Multiple Myeloma Clinical Trial
Official title:
Pilot Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Matched Unrelated Double Cord Blood Transplant for the Treatment of Leukemias, Lymphomas, and Pre-Malignant Blood Disorders
Background:
- Allogeneic stem cell transplantation (SCT) has been used to treat many kinds of cancer
or pre-cancerous conditions that develop in blood or immune system cells. Umbilical cord
blood transplantation (UCBT) is a type of allogeneic transplant that is used when none
of a patient s siblings are a match and an acceptable match cannot be identified from
one of the bone marrow registries. Prior to receiving the cord blood stem cells, large
doses of chemotherapy drugs and/or radiation have been traditionally used to eliminate
most of the cancerous or abnormal cells from the recipient s system, along with most of
his or her own stem cells and immune cells. Donor stem cells then replace the recipient
s stem cells in the bone marrow, restoring normal blood production and immunity. In this
way, an allogeneic SCT provides not only new blood cells but an entire new immune
system.
- In the past, allogeneic SCT was performed with very high doses of chemotherapy and/or
radiation to get rid of as much of the recipient s cancer as possible and prevent
rejection of the treatment. However, intensive chemotherapy or radiation can cause
serious side effects, including death. A newer method uses smaller, less toxic doses of
chemotherapy and/or radiation before allogeneic SCT. In these reduced-intensity stem
cell transplants, the recipient s stem cells and immunity are not completely eliminated,
but they are weakened enough to help prevent the donor s cells from being rejected.
Objectives:
- To study the safety and effectiveness of reduced-intensity stem cell transplants given with
immune-depleting chemotherapy and umbilical cord blood provided by an unrelated donor.
Eligibility:
- Individuals between 18 and 69 years of age who have been diagnosed with any of a number
of cancerous and pre-cancerous blood conditions, including lymphoma and leukemia.
- Participants must not have a potential donor sibling or a readily available unrelated
donor identified through one of the bone marrow donor registries.
Design:
- Patients will be matched with at least two umbilical cords with an acceptable cell dose.
The two frozen umbilical cord blood units will be sent to the NIH prior to the date of
transplant.
- Patients will receive one, two, or three cycles of chemotherapy (based on the type of
disease) to treat the disease and to weaken the immune system. Patients who already have
a weakened immune system from other treatments will not receive this round of
chemotherapy.
- Patients will then receive 4 days of reduced-intensity transplant chemotherapy (also
called the conditioning regimen ) to prepare for the transplant.
- Two days after transplant chemotherapy, patients will receive the transplant, with the
two umbilical cords infused one after the other on the same day. Patients will receive
additional treatment to prevent complications.
- Patients will remain in the hospital for 4 to 6 weeks after the transplant, and will be
discharged for outpatient treatment when the study doctors deem it appropriate.
- Patients will continue on medications at home to lower the risk of complications and
infections, and will visit the NIH clinic regularly for the first 6 months after the
transplant, and then less often for at least 5 years afterward.
Background:
The major limitations of umbilical cord blood transplantation (UCBT) in adults are graft
rejection and delayed engraftment leading to increased infection-related morbidity and
treatment related mortality (TRM). To increase engraftment rates while at the same time
enhancing graft-versus-tumor effect, previous studies within our institution have employed
the strategy of targeted immune depletion (TID). The goal of TID is to use T-cell suppressive
chemotherapy prior to the conditioning regimen to treat the patient s disease while
concurrently depleting host T-cells. This has lead to earlier complete donor chimerism in the
setting of allogeneic sibling donor and matched unrelated donor transplantation. Our aim in
the current protocol is to extend the strategy of TID to reduced-intensity UCBT, with the
goal of more rapid engraftment, leading to decreased TRM and increased overall survival. Our
intention is to investigate this approach in the setting of double cord blood transplant in
adults in a pilot manner.
Objectives:
- The primary objective of this study is to see whether targeted immune depletion can
shorten the time to neutrophil recovery and improve the cord blood engraftment rate as
measured by ANC greater than or equal to 500 x 3 and at least partial donor chimerism
(10-90%).
- Secondary objectives include further assessment of hematopoetic recovery, treatment
related morbidity including infections and acute and chronic GVHD, TRM, progression free
and overall survival, further assessment of immune reconstitution, and study of
engraftment kinetics as they apply to prediction of which of the two transplanted cords
will engraft in relation to cell dose, CD34+ dose, HLA-match, and other experimental
variables.
Eligibility:
- Adults (18-69 years) with advanced or high-risk hematologic malignancies including AML,
ALL, MDS, CLL, NHL, HL, CML, multiple myeloma, and MPD who lack a readily available
HLA-matched sibling or greater than or equal to 7/8 HLA-matched unrelated donor.
Patients must have life expectancy of at least 3 months, ECOG less than or equal to 2,
and relatively normal major organ functions.
- Patients must have two partially HLA-matched UCB units. Units must be HLA-matched at
HLA-A and B (intermediate resolution molecular typing) and DRB1 (high resolution
molecular typing) 4-6/6 with the recipient and 4-6/6 with each other. Each unit must
contain a minimum precryopreserved, nucleated cell dose of 1.5 x 10(7) per kilogram.
Design:
- This is a Pilot study of TID in the setting of reduced-intensity double cord blood
transplant in adults.
- Patients will receive disease-specific induction chemotherapy (EPOCH-F/R or FLAG) prior
to transplant for disease control and immune depletion.
- All patients will receive an identical conditioning regimen consisting of
cyclophosphamide 1200 mg/m(2)/day IV for 4 days and fludarabine 30 mg/m(2)/day for 4
days.
- A maximum of 13 patients will be transplanted in the initial part of this pilot study.
If no stopping rules are reached, the study will be expanded to allow the
transplantation of an additional 12 patients (a total of 25 patients).
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