Multiple MyelomaPhase 1NCT00854139
Combined Bone Marrow Transplantation (BMT) and Renal Transplant for Multiple Myeloma (MM) With End Stage Renal Disease (ESRD)
A Phase 1 study testing Cyclophosphamide, anti-thymocyte globulin, Kidney transplant and Thymic irradiation in people with Multiple Myeloma and End Stage Renal Disease, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The primary objective is to cure multiple myeloma with less toxic allogeneic bone marrow transplantation while inducing renal allograft tolerance through mixed chimerism in patients with end stage renal failure and multiple myeloma Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Myeloma, End Stage Renal Disease
- What is being tested?
- Cyclophosphamide, anti-thymocyte globulin, Kidney transplant and Thymic irradiation
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2001to Jul 2014
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Recipient Inclusion Criteria
- Participants with end-stage renal failure due to or in association with greater than or equal to stage II multiple myeloma
- Males or females 18 - 65 years of age.
- Participants must have an HLA-matched or one of six HLA A, B, or DR antigen-mismatched related donor, with high resolution molecular DR allele determination.
- Men and women of reproductive potential must agree to use a reliable method of birth control during the treatment, and women should do so for a period of 2 years following the transplant.
- Participants should be on dialysis or have a CrCl <20 ml/min.
- Participants must receive medical clearance by a cardiologist prior to conditioning for transplant.
- Life expectancy greater than or equal to 6 months.
- Recipient ability to understand and provide informed consent.
Recipient Exclusion Criteria:
- Evidence of active infection as defined by: a) clinical syndrome consistent with viral or bacterial infection (e.g., influenza, URI, UTI) or b) fever with a clinical site of infection identified, or c) microbiologically documented infection, including, but not limited to, bacteremia or septicemia.
- Participation in other investigational drug use at the time of enrollment.
- Contraindication to therapy with any one of the proposed agents (e.g., history of allergy to horse serum in ATG).
- Serologic positivity to HIV, HCV, or HbsAg positivity.
- Women of childbearing age in whom adequate contraception cannot be maintained.
- Malignancy within the past two years other than multiple myeloma, excluding basal cell carcinoma of the skin and carcinoma in situ of the cervix.
- AST/ALT > 3 x normal or bilirubin > 1.5 x normal (unless due to Gilbert's syndrome).
- Pregnancy or uncontrolled serious medical illness not related to underlying myeloma.
- Cardiac ejection fraction < 40% by echocardiogram; individual assessment if ejection fraction between 40% and 50%.
- FEV1 < 50% predicted or corrected DLCO < 50% predicted.
- ABO blood group incompatibility in the host-vs-graft direction.
Donor Inclusion Criteria:
- HLA-matched or one of six HLA A, B, or DR antigen-mismatched related male or female donor 18-65 years of age.
- ECOG performance status 0 or 1.
- Excellent health per conventional pre-donor history (medical and psychosocial evaluation).
- Acceptable laboratory parameters (hematology in normal or near-normal range; liver function < 2 times the upper limit of normal and normal creatinine).
- Compatible ABO blood group.
- Negative donor lymphocyte crossmatch.
- No positive testing for viral infection (HbsAg, HIV, HCV, HTLV-1).
- Cardiac/Pulmonary evaluation within normal limits (CXR, EKG).
