to side effects.

Secondary outcomes (3)

  1. Evaluate the toxicities of ATC infusions armed with CD20Bi

    Measured: 2 weeks (+/- 7 days), 1, 2, 3, 6 months (+/- 7 days) and 12, and 24 months (+/- one month) after Peripheral Blood Stem Cell Transplants (PBSCT)

  2. Evaluate immune B-cell recovery after ATC infusion

    Measured: 2 weeks (+/- 7 days), 1, 2, 3, 6 months (+/- 7 days) and 12, and 24 months (+/- one month) after Peripheral Blood Stem Cell Transplants (PBSCT)

  3. Evaluate response rates of infusions and compare relapse rates and overall survival to historical controls

    Survival follow-up: 1 year, 3 years, 5 years and 10 years after transplant.

    Measured: 1, 2, 4, 8, 16 and/or 24, 48 and 72 hours post infusion

Timeline

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

  1. First posted27 Oct 2005 (estimated)
  2. Study startMar 2004
  3. Primary completionJan 2010
  4. Study completionMar 2013

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00244946
Sponsor's protocol ID
CDR0000446079
Other IDs
P30CA022453, WSU-2007-023, RWMC-0639446
Status last verified
Mar 2015
First submitted
25 Oct 2005
Last updated
26 Mar 2015
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing therapeutic autologous lymphocytes, carmustine and cytarabine in people with Lymphoma, run by Barbara Ann Karmanos Cancer Institute 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?

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 26 Mar 2015. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

To perform a dose escalation trial of ATC armed with CD20Bi immunotherapy after PBSCT to determine the maximum tolerated dose (MTD) of ATC armed with CD20BI. (time frame: When two patienst at any dose levet have their infusion stopped due to side effects.). 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 NCT00244946.

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 26 Mar 2015.

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