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Reduced-intensity, Related-donor Allogeneic BMT With Fludarabine, Busulfan, and High-dose Posttransplantation Cyclophosphamide for Hematologic Malignancies

Phase 2
6 Months
75 Years
Not Enrolling
Lymphoma, Leukemia, Myelodysplastic Syndrome

Thank you

Trial Information

Reduced-intensity, Related-donor Allogeneic BMT With Fludarabine, Busulfan, and High-dose Posttransplantation Cyclophosphamide for Hematologic Malignancies

At the present time there are few or no cures for people with cancer of the blood or lymph
glands outside of a bone marrow transplant (BMT). BMT has developed over several decades of
research as an effective treatment of various malignant and nonmalignant hematologic

This research is being done to learn more about reduced-intensity bone marrow
transplantation (BMT), also known as a "mini" transplant for patients with blood cancers,
using bone marrow from a relative. The bone marrow for this transplant comes from a relative
who is a half-match or "haplo" match to you. Possible donors include parents, siblings, and

"Mini" transplants have been given to many people with various cancers but are considered
experimental. Over 200 people at Johns Hopkins have received mini transplants with high
doses of cyclophosphamide after the transplant. However, the chemotherapy combination and
other treatment given before those transplants were different from what is in this study.
Although all of the chemotherapy and immune-lowering drugs used in this study are approved
by the Food and Drug Administration (FDA), the combination of medications used in this study
are not FDA approved and are experimental.

Inclusion Criteria:

- First-degree related donor who is at minimum HLA haploidentical

- Eligible diagnoses:

1. Low-grade non-Hodgkin's lymphoma or plasma cell neoplasm that has progressed
during multiagent therapy, failed at least two prior therapies (excluding single
agent rituximab and single agent steroids), or in the case of lymphoma undergone
histological conversion:

- Follicular grade 1 or 2 lymphoma

- Follicular lymphoma not otherwise specified

- Marginal zone (or MALT) lymphoma

- Lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia

- Hairy cell leukemia

- Small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL)

- Prolymphocytic leukemia

- Low grade B-cell lymphoma, unspecified

- Multiple myeloma

- Plasma cell leukemia

2. Poor-risk SLL or CLL, defined by an 11q or 17p deletion, histological
conversion, or disease progression < 6 months after a purine analog-containing

3. Aggressive lymphoma that has failed at least one prior regimen of multiagent
chemotherapy, and patient is either ineligible for autologous BMT or autologous
BMT is not recommended:

- Hodgkin lymphoma

- Follicular grade 3 lymphoma

- Mantle cell lymphoma or leukemia

- Diffuse large B-cell lymphoma (excluding primary CNS lymphoma). Eligible
subtypes include primary mediastinal large B-cell lymphoma, T-cell rich
large B-cell lymphoma, and large B-cell lymphoma not otherwise specified.

- Burkitt's lymphoma/leukemia

- Atypical Burkitt's lymphoma/leukemia (high grade B-cell lymphoma,
unclassified, including that with features intermediate between Burkitt's
and diffuse large B-cell lymphoma)

- Anaplastic large cell lymphoma

- Plasmablastic lymphoma

- Peripheral T-cell lymphoma

4. Relapsed or refractory acute leukemia in second or subsequent remission

5. Poor-risk acute leukemia in first remission

6. AML with at least one of the following:

- AML arising from MDS or a myeloproliferative disorder, or secondary AML

- Presence of Flt3 internal tandem duplications

- Poor-risk cytogenetics

- Primary refractory disease

- ALL (leukemia and/or lymphoma) with at least one of the following:

- Adverse cytogenetics

- Clear evidence of hypodiploidy

- Primary refractory disease

- Biphenotypic leukemia

- MDS with at least one of the following features:

- Poor-risk cytogenetics

- IPSS score of INT-2 or greater

- Treatment-related MDS

- MDS diagnosed before age 21 years

- Progression on or lack of response to standard DNA-methyltransferase
inhibitor therapy

- Life-threatening cytopenias, including those generally requiring
greater than weekly transfusions

7. Interferon- or imatinib-refractory CML in first chronic phase, or non-blast
crisis CML beyond first chronic phase

8. Philadelphia chromosome negative myeloproliferative disease (including

9. Chronic myelomonocytic leukemia

10. Juvenile myelomonocytic leukemia

- For patients with SLL, CLL, or prolymphocytic leukemia, < 20% of bone
marrow cellularity involved by this process

- Adequate end-organ function:

- Left ventricular ejection fraction greater than or equal to 35%

- Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and
AST < 5 x ULN

- FEV1 and FVC > 40% of predicted; or in pediatric patients, if unable to perform
pulmonary function tests due to young age, oxygen saturation >92% on room air

- ECOG performance status < 2 or Karnofsky or Lansky score > 60

Exclusion Criteria:

- Pregnant or breast-feeding

- Uncontrolled infection Note: Infection is permitted if there is evidence of response
to medication. Eligibility of HIV infected patients will be determined on a
case-by-case basis.

- Any previous BMT within 3 months prior to start of conditioning

- Active extra-medullary leukemia or known active Central Nervous System (CNS)
involvement by malignancy. Such disease treated into remission is permitted.

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Estimate the proportion of patients achieving full donor chimerism

Outcome Description:

After reduced-intensity, partially (Human leukocyte antigen) HLA-mismatched or HLA-matched BMT with fludarabine, busulfan, and post-grafting immunosuppression that includes high-dose cyclophosphamide, estimate the proportion achieving full donor chimerism by Day 60 in unsorted and CD3+ sorted peripheral blood.

Outcome Time Frame:

Day 60

Safety Issue:


Principal Investigator

Yvette Kasamon, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Johns Hopkins University


United States: Institutional Review Board

Study ID:




Start Date:

August 2010

Completion Date:

May 2012

Related Keywords:

  • Lymphoma
  • Leukemia
  • Myelodysplastic Syndrome
  • Lymphoma
  • Hodgkin's lymphoma
  • Non hodgkin's lymphoma
  • Leukemia
  • Acute myeloid leukemia (AML)
  • Acute lymphoblastic leukemia(ALL)
  • Chronic myeloid leukemia (CML)
  • Chronic Myelomonocytic (CMML)
  • Myelodysplastic syndrome (MDS)
  • High-risk acute leukemia in first remission
  • Relapsed leukemia in remission
  • Cyclophosphamide
  • High-dose cyclophosphamide
  • Fludarabine
  • Busulfan
  • Allogeneic
  • Nonmyeloablative
  • Reduced intensity
  • Haploidentical
  • Bone marrow transplant (BMT)
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Preleukemia



The Sydney Kimmel Comprehensive Cancer center Baltimore, Maryland  21231