Multiple MyelomaPhase 2NCT00006184
Chemotherapy, Stem Cell Transplantation and Donor and Patient Vaccination for Treatment of Multiple Myeloma
A Phase 2 study testing Myeloma Immunoglobulin Idiotype Vaccine, Bortezomib and Cyclophosphamide in people with Multiple Myeloma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: The mainstay of therapy for newly diagnosed multiple myeloma patients remains systemic chemotherapy. Although partial remissions of up to 60% are obtained with conventional regimens, multiple myeloma is essentially an incurable disease with a median survival of approximately 30 months. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Myeloma Immunoglobulin Idiotype Vaccine, Bortezomib and Cyclophosphamide
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Feb 2001to 12 Jan 2008
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with Immunoglobulin G (IgG) or Immunoglobulin A (IgA) multiple myeloma.
- Patients have siblings.
- Human leukocyte antigen (HLA) typing of recipient and donor(s) initiated.
- Viral antibody screening initiated.
- Patients with IgG or IgA multiple myeloma.
- Patients must have achieved at least a partial remission following initial conventional chemotherapy regimen or after autologous stem cell transplantation. Patients who have undergone tandem autologous stem transplants are eligible if they meet all other eligibility criteria. Patients who have achieved at least a partial remission to initial (primary) conventional chemotherapy will be encouraged to proceed to autologous transplantation, but will also be eligible for this protocol.
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- Patients 18-75 years of age. The upper age limit was chosen as it is felt that the toxicities would exceed potential benefit in this older population.
- Karnofsky performance status greater than or equal to 80%.
- Life expectancy greater than 6 months.
- Left ventricular ejection fraction has to be greater than 50% by either multi-gated acquisition scan (MUGA) or 2-D echo.
- Carbon monoxide diffusing capacity (DLCO) greater than 50% of the expected value when corrected for hemoglobin (Hb)(96).
- Creatinine less than or equal to 1.5 mg/dl and a creatinine clearance greater than or equal to 50 ml/min.
- Direct bilirubin less than or equal to 2.0 mg/dl serum glutamic oxaloacetic transaminase (SGOT) less than 4x top normal.
- M-protein: the concentration in the harvested plasma must be greater than 70% of the total Ig of the corresponding isotype.
- Patients must be human immunodeficiency virus (HIV)-negative. There is the theoretical possibility that the degree of immune suppression associated with the treatment may result in progression of HIV infection. Patients may be Hepatitis B core antigen positive, but surface antigen negative and without evidence of active infection. Patients must be Hepatitis C negative.
- Not pregnant or lactating. Patients of childbearing potential must use an effective method of contraception. The effects of the chemotherapy, the subsequent transplant and the medications used after the transplant are highly likely to be harmful to a fetus. The effects upon breast milk are also unknown and may potentially be harmful to the infant.
- Consenting first degree relative matched at 6/6 or 5/6 HLA antigens, this may include a mismatch at the D locus.
- Ability to give informed consent.
- Age 18-75 years. As the potential cerebrovascular and cardiac complications may potentially increase with age, age 75 has been chosen arbitrarily as the upper age limit. However, if it is determined after initial accrual of patients in this upper age range that this procedure is relatively safe, the age range may be extended.
- No physical contraindications to stem cell donation (i.e. severe atherosclerosis, auto-immune disease, cerebrovascular accident, active malignancy (97). Patients with severe atherosclerosis by history will receive a cardiology consult and be judged eligible on a case by case basis.
- Donors must be HIV-negative, hepatitis B surface antigen (HBsAg-), and Hepatitis C antibody negative. This is to prevent the possible transmission of these infections to the recipient.
- Not pregnant or lactating. Donors of childbearing potential must use an effective method of contraception. The effects of cytokine administration on a fetus are unknown and may be potentially harmful. The effects upon breast milk are also unknown and may potentially be harmful to the infant.
- Normal cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) numbers as defined by Clinical Center standards.
- Ability to give informed consent.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Active Immunization of Sibling Stem Cell Transplant Donors Against Purified Myeloma Protein of the Stem Cell Recipient With Multiple Myeloma in the Setting of Non-Myeloablative, HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation
Background:
The mainstay of therapy for newly diagnosed multiple myeloma patients remains systemic chemotherapy. Although partial remissions of up to 60% are obtained with conventional regimens, multiple myeloma is essentially an incurable disease with a median survival of approximately 30 months.