- Donor ability to understand and provide informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Combined HLA-matched Bone Marrow and Kidney Transplantation for Multiple Myeloma With Renal Failure
The primary objective is to cure multiple myeloma with less toxic allogeneic bone marrow transplantation while inducing renal allograft tolerance through mixed chimerism in patients with end stage renal failure and multiple myeloma
Read the detailed description
The induction of transplantation tolerance involves the specific elimination of the immune response to the transplant but not to other antigens. In the realm of kidney transplantation, tolerance means that the recipient is unable to detect the donor transplant kidney as foreign, and therefore the recipient is unable to reject the kidney. Donor bone marrow engraftment leads to kidney graft tolerance in animal models. Renal failure is a major complication of multiple myeloma, a plasma cell malignancy for which the only known cure is allogeneic bone marrow transplantation. Standard bone marrow transplantation is associated with frequent toxicity in patients with multiple myeloma, and is generally no considered an option for those patients with end stage renal disease. Myeloma patients are excluded from conventional renal transplantation protocols because of their underlying malignancy. A less toxic bone marrow transplantation protocol, combined with renal transplantation, could provide an opportunity for cure of the myeloma and correction of ESRD in patients with this disease. In addition, successful marrow engraftment may be expected to lead to a state of tolerance. Successful implementation of tolerance would be a major benefit to transplant recipients. The significance of developing tolerance is that the patient would be spared the disabling complications of indefinite immunosuppression, which include infections, cataracts, osteoporosis, diabetes, atherosclerosis, hypertension, and malignancy
- Conditions
- Multiple Myeloma, End Stage Renal Disease
- Being tested
- Cyclophosphamide, anti-thymocyte globulin, Kidney transplant, Thymic irradiation, Bone marrow transplant from a related donor
- Keywords
- Multiple myeloma, Renal failure, Kidney transplant
- Medical subject headings
- Multiple Myeloma, Kidney Failure, Chronic, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyclophosphamide, anti-thymocyte globulinDrug
Also called Cyclosporine
Cyclophosphamide 60 mg/kg IV on Day -5, -4 Anti-thymocyte globulin 20 mg/kg IV on Day -1, Day +1, +3, +5
Cyclosporine starting on Day -1 at 5 mg/kg daily I.V. and reduced to 3 mg/kg on Day +4, and adjusted to provide a trough whole blood concentration of 250-400 ng/mL. The route of administration will be changed to oral as soon as the patient is able to tolerate oral medications
Kidney transplantProcedure or surgery
On Day 0 the renal transplant is performed according to standard surgical techniques, preferably using an iliac fossa, extraperitoneal approach
Thymic irradiationRadiation
Thymic irradiation 7 Gy on Day -1
Bone marrow transplant from a related donorProcedure or surgery
- Donor bone marrow (> 2 x 108 nucleated cells/kg of recipient body weight) is prepared for infusion according to the standard procedure at the medical center. A total of 15,000 Units of heparin is mixed with the marrow, which is infused at a rate of 300-500 cc/hr. The infusion begins in the operating room as soon as the vascular anastomosis of the renal allograft has been completed. Protamine, 25 mg, is administered I.V. after completion of the first half of the bone marrow infusion. If a partial thromboplastin time measured after completion of the marrow infusion is > 60 seconds, the protamine treatment shall be repeated
| Study group | Role | What they receive |
|---|---|---|
| Bone marrow and renal transplant | Experimental | Cyclophosphamide, anti-thymocyte globulin, thymic irradiation conditioning and kidney transplant and bone marrow transplant from a related donor for patients with multiple myeloma and end stage renal disease with cyclosporine for graft versus host disease prophylaxis Receives: Drug: Cyclophosphamide, anti-thymocyte globulin; Procedure: Kidney transplant; Radiation: Thymic irradiation; Procedure: Bone marrow transplant from a related donor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Remission status of multiple myeloma
Measured: 3 years
Renal allograft acceptance and ability to discontinue immunosuppressive therapy
Measured: 3 years
Secondary outcomes (3)
Graft versus host disease (GVHD)
Measured: 3 years
Opportunistic infections
Measured: 3 years
T cell recovery and immune reconstitution
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2009 (estimated)
- Study startAug 2001
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thomas Spitzer, Massachusetts General Hospital
- Investigators
- Thomas R Spitzer, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00854139
- Sponsor's protocol ID
- NKD01
- Status last verified
- Mar 2020
- First submitted
- 27 Feb 2009
- Last updated
- 4 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined HLA-matched Bone Marrow and Kidney Transplantation for Multiple Myeloma With Renal Failure
- ClinicalTrials.gov ID
- NCT00854139
- Acronym / sponsor ID
- NKD01
- Conditions
- Multiple Myeloma, End Stage Renal Disease
- Keywords
- Multiple myeloma, Renal failure, Kidney transplant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Aug 2001
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 3 Mar 2009 (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.
