InfectionPhase 1/2NCT00046852
Chemotherapy and Peripheral Stem Cell Transplantation Followed By Immunotherapy in Treating Patients With Multiple Myeloma
A Phase 1/2 study testing filgrastim, pneumococcal polyvalent vaccine and therapeutic autologous lymphocytes in people with Infection and Multiple Myeloma and Plasma Cell Neoplasm, run by University of Maryland, Baltimore at 2 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous peripheral stem cell transplantation and immunotherapy may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Infection, Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- filgrastim, pneumococcal polyvalent vaccine and therapeutic autologous lymphocytes
- Type of treatment
- Vaccines, Surgery or procedure
- How many people
- Not given
- Where
- 2 sitesUnited States
- Study dates
- Dec 2001to Feb 2008
- Phase
- Phase 1/2
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of multiple myeloma requiring systemic treatment
- No obvious myelodysplastic changes in the marrow
PATIENT CHARACTERISTICS:
Age
- 18 to 80
Performance status
- ECOG 0-2 (ECOG 3-4 allowed if based solely on bone pain)
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
- No chronic active hepatitis
- No liver cirrhosis
Renal
- Creatinine no greater than 3.0 mg/dL
- No dialysis
Cardiovascular
- LVEF at least 45% unless no evidence of untreated clinically significant functional impairment
Pulmonary
- FEV_1 and FVC at least 50% of predicted
- Total lung capacity at least 50% of predicted
- DLCO at least 50% of predicted
- Mild to moderate pulmonary impairment (lower DLCO) allowed but patients would not receive study carmustine
- Patients unable to complete pulmonary function test due to bone pain or fracture must have high-resolution CT scan of the chest and arterial partial pressure of oxygen greater than 70
Other
- No active infections requiring IV antibiotics
- HIV negative
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- Not specified
Endocrine therapy
- Prior pulse dexamethasone (1-2 courses) allowed
- Concurrent pulse dexamethasone allowed during mobilization therapy
Radiotherapy
- Not specified
Surgery
- Not specified
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Marlene and Stewart Greenebaum Cancer Center, University of Maryland
Baltimore, Maryland, 21201
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104-4283
About this study
Official title: High-Dose Therapy and Autologous Blood Stem Cell Transplantation (ASCT) Followed by Post-Transplant Immunotherapy With Costimulated Autologous T-Cells in Conjunction With Pneumococcal Conjugate Vaccine Immunization for Patients With Multiple Myeloma
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous peripheral stem cell transplantation and immunotherapy may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing.
PURPOSE: Randomized phase I/II trial to study the effectiveness of combining chemotherapy with peripheral stem cell transplantation followed by immunotherapy in treating patients who have multiple myeloma.
Read the detailed description
OBJECTIVES:
- Determine the feasibility of expanding ex vivo autologous T cells and infusing these cells after high-dose chemotherapy and autologous peripheral blood stem cell rescue in patients with multiple myeloma.
- Determine the response rate and progression-free survival of patients who receive anti-CD3/anti-CD28 expanded autologous T cells on either day 14 or day 100 post-transplantation.
- Compare response and survival rates of these patients to historical controls.
- Determine the optimal schedule for pneumococcal conjugate vaccine (PCV) to induce an anti-pneumococcal immune response post-transplantation in these patients.
- Determine whether "vaccine education" of antigen-presenting cells (APCs) in the stem cell graft results in an earlier and/or enhanced immune response than with a graft containing "non-educated" APCs in these patients.
- Determine whether an infusion of T cells presensitized to the PCV and expanded ex vivo contributes to the anti-pneumococcal immune response in these patients.
OUTLINE: This is a randomized, multicenter study.
Patients receive cyclophosphamide IV over 12 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 2. Patients undergo leukapheresis to collect mononuclear cells for autologous T cells (ATCs) and peripheral blood stem cells (PBSCs). ATCs are generated by ex vivo expansion for 8-14 days and selection for CD3+/CD28+ cells.
Patients then receive high-dose therapy comprising carmustine IV over 2 hours on day -2 and melphalan IV over 20 minutes on day -1 or melphalan IV alone on days -2 and -1 (or day -1 only). Autologous PBSCs are reinfused on day 0. Patients also receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
Patients who choose to receive pneumococcal conjugate vaccine (PCV) are randomized to 1 of 4 treatment arms.
- Arm I: Patients receive PCV intramuscularly prior to transplantation (10-14 days before lymphocyte collection) and post-transplantation (1 and 3 months) plus costimulated ATCs IV over 20-60 minutes around day 12-14 post-transplantation.
- Arm II: Patients receive PCV as in arm I but receive ATCs around day 100 post-transplantation.
- Arm III: Patients receive PCV post-transplantation only (at 1 and 3 months) plus ATCs as in arm I.
- Arm IV: Patients receive PCV as in arm III and ATCs as in arm II. Patients who choose not to receive the PCV receive ATCs on about day 12-14 after PBSC transplantation.
All patients are offered standard pneumococcal polysaccharide vaccine at 12 months.
Patients are followed twice weekly until day 60, weekly for 4 months, monthly for 6 months, and then every 3 months thereafter.
PROJECTED ACCRUAL: A total of 16-46 patients will be accrued for this study within 14 months.
