Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

NCT01499147 | Completed Results DMC

• 1 other identifier: 2000-0117
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

New conditioning regimens are still needed to maximize efficacy and limit treatment-related deaths of allogeneic transplantation for advanced hematologic malignancies. Over the past several years, the investigators have evaluated several new conditioning regimens that incorporate fludarabine, a novel immunosuppressant that has limited toxicity and that has synergistic activity with alkylating agents. Recent data have suggested that fludarabine may be used in combination with standard doses of oral or IV busulfan, thus reducing the toxicity previously observed with cyclophosphamide/ busulfan regimens.

Conditions

Acute Myeloid Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Malignant Lymphoma; Hodgkin's Disease; Multiple Myeloma; Lymphocytic Leukemia; Myeloproliferative Disorder; Polycythemia Vera; Myelofibrosis; Aplastic Anemia

Keywords

Acute myeloid leukemia; First remission; Acute lymphocytic leukemia; Acute leukemia; Second remission; Early relapse; Partial remission; Accelerated phase; Blast-crisis; Chronic myelogenous leukemia; Chronic phase; Recurrent malignant lymphoma; Refractory malignant lymphoma; Hodgkin's disease; Multiple myeloma.; Chronic lymphocytic leukemia; Myeloproliferative disorder; Polycythemia vera; Myelofibrosis; Severe aplastic anemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Engraftment.

  Median time to ANC engraftment and platelet engraftment in both groups as well as the transfusion requirements measured within 30 days after transplant.

  Up to 30 days post-transplant

Secondary Outcomes (3)

• Participants With 100 Day Transplant-related Mortality.

  Up to 100 days post-transplant.

• Time to ANC and Platelet Engraftment

  Up to 30 days post-transplant

• Number of Participants With Moderate to Severe (Grade 2-4) Acute Graft Versus Host Disease (GVHD).

  Up to 100 days post-transplant (acute GVHD).

Study Arms (2)

Arm 1

ACTIVE COMPARATOR

All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.

Drug: fludarabine/busulfan; Drug: ATG

Arm 2

ACTIVE COMPARATOR

All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.

Drug: fludarabine/ melphalan; Drug: ATG

Interventions

fludarabine/busulfan DRUG

All patients below age 55, should receive fludarabine/busulfan, and ATG in case of unrelated or mismatched donor, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 \<40%, DLCO\<50%, LVEF\<40, Serum bilirubin \>1.5 mg% or serum transaminases \> 2x nl) and/or specific medical conditions such as preventing a standard myeloablative treatment, as per discussion with the PI.

Also known as: Fludarabine:, Fludarabine Phosphate, Fludara, Busulfan:, Busulfex, Myleran

Arm 1

fludarabine/ melphalan DRUG

All patients above age 55 or below age 65, should receive fludarabine/melphalan, and ATG, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 \<40%, DLCO\<50%, LVEF\<40, Serum bilirubin \>1.5 mg% or serum transaminases \> 2x nl).

Also known as: Fludarabine:, Fludarabine phosphate, Fludara, Melphalan:, Alkeran

Arm 2

ATG DRUG

Patients receiving a transplant from a matched unrelated or mismatched related/unrelated donor would receive ATG in the conditioning regimen.

Also known as: Thymoglobulin

Arm 1; Arm 2

Eligibility Criteria

• Age: 10 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with the following diseases:
• Acute myeloid or lymphocytic leukemia in first remission at standard or high-risk for recurrence.
• Acute leukemia in greater than or equal to second remission, or with early relapse, or partial remission.
• Chronic myelogenous leukemia in accelerated phase or blast-crisis.
• Chronic myelogenous leukemia in chronic phase
• Recurrent or refractory malignant lymphoma or Hodgkin's disease
• Multiple myeloma.
• Chronic lymphocytic leukemia, relapsed or with poor prognostic features.
• Myeloproliferative disorder (polycythemia vera, myelofibrosis) with poor prognostic features.
• Severe aplastic anemia after failure of immunosuppressive therapy.
• Age 10-65 years.
• Zubrod performance status less than or equal to 2.
• Adequate cardiac and pulmonary function. Patients with decreased LVEF \< 40% or DLCO \< 50% of predicted will be evaluated by cardiology or pulmonary prior to enrollment on this protocol.
• Patient or guardian able to sign informed consent.

You may not qualify if:

• Life expectancy is severely limited by concomitant illness.
• Serum creatinine greater than 1.5 mg/dL or Creatinine Clearance less than 50 ml/min .
• Serum bilirubin greater than or equal to 2.0 mg/dl, SGPT greater than 3 x upper limit of normal
• Evidence of chronic active hepatitis or cirrhosis
• HIV-positive
• Patient is pregnant

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

University of Illinois at Chicago Medical Center

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma; Hodgkin Disease; Multiple Myeloma; Leukemia, Lymphoid; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis; Anemia, Aplastic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Blast Crisis; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

fludarabine; Busulfan; fludarabine phosphate; Melphalan; thymoglobulin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Anemia; Bone Marrow Failure Disorders; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Leukemia, B-Cell

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Damiano Rondelli, MD
• Organization: University of Illinois Cancer Center

drond@uic.edu

312-996-6179

Study Officials

• Damiano Rondelli, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 23, 2011
• First Posted: December 26, 2011
• Study Start: February 1, 2000
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: November 8, 2018
• Results First Posted: June 14, 2017

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1)