Read more
Allogeneic stem cell transplantation (SCT) results in a high percentage of complete remissions, but it can be associated with significant treatment-related mortality, which has been primarily attributed to conventional myeloablative transplant regimens.
Recent clinical studies have shown that highly immunosuppressive yet non-myeloablative doses of fludarabine-based chemotherapy can result in alloengraftment. Even with a reduction in treatment related mortality, success with allogeneic SCT is limited by a significant risk of relapse.
Donor immunization with myeloma Id in the setting of a non-myeloablative allogeneic SCT may represent a novel strategy for the treatment of multiple myeloma.
Objectives:
Primary Objectives:
To induce cellular and humoral immunity in allogeneic stem cell donors and recipients against the unique idiotype expressed by the recipient's myeloma.
To determine whether antigen-specific immunity, induced in the stem cell donor, can be passively transferred to the allogeneic SCT recipient in the setting of a non-myeloablative conditioning regimen.
Secondary Objectives:
To evaluate the effect of the Fludarabine-(etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide) EPOCH regimen on host T cell depletion and myeloid depletion prior to allogeneic SCT.
To determine the efficacy of a novel conventional chemotherapy regimen (Fludarabine-EPOCH) in the setting multiple myeloma.
To determine the treatment-related morbidity and mortality of allogeneic stem cell transplantation using a non-myeloablative conditioning regimen in multiple myeloma.
To determine if the re-vaccination of allogeneic stem cell donors with the unique idiotype expressed by the recipient's myeloma will enhance cellular and humoral immunity to patient specific-idiotype prior to lymphocyte donation for the treatment of patients with recurrent or progressive disease after transplantation.
Eligibility:
Patients 18-75 years of age with Immunoglobulin G (IgG) or Immunoglobulin A (IgA) multiple myeloma.
Patients must have achieved at least a partial remission following initial conventional chemotherapy regimen or after autologous stem cell transplantation.
Consenting first degree relative matched at 6/6 or 5/6 human leukocyte antigen (HLA) antigens.
Design:
Phase 2 trial using a non-myeloablative conditioning regimen to reduce treatment-related toxicity.
Recipient will undergo a plasmapheresis to obtain starting material for the isolation of idiotype
protein. Donors would be immunized with an Id vaccine prepared from the patient.
Prior to transplantation patients would receive a conventional chemotherapy regimen which contains agents active in myeloma and is T cell depleting. The allogeneic SCT would be performed with a conditioning regimen consisting of cyclophosphamide and fludarabine. The stem cell source would be blood mobilized with filgrastim. Recipients will be immunized with the Id vaccine following transplantation.
Read the detailed description
Background:
The mainstay of therapy for newly diagnosed multiple myeloma patients remains systemic chemotherapy. Although partial remissions of up to 60% are obtained with conventional regimens, multiple myeloma is essentially an incurable disease with a median survival of approximately 30 months.
Allogeneic stem cell transplantation (SCT) results in a high percentage of complete remissions, but it can be associated with significant treatment-related mortality, which has been primarily attributed to conventional myeloablative transplant regimens.
Recent clinical studies have shown that highly immunosuppressive yet non-myeloablative doses of fludarabine-based chemotherapy can result in allo-engraftment. Even with a reduction in treatment related mortality, success with allogeneic SCT is limited by a significant risk of relapse.
Donor immunization with myeloma Id in the setting of a non-myeloablative allogeneic SCT may represent a novel strategy for the treatment of multiple myeloma.
Objectives:
Primary Objectives:
To induce cellular and humoral immunity in allogeneic stem cell donors and recipients against the unique idiotype expressed by the recipient's myeloma.
To determine whether antigen-specific immunity, induced in the stem cell donor, can be passively transferred to the allogeneic SCT recipient in the setting of a non-myeloablative conditioning regimen.
Secondary Objectives:
To evaluate the effect of the Fludarabine-EPOCH regimen on host T cell depletion and myeloid depletion prior to allogeneic SCT.
