Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Phase 3, Randomized Trial of RIC & Transplantation of dUCB vs Haplo for Patients w Hem Malignancies

Protocol: BMT-CTN1101

Full 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) for Patients with Hematologic Malignancies

Study Objective

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.

Are you eligible?

Inclusion Criteria:

Patients 18 to 70 years old

Patients must have available both: a)One or more potential related mismatched donors

(biologic parent(s) or siblings (full or half) or children). At least low resolution

DNA based human leukocyte antigen (HLA) typing at HLA-A, -B, and -DRB1 for potential

haploidentical sibling donors is required. b)At least two potential umbilical cord

blood units identified. Each unit must have a minimum of 1.5 x 10^7/kg

pre-cryopreserved total nucleated cell dose. For non-red blood cell depleted units,

the minimum pre-cryopreserved total nucleated cell dose of each unit must be at least

2.0 x 10^7/kg. Units must be HLA matched at a minimum of 4/6 to the recipient at

HLA-A, HLA-B (at low resolution using DNA based typing) and HLA-DRB1 (at high

resolution using DNA based typing). Confirmatory typing is not required for

randomization.

Acute Lymphoblastic Leukemia (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 Mixed

Lineage Leukemia (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

Acute Myelogeneous Leukemia (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, Acute promyelocytic

leukemia (APL) in first molecular remission at end of consolidation

Acute Leukemias in 2nd or subsequent CR

Biphenotypic/Undifferentiated/Prolymphocytic 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 (at least stable

disease lymphomas that have failed at least 1 prior regimen of multi-agent

chemotherapy and are INELIGIBLE for an autologous transplant. Patients with chronic

lymphocytic leukemia (CLL) are not eligible regardless of disease status.

Performance status: Karnofsky score greater than or equal to 70%.

Additional Patient Inclusion Criteria for Conditioning:

Patients with Adequate Physical Function as Measured by: a. Cardiac: Left ventricular

ejection fraction at rest must be greater than or equal to 40%, or shortening

fraction less than 25%; b. Hepatic: Bilirubin less than or equal to 2.5 mg/dL, except

for patients with Gilbert's syndrome or hemolysis. Alanine aminotransferase (ALT),

aspartate aminotransferase (AST), and Alkaline Phosphatase less than 5 x upper limit

of normal; c. Renal: Serum creatinine within normal range, or if serum creatinine

outside normal range, then renal function (measured or estimated creatinine clearance

or GFR)greater than 40 mL/min/1.73m^; d. Pulmonary: Diffusing capacity of the lung

for carbon monoxide (DLCO) (corrected for hemoglobin), forced expiratory volume in

one second (FEV1), and forced vital capacity (FVC) greater than 50% predicted;

Additional Patient Inclusion Criteria for Patients Assigned to Haploidentical BM Arm:

Patients must be HLA typed at high resolution using DNA based typing at the following

HLA-loci: HLA-A, -B, -C and DRB1 and have available a related haploidentical BM donor

with 2, 3, or 4 HLA-mismatches. A unidirectional mismatch in either the graft versus

host or host versus graft direction is considered a mismatch. The donor and recipient

must be HLA identical for at least one antigen (using high resolution DNA based

typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1. Fulfillment

of this criterion shall be considered sufficient evidence that the donor and

recipient share one HLA haplotype, and typing of additional family members is not

required.

Additional Patient Inclusion Criteria for Patients Assigned to Double Umbilical Cord

Blood Arm:

1. Patients must have available two UCB units fulfilling the following criteria:

1. Each unit must have a minimum of 1.5 x 10^7/kg pre-cryopreserved total

nucleated cell dose. For non-red blood cell depleted units, the minimum

pre-cryopreserved total nucleated cell dose of each unit must be at least

2.0 x10^7/kg.

2. Units must be HLA matched at a minimum of 4/6 to the recipient at HLA -A,

HLA-B (at low resolution using DNA based typing), and HLA -DRB1 (at high

resolution using DNA based typing).

3. Additional graft selection criteria specified in section 2.5

2. Patients must have received at least one cycle of the cytotoxic chemotherapy

regimens (or regimen of similar intensity) listed in Appendix D within 3 months

of enrollment (measured from the start date of chemotherapy) OR have had an

autologous transplant within 24 months of enrollment OR receive 300 cGy as part

of the preparative regimen

Exclusion Criteria:

Patients with suitably matched related or unrelated donor, as defined per

institutional practice.

Recipients of prior autologous hematopoietic stem cell transplantation are ineligible

if disease recurrence occurred less than 6 months from their autologous stem cell

transplant.

Current uncontrolled bacterial, viral or fungal infection (currently taking

medication with evidence of progression of clinical symptoms or radiologic findings).

Prior allogeneic HCT.

Patients with history of primary idiopathic myelofibrosis or any severe marrow

fibrosis.

Planned use of prophylactic donor lymphocyte infusion (DLI) therapy.

Anti-donor HLA antibodies.

Additional exclusion criteria:

Pregnancy or breast-feeding.

Evidence of HIV infection or known HIV positive serology.