Protocol Summary

Protocol No.: OCR11925

Sponsor Protocol No.: 1101

Study Title
A Multi-Center, Phase III, Randomized Trial of Reduced Intensity (RIC) Conditioning and Transplantation of Double Unrelated Umbilical Cord Blood (dUCB) versus HLA-Haploidentical Related Bone Marrow (haplo-BM) for Patients with Hematologic Malignancies

Principal Investigator(s)
Wingard, John

Hematopoietic cell transplants (HCT) are one treatment option for people with leukemia or lymphoma. Family members, unrelated donors or banked umbilical cordblood units with similar tissue type can be used for HCT. This study will compare the effectiveness of two new types of bone marrow transplants in people with leukemia or lymphoma: one that uses bone marrow donated from family members with only partially matched bone marrow; and, one that uses two partially matched cord blood units.

Reduced intensity conditioning (RIC) blood or marrow transplantation (BMT) has allowed older and less clinically fit patients to receive potentially curative treatment with allogeneic HCT for high risk or advanced hematological malignancies. Patients lacking an HLA-matched sibling may receive a graft from a suitably HLA-matched unrelated donor. However, up to a third of patients will not have an HLA-matched sibling or a suitably matched adult unrelated donor (i.e., no more than a mismatch at a single locus). Even when a suitably matched unrelated donor is identified, data from the National Marrow Donor Program (NMDP) indicate that a median of four months is required to complete searches that result in transplantation; thus, some number of patients succumb to their disease while awaiting identification and evaluation of a suitably matched adult unrelated donor.

Single or dual center studies have shown that partially HLA-mismatched related bone marrow (haplo-BM) and unrelated double umbilical cord blood (dUCB) are valuable sources of donor cells for RIC HCT, thus extending this treatment modality to patients who lack other donors. In order to study the reproducibility, and thus, the wider applicability of these two alternative donor strategies, The Blood and Marrow Transplantation Clinical Trials Network (BMT CTN) conducted two parallel multicenter prospective Phase II clinical trials. These two studies evaluated the safety and efficacy of related haplo-BM (BMT CTN 0603) and dUCB (BMT CTN 0604) transplantation after RIC. Both of these alternative donor approaches produced early results similar to that reported with unrelated donor, and even HLA-matched sibling, HCT. These data demonstrate not only the efficacy of both of these approaches, but also that both can be safely exported from the single center setting. Both haplo-BM and dUCB grafts can be obtained rapidly for greater than 90% of patients lacking an HLA-matched donor. This study will test the hypothesis that progression free survival at two years after RIC haplo-BM transplantation is similar to the progression free survival after RIC dUCB transplantation.

Phase: Phase III

Age Group: Adult

Scope: National

Arm 1:
Haploidentical Bone Marrow Transplant
- Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.

Arm 2:
Double Umbilical Cord Blood Transplant
- Participants will receive a double umbilical cord blood transplant using a reduced intensity conditioning regimen.

Detailed Eligibility
1. Patients 18 to 70 years old
2. Patients must have available both:
- One or more potential related mismatched donors (biologic parent(s) or siblings (full or half) or children).
- At least two potential umbilical cord blood units identified.
3. Patients must have received either:
- At least one cycle of a the following cytotoxic chemotherapy regimen (or regimen of similar intensity) within 3 months of enrollment (1. multiagent chemotherapy, 2. chemotherapy regimens like those that are given as induction or consolidation of acute leukemia, 3. single drug alkylator agent. 4. single agent alemtuzumab or brentuximab vedotin); or,
- Autologous HCT greater than 6 months and less than 2 years prior to enrollment.
4. One of the following disease types:
- ALL in first complete remission (CR1) that is NOT considered favorable-risk as defined by the presence of at least one of the following: Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), other MLL rearrangements; White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL)at diagnosis; Recipient age older than 30 years at diagnosis; Time to CR greater than 4 weeks.
- AML in CR1 that is NOT considered as favorable-risk. Favorable risk is defined as having one of the following: t(8.21) without CKIT mutation, inv(16) without CKIT mutation or t(16;16), normal karyotype with mutated NPM1 and not FLT-IND, normal karyotype with double mutated CEBPA, APL in first molecular remission at end of consolidation.
Acute Leukemias in 2nd or subsequent CR
- Biphenotypic/Undifferentiated/Prolymphocyctic Leukemias in first or subsequent CR, adult T-cell leukemia/lymphoma in first or subsequent CR.
- Burkitt's lymphoma: second or subsequent CR.
- Lymphoma fulfilling the following criteria: Chemotherapy-sensitive (complete or partial response; lymphomas that have failed at least 1 prior regimen of multi-agent chemotherapy and are INELIGIBLE for an autologous transplant; Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at least at least two prior therapies (excluding single agent Rituxan).

Applicable Disease Sites
Lymphoma - Hodgkin
Lymphoma - Non-Hodgkin
Stem Cell Transplant

Participating Institutions
UF Gainesville : Meghan Vazquez

Meghan Vazquez, RN
Phone: +1 352-273-6843


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