To determine the efficacy of a novel conventional chemotherapy regimen (Fludarabine-EPOCH) in the setting multiple myeloma.
To determine the treatment-related morbidity and mortality of allogeneic stem cell transplantation using a non-myeloablative conditioning regimen in multiple myeloma.
To determine if the re-vaccination of allogeneic stem cell donors with the unique idiotype expressed by the recipient's myeloma will enhance cellular and humoral immunity to patient specific-idiotype prior to lymphocyte donation for the treatment of patients with recurrent or progressive disease after transplantation.
Eligibility:
Patients 18-75 years of age with IgG or IgA multiple myeloma.
Patients must have achieved at least a partial remission following initial conventional chemotherapy regimen or after autologous stem cell transplantation.
Consenting first degree relative matched at 6/6 or 5/6 HLA antigens.
Design:
Phase 2 trial using a non-myeloablative conditioning regimen to reduce treatment-related toxicity.
Recipient will undergo a plasmapheresis to obtain starting material for the isolation of idiotype protein. Donors would be immunized with an Id vaccine prepared from the patient.
Prior to transplantation patients would receive a conventional chemotherapy regimen which contains agents active in myeloma and is T cell depleting. The allogeneic SCT would be performed with a conditioning regimen consisting of cyclophosphamide and fludarabine. The stem cell source would be blood mobilized with filgrastim. Recipients will be immunized with the Id vaccine following transplantation.
- Conditions
- Multiple Myeloma
- Being tested
- Myeloma Immunoglobulin Idiotype Vaccine, Bortezomib, Cyclophosphamide, Cyclosporine, Doxorubicin hydrochloride
- Keywords
- Immunoablative, Mobilization, Apheresis, Multiple Myeloma, IgG Multiple Myeloma, IgA Multiple Myeloma
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Myeloma Immunoglobulin Idiotype VaccineDrug
3 subcutaneous (SC) injections of myeloma protein within 10 weeks before stem cell collection the first (week 0), second (week 2), and third injection (week 6) with Id-KLH (0.5 mg SC day 1)
BortezomibDrug
Also called Velcade, PS341
Induction chemotherapy: 1.3 mg/m^2 bolus intravenous injection twice weekly for 2 weeks (days 1, 4, 8, 11) followed by 10 day rest period (day 12-21)
CyclophosphamideDrug
Also called Cytoxan, CTX
Induction chemotherapy: 600 mg/m^2 day 4 Transplant: 1200 mg/m^2 intravenous x 4 days (days -6, -5, -4, -3)
CyclosporineDrug
Also called Sandimmune, Cyclosporin A
Transplant: 2 mg/kg intravenous every 12 hours continuous intravenous or by mouth (PO) until day + 180
Induction chemotherapy: 10 mg/m^2 day continuous intravenous (CIV) days 1-3
EtoposideDrug
Also called Vepesid
Induction chemotherapy: 50 mg/m^2 day continuous intravenous days 1-3
Also called Fludara
Induction chemotherapy: 25 mg/m^2 day intravenous days 1-3 Transplant: 30 mg/m^2 day x 4 days (days -6, -5, -4, -3 )
PrednisoneDrug
Also called Deltasone
60 mg/m^2 day 1-4
Induction chemotherapy: 0.5 mg/m^2 day continuous intravenous days 1-3
MethotrexateDrug
Also called MTX, Methotrexate sodium
Transplant: 5 mg/m^2 intravenous on days +1, +3, +6, +11
GMCSF (granulocyte macrophage colony stimulating factor)Biological
250 mcg/m^2 subcutaneously every day, days 1-4
GCSF (granulocyte colony stimulating factor)Biological
Also called Filgrastim, Neupogen
10 mcg/kg per day subcutaneously daily from day 5 until absolute neutrophil count (ANC) > 1000/ul x 2 days
| Study group | Role | What they receive |
|---|---|---|
| Recipient - Chemotherapy Group | Experimental | Induction chemotherapy with fludarabine, etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone, and granulocyte colony stimulating factor (GCSF) followed by transplant preparative regimen chemotherapy with fludarabine, cyclophosphamide, mesna, cyclosporine, and methotrexate, followed by stem cell infusion and immunization. Receives: Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Doxorubicin hydrochloride; Drug: Etoposide; Drug: Fludarabine phosphate; Drug: Prednisone; Drug: Vincristine Sulfate; Drug: Methotrexate; Biological: GCSF (granulocyte colony stimulating factor) |