The primary objective is to cure multiple myeloma with less toxic allogeneic bone marrow transplantation while inducing renal allograft tolerance through mixed chimerism in patients with end stage renal failure and multiple myeloma
Detailed description
The induction of transplantation tolerance involves the specific elimination of the immune response to the transplant but not to other antigens. In the realm of kidney transplantation, tolerance means that the recipient is unable to detect the donor transplant kidney as foreign, and therefore the recipient is unable to reject the kidney. Donor bone marrow engraftment leads to kidney graft tolerance in animal models. Renal failure is a major complication of multiple myeloma, a plasma cell malignancy for which the only known cure is allogeneic bone marrow transplantation. Standard bone marrow transplantation is associated with frequent toxicity in patients with multiple myeloma, and is generally no considered an option for those patients with end stage renal disease. Myeloma patients are excluded from conventional renal transplantation protocols because of their underlying malignancy. A less toxic bone marrow transplantation protocol, combined with renal transplantation, could provide an opportunity for cure of the myeloma and correction of ESRD in patients with this disease. In addition, successful marrow engraftment may be expected to lead to a state of tolerance. Successful implementation of tolerance would be a major benefit to transplant recipients. The significance of developing tolerance is that the patient would be spared the disabling complications of indefinite immunosuppression, which include infections, cataracts, osteoporosis, diabetes, atherosclerosis, hypertension, and malignancy
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bone marrow and renal transplant | Experimental | Drug: Cyclophosphamide, anti-thymocyte globulin, Procedure: Kidney transplant, Radiation: Thymic irradiation, Procedure: Bone marrow transplant from a related donorCyclophosphamide, anti-thymocyte globulin, thymic irradiation conditioning and kidney transplant and bone marrow transplant from a related donor for patients with multiple myeloma and end stage renal disease with cyclosporine for graft versus host disease prophylaxis |
Who may qualify
- Ages
- 18 to 65 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 |
|---|---|---|
| Cyclophosphamide, anti-thymocyte globulinAlso: CyclosporineCyclophosphamide 60 mg/kg IV on Day -5, -4 Anti-thymocyte globulin 20 mg/kg IV on Day -1, Day +1, +3, +5 Cyclosporine starting on Day -1 at 5 mg/kg daily I.V. and reduced to 3 mg/kg on Day +4, and adjusted to provide a trough whole blood concentration of 250-400 ng/mL. The route of administration will be changed to oral as soon as the patient is able to tolerate oral medications | Drug | Bone marrow and renal transplant |
| Kidney transplantOn Day 0 the renal transplant is performed according to standard surgical techniques, preferably using an iliac fossa, extraperitoneal approach | Procedure or surgery | Bone marrow and renal transplant |
| Thymic irradiationThymic irradiation 7 Gy on Day -1 | Radiation | Bone marrow and renal transplant |
| Bone marrow transplant from a related donor• Donor bone marrow (> 2 x 108 nucleated cells/kg of recipient body weight) is prepared for infusion according to the standard procedure at the medical center. A total of 15,000 Units of heparin is mixed with the marrow, which is infused at a rate of 300-500 cc/hr. The infusion begins in the operating room as soon as the vascular anastomosis of the renal allograft has been completed. Protamine, 25 mg, is administered I.V. after completion of the first half of the bone marrow infusion. If a partial thromboplastin time measured after completion of the marrow infusion is > 60 seconds, the protamine treatment shall be repeated | Procedure or surgery | Bone marrow and renal transplant |
Primary outcome
Remission status of multiple myeloma
Time frame: 3 years
Renal allograft acceptance and ability to discontinue immunosuppressive therapy
Time frame: 3 years
3 secondary outcomes
Graft versus host disease (GVHD)
Time frame: 3 years
Opportunistic infections
Time frame: 3 years
T cell recovery and immune reconstitution
Time frame: 3 years
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 Mar 2020.
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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.
Thomas R Spitzer, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cyclophosphamide, anti-thymocyte globulin, Kidney transplant and Thymic irradiation in people with Multiple Myeloma and End Stage Renal Disease, run by Massachusetts General Hospital 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 4 Mar 2020. 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?
Remission status of multiple myeloma (time frame: 3 years). 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?
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 Mar 2020.