- Being tested
- filgrastim, pneumococcal polyvalent vaccine, therapeutic autologous lymphocytes, therapeutic tumor infiltrating lymphocytes, carmustine
- Keywords
- infection, refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
- Medical subject headings
- Infections, Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
pneumococcal polyvalent vaccineBiological
therapeutic autologous lymphocytesBiological
therapeutic tumor infiltrating lymphocytesBiological
carmustineDrug
cyclophosphamideDrug
melphalanDrug
bone marrow ablation with stem cell supportProcedure or surgery
peripheral blood stem cell transplantationProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startDec 2001
- Primary completionNov 2004
- Study completionFeb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfectionStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- University of Maryland Greenebaum Cancer Center
- Investigators
- Aaron P. Rapoport, MD, Study chair, University of Maryland Greenebaum Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00046852
- Sponsor's protocol ID
- CDR0000256870
- Other IDs
- MSGCC-0065, UPCC-6401, NCI-V02-1709
- Status last verified
- Oct 2019
- First submitted
- 3 Oct 2002
- Last updated
- 4 Nov 2019
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-Dose Therapy and Autologous Blood Stem Cell Transplantation (ASCT) Followed by Post-Transplant Immunotherapy With Costimulated Autologous T-Cells in Conjunction With Pneumococcal Conjugate Vaccine Immunization for Patients With Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00046852
- Acronym / sponsor ID
- CDR0000256870
- Keywords
- infection, refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- University of Maryland Greenebaum Cancer Center
- Study start
- Dec 2001
- Primary completion
- Nov 2004 (actual)
- Study completion
- Feb 2008 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous peripheral stem cell transplantation and immunotherapy may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing.
PURPOSE: Randomized phase I/II trial to study the effectiveness of combining chemotherapy with peripheral stem cell transplantation followed by immunotherapy in treating patients who have multiple myeloma.
Detailed description
OBJECTIVES:
- Determine the feasibility of expanding ex vivo autologous T cells and infusing these cells after high-dose chemotherapy and autologous peripheral blood stem cell rescue in patients with multiple myeloma.
- Determine the response rate and progression-free survival of patients who receive anti-CD3/anti-CD28 expanded autologous T cells on either day 14 or day 100 post-transplantation.
- Compare response and survival rates of these patients to historical controls.
- Determine the optimal schedule for pneumococcal conjugate vaccine (PCV) to induce an anti-pneumococcal immune response post-transplantation in these patients.
- Determine whether "vaccine education" of antigen-presenting cells (APCs) in the stem cell graft results in an earlier and/or enhanced immune response than with a graft containing "non-educated" APCs in these patients.
- Determine whether an infusion of T cells presensitized to the PCV and expanded ex vivo contributes to the anti-pneumococcal immune response in these patients.
OUTLINE: This is a randomized, multicenter study.
Patients receive cyclophosphamide IV over 12 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 2. Patients undergo leukapheresis to collect mononuclear cells for autologous T cells (ATCs) and peripheral blood stem cells (PBSCs). ATCs are generated by ex vivo expansion for 8-14 days and selection for CD3+/CD28+ cells.
Patients then receive high-dose therapy comprising carmustine IV over 2 hours on day -2 and melphalan IV over 20 minutes on day -1 or melphalan IV alone on days -2 and -1 (or day -1 only). Autologous PBSCs are reinfused on day 0. Patients also receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
Patients who choose to receive pneumococcal conjugate vaccine (PCV) are randomized to 1 of 4 treatment arms.
- Arm I: Patients receive PCV intramuscularly prior to transplantation (10-14 days before lymphocyte collection) and post-transplantation (1 and 3 months) plus costimulated ATCs IV over 20-60 minutes around day 12-14 post-transplantation.
- Arm II: Patients receive PCV as in arm I but receive ATCs around day 100 post-transplantation.
- Arm III: Patients receive PCV post-transplantation only (at 1 and 3 months) plus ATCs as in arm I.
- Arm IV: Patients receive PCV as in arm III and ATCs as in arm II. Patients who choose not to receive the PCV receive ATCs on about day 12-14 after PBSC transplantation.
All patients are offered standard pneumococcal polysaccharide vaccine at 12 months.
Patients are followed twice weekly until day 60, weekly for 4 months, monthly for 6 months, and then every 3 months thereafter.
PROJECTED ACCRUAL: A total of 16-46 patients will be accrued for this study within 14 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| filgrastim | Biological | – |
| pneumococcal polyvalent vaccine | Biological | – |
| therapeutic autologous lymphocytes | Biological | – |
| therapeutic tumor infiltrating lymphocytes | Biological | – |
| carmustine | Drug | – |
| cyclophosphamide | Drug | – |
| melphalan | Drug | – |
| bone marrow ablation with stem cell support | Procedure or surgery | – |
| peripheral blood stem cell transplantation | Procedure or surgery | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aaron P. Rapoport, MD study chair
University of Maryland Greenebaum Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing filgrastim, pneumococcal polyvalent vaccine and therapeutic autologous lymphocytes in people with Infection and Multiple Myeloma and Plasma Cell Neoplasm, run by University of Maryland, Baltimore 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?
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 4 Nov 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 combined 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.
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?
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.
Where can I read the original study information?
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 4 Nov 2019.