| Donor - Vaccine Generation Group | Other | 3 subcutaneous injections of myeloma protein within 10 weeks before stem cell collection. The first (week 0) second (week 2), and third injection (week 6) with Id-KLH (Anti-idiotype-keyhole limpet hemocyanin) (0.5 mg subcutaneous day 1) and Granulocyte macrophage-colony stimulating factor (GM-CSF) (250 mcg/m^2 subcutaneous on days 1-4). Stem cell collection is 4 weeks after the third vaccination. Receives: Drug: Myeloma Immunoglobulin Idiotype Vaccine; Drug: Bortezomib; Biological: GMCSF (granulocyte macrophage colony stimulating factor) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immune Response
Immune cell depletion is defined as immunosuppression of participants T cells prior to transplant measured by cluster of differentiation 4 (CD4) counts (i.e. cells) > 50 cells per ul.Immune T-cell depletion helps to reduce the ability to reject allogeneic cells in participants and is required for engraftment. Engraftment is the body's ability to accept donor cells.
Measured: 105 days
Number of Participants With Adverse Events
Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
Measured: 9 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2000 (estimated)
- Study start8 Feb 2001
- Primary completion12 Jan 2008
- Study completion12 Jan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Ronald Gress, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Claude Sportes, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006184
- Sponsor's protocol ID
- 000201
- Other IDs
- 00-C-0201
- Status last verified
- Sep 2017
- First submitted
- 23 Aug 2000
- Last updated
- 20 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stevenson GT, Stevenson FK. Antibody to a molecularly-defined antigen confined to a tumour cell surface. Nature. 1975 Apr 24;254(5502):714-6. doi: 10.1038/254714a0. No abstract available.
PubMed 47617Stevenson GT, Elliott EV, Stevenson FK. Idiotypic determinants on the surface immunoglobulin of neoplastic lymphocytes: a therapeutic target. Fed Proc. 1977 Aug;36(9):2268-71. No abstract available.
PubMed 69552Miller RA, Maloney DG, Warnke R, Levy R. Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med. 1982 Mar 4;306(9):517-22. doi: 10.1056/NEJM198203043060906. No abstract available.
PubMed 6173751Foglietta M, Neelapu SS, Kwak LW, Jiang Y, Nattamai D, Lee ST, Fowler DH, Sportes C, Gress RE, Steinberg SM, Vence LM, Radvanyi L, Dwyer KC, Qazilbash MH, Bryant RN, Bishop MR. Neoantigen and tumor antigen-specific immunity transferred from immunized donors is detectable early after allogeneic transplantation in myeloma patients. Bone Marrow Transplant. 2013 Feb;48(2):269-77. doi: 10.1038/bmt.2012.132. Epub 2012 Jul 9.
PubMed 22773122Jamshed S, Fowler DH, Neelapu SS, Dean RM, Steinberg SM, Odom J, Bryant K, Hakim F, Bishop MR. EPOCH-F: a novel salvage regimen for multiple myeloma before reduced-intensity allogeneic hematopoietic SCT. Bone Marrow Transplant. 2011 May;46(5):676-81. doi: 10.1038/bmt.2010.173. Epub 2010 Jul 26.
PubMed 20661232
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Active Immunization of Sibling Stem Cell Transplant Donors Against Purified Myeloma Protein of the Stem Cell Recipient With Multiple Myeloma in the Setting of Non-Myeloablative, HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00006184
- Acronym / sponsor ID
- 000201
- Conditions
- Multiple Myeloma
- Keywords
- Immunoablative, Mobilization, Apheresis, Multiple Myeloma, IgG Multiple Myeloma, IgA Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 8 Feb 2001 (actual)
- Primary completion
- 12 Jan 2008 (actual)
- Study completion
- 12 Jan 2008 (actual)
- First posted
- 24 Aug 2000 (estimated)
- Results
- Posted 24 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
The mainstay of therapy for newly diagnosed multiple myeloma patients remains systemic chemotherapy. Although partial remissions of up to 60% are obtained with conventional regimens, multiple myeloma is essentially an incurable disease with a median survival of approximately 30 months.
Allogeneic stem cell transplantation (SCT) results in a high percentage of complete remissions, but it can be associated with significant treatment-related mortality, which has been primarily attributed to conventional myeloablative transplant regimens.
Recent clinical studies have shown that highly immunosuppressive yet non-myeloablative doses of fludarabine-based chemotherapy can result in alloengraftment. Even with a reduction in treatment related mortality, success with allogeneic SCT is limited by a significant risk of relapse.
Donor immunization with myeloma Id in the setting of a non-myeloablative allogeneic SCT may represent a novel strategy for the treatment of multiple myeloma.
Objectives:
Primary Objectives:
To induce cellular and humoral immunity in allogeneic stem cell donors and recipients against the unique idiotype expressed by the recipient's myeloma.
To determine whether antigen-specific immunity, induced in the stem cell donor, can be passively transferred to the allogeneic SCT recipient in the setting of a non-myeloablative conditioning regimen.
Secondary Objectives:
To evaluate the effect of the Fludarabine-(etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide) EPOCH regimen on host T cell depletion and myeloid depletion prior to allogeneic SCT.
To determine the efficacy of a novel conventional chemotherapy regimen (Fludarabine-EPOCH) in the setting multiple myeloma.
To determine the treatment-related morbidity and mortality of allogeneic stem cell transplantation using a non-myeloablative conditioning regimen in multiple myeloma.
To determine if the re-vaccination of allogeneic stem cell donors with the unique idiotype expressed by the recipient's myeloma will enhance cellular and humoral immunity to patient specific-idiotype prior to lymphocyte donation for the treatment of patients with recurrent or progressive disease after transplantation.
Eligibility:
Patients 18-75 years of age with Immunoglobulin G (IgG) or Immunoglobulin A (IgA) multiple myeloma.
Patients must have achieved at least a partial remission following initial conventional chemotherapy regimen or after autologous stem cell transplantation.
Consenting first degree relative matched at 6/6 or 5/6 human leukocyte antigen (HLA) antigens.
Design:
Phase 2 trial using a non-myeloablative conditioning regimen to reduce treatment-related toxicity.
Recipient will undergo a plasmapheresis to obtain starting material for the isolation of idiotype
protein. Donors would be immunized with an Id vaccine prepared from the patient.
Prior to transplantation patients would receive a conventional chemotherapy regimen which contains agents active in myeloma and is T cell depleting. The allogeneic SCT would be performed with a conditioning regimen consisting of cyclophosphamide and fludarabine. The stem cell source would be blood mobilized with filgrastim. Recipients will be immunized with the Id vaccine following transplantation.
Detailed description
Background:
The mainstay of therapy for newly diagnosed multiple myeloma patients remains systemic chemotherapy. Although partial remissions of up to 60% are obtained with conventional regimens, multiple myeloma is essentially an incurable disease with a median survival of approximately 30 months.
Allogeneic stem cell transplantation (SCT) results in a high percentage of complete remissions, but it can be associated with significant treatment-related mortality, which has been primarily attributed to conventional myeloablative transplant regimens.
Recent clinical studies have shown that highly immunosuppressive yet non-myeloablative doses of fludarabine-based chemotherapy can result in allo-engraftment. Even with a reduction in treatment related mortality, success with allogeneic SCT is limited by a significant risk of relapse.
Donor immunization with myeloma Id in the setting of a non-myeloablative allogeneic SCT may represent a novel strategy for the treatment of multiple myeloma.
Objectives:
Primary Objectives:
To induce cellular and humoral immunity in allogeneic stem cell donors and recipients against the unique idiotype expressed by the recipient's myeloma.
To determine whether antigen-specific immunity, induced in the stem cell donor, can be passively transferred to the allogeneic SCT recipient in the setting of a non-myeloablative conditioning regimen.
Secondary Objectives:
To evaluate the effect of the Fludarabine-EPOCH regimen on host T cell depletion and myeloid depletion prior to allogeneic SCT.
To determine the efficacy of a novel conventional chemotherapy regimen (Fludarabine-EPOCH) in the setting multiple myeloma.
To determine the treatment-related morbidity and mortality of allogeneic stem cell transplantation using a non-myeloablative conditioning regimen in multiple myeloma.
To determine if the re-vaccination of allogeneic stem cell donors with the unique idiotype expressed by the recipient's myeloma will enhance cellular and humoral immunity to patient specific-idiotype prior to lymphocyte donation for the treatment of patients with recurrent or progressive disease after transplantation.
Eligibility:
Patients 18-75 years of age with IgG or IgA multiple myeloma.
Patients must have achieved at least a partial remission following initial conventional chemotherapy regimen or after autologous stem cell transplantation.
Consenting first degree relative matched at 6/6 or 5/6 HLA antigens.
Design:
Phase 2 trial using a non-myeloablative conditioning regimen to reduce treatment-related toxicity.
Recipient will undergo a plasmapheresis to obtain starting material for the isolation of idiotype protein. Donors would be immunized with an Id vaccine prepared from the patient.
Prior to transplantation patients would receive a conventional chemotherapy regimen which contains agents active in myeloma and is T cell depleting. The allogeneic SCT would be performed with a conditioning regimen consisting of cyclophosphamide and fludarabine. The stem cell source would be blood mobilized with filgrastim. Recipients will be immunized with the Id vaccine following transplantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Recipient - Chemotherapy Group | Experimental | Drug: Bortezomib, Drug: Cyclophosphamide, Drug: Cyclosporine, Drug: Doxorubicin hydrochloride, Drug: Etoposide, Drug: Fludarabine phosphate, Drug: Prednisone, Drug: Vincristine Sulfate, Drug: Methotrexate, Biological: GCSF (granulocyte colony stimulating factor)Induction chemotherapy with fludarabine, etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone, and granulocyte colony stimulating factor (GCSF) followed by transplant preparative regimen chemotherapy with fludarabine, cyclophosphamide, mesna, cyclosporine, and methotrexate, followed by stem cell infusion and immunization. |
| Donor - Vaccine Generation Group | Other | Drug: Myeloma Immunoglobulin Idiotype Vaccine, Drug: Bortezomib, Biological: GMCSF (granulocyte macrophage colony stimulating factor)3 subcutaneous injections of myeloma protein within 10 weeks before stem cell collection. The first (week 0) second (week 2), and third injection (week 6) with Id-KLH (Anti-idiotype-keyhole limpet hemocyanin) (0.5 mg subcutaneous day 1) and Granulocyte macrophage-colony stimulating factor (GM-CSF) (250 mcg/m^2 subcutaneous on days 1-4). Stem cell collection is 4 weeks after the third vaccination. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Patients with Immunoglobulin G (IgG) or Immunoglobulin A (IgA) multiple myeloma.
- Patients have siblings.
- Human leukocyte antigen (HLA) typing of recipient and donor(s) initiated.
- Viral antibody screening initiated.
- Patients with IgG or IgA multiple myeloma.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Myeloma Immunoglobulin Idiotype Vaccine3 subcutaneous (SC) injections of myeloma protein within 10 weeks before stem cell collection the first (week 0), second (week 2), and third injection (week 6) with Id-KLH (0.5 mg SC day 1) | Drug | Donor - Vaccine Generation Group |
| BortezomibAlso: Velcade, PS341Induction chemotherapy: 1.3 mg/m^2 bolus intravenous injection twice weekly for 2 weeks (days 1, 4, 8, 11) followed by 10 day rest period (day 12-21) | Drug | Donor - Vaccine Generation Group, Recipient - Chemotherapy Group |
| CyclophosphamideAlso: Cytoxan, CTXInduction chemotherapy: 600 mg/m^2 day 4 Transplant: 1200 mg/m^2 intravenous x 4 days (days -6, -5, -4, -3) | Drug | Recipient - Chemotherapy Group |
| CyclosporineAlso: Sandimmune, Cyclosporin ATransplant: 2 mg/kg intravenous every 12 hours continuous intravenous or by mouth (PO) until day + 180 | Drug | Recipient - Chemotherapy Group |
| Doxorubicin hydrochlorideInduction chemotherapy: 10 mg/m^2 day continuous intravenous (CIV) days 1-3 | Drug | Recipient - Chemotherapy Group |
| EtoposideAlso: VepesidInduction chemotherapy: 50 mg/m^2 day continuous intravenous days 1-3 | Drug | Recipient - Chemotherapy Group |
| Fludarabine phosphateAlso: FludaraInduction chemotherapy: 25 mg/m^2 day intravenous days 1-3 Transplant: 30 mg/m^2 day x 4 days (days -6, -5, -4, -3 ) | Drug | Recipient - Chemotherapy Group |
| PrednisoneAlso: Deltasone60 mg/m^2 day 1-4 | Drug | Recipient - Chemotherapy Group |
| Vincristine SulfateInduction chemotherapy: 0.5 mg/m^2 day continuous intravenous days 1-3 | Drug | Recipient - Chemotherapy Group |
| MethotrexateAlso: MTX, Methotrexate sodiumTransplant: 5 mg/m^2 intravenous on days +1, +3, +6, +11 | Drug | Recipient - Chemotherapy Group |
| GMCSF (granulocyte macrophage colony stimulating factor)250 mcg/m^2 subcutaneously every day, days 1-4 | Biological | Donor - Vaccine Generation Group |
| GCSF (granulocyte colony stimulating factor)Also: Filgrastim, Neupogen10 mcg/kg per day subcutaneously daily from day 5 until absolute neutrophil count (ANC) > 1000/ul x 2 days | Biological | Recipient - Chemotherapy Group |
Primary outcome
Immune Response
Time frame: 105 days
Immune cell depletion is defined as immunosuppression of participants T cells prior to transplant measured by cluster of differentiation 4 (CD4) counts (i.e. cells) > 50 cells per ul.Immune T-cell depletion helps to reduce the ability to reject allogeneic cells in participants and is required for engraftment. Engraftment is the body's ability to accept donor cells.
Number of Participants With Adverse Events
Time frame: 9 years
Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 47617Stevenson GT, Stevenson FK. Antibody to a molecularly-defined antigen confined to a tumour cell surface. Nature. 1975 Apr 24;254(5502):714-6. doi: 10.1038/254714a0. No abstract available.
- Background: PubMed 69552Stevenson GT, Elliott EV, Stevenson FK. Idiotypic determinants on the surface immunoglobulin of neoplastic lymphocytes: a therapeutic target. Fed Proc. 1977 Aug;36(9):2268-71. No abstract available.
- Background: PubMed 6173751Miller RA, Maloney DG, Warnke R, Levy R. Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med. 1982 Mar 4;306(9):517-22. doi: 10.1056/NEJM198203043060906. No abstract available.
- Results publication: PubMed 22773122Foglietta M, Neelapu SS, Kwak LW, Jiang Y, Nattamai D, Lee ST, Fowler DH, Sportes C, Gress RE, Steinberg SM, Vence LM, Radvanyi L, Dwyer KC, Qazilbash MH, Bryant RN, Bishop MR. Neoantigen and tumor antigen-specific immunity transferred from immunized donors is detectable early after allogeneic transplantation in myeloma patients. Bone Marrow Transplant. 2013 Feb;48(2):269-77. doi: 10.1038/bmt.2012.132. Epub 2012 Jul 9.
- Derived from this study: PubMed 20661232Jamshed S, Fowler DH, Neelapu SS, Dean RM, Steinberg SM, Odom J, Bryant K, Hakim F, Bishop MR. EPOCH-F: a novel salvage regimen for multiple myeloma before reduced-intensity allogeneic hematopoietic SCT. Bone Marrow Transplant. 2011 May;46(5):676-81. doi: 10.1038/bmt.2010.173. Epub 2010 Jul 26.
- Individual participant dataSharing planned: No
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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.
Claude Sportes, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Myeloma Immunoglobulin Idiotype Vaccine, Bortezomib and Cyclophosphamide in people with Multiple Myeloma, run by National Cancer Institute (NCI) 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 24 inclusion and 0 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 20 Oct 2017. 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 24 Jan 2013). 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?
Immune Response (time frame: 105 days). The study lists 2 primary outcomes in all. 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 NCT00006184, which also lists 5 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 20 Oct